Orthocoronavirinae ist eine Virusunterfamilie innerhalb der Familie Coronaviridae, die weitestgehend mit dieser übereinstimmt. Die Viren innerhalb dieser Unterfamilie werden (fach)umgangssprachlich Orthocoronaviren und veraltet und zweideutig auch bloß Coronaviren genannt.
Auch alle Coronaviren, die den Menschen infizieren, gehören zu den Orthocoronaviren. Darunter auch SARS-CoV-2, das Virus, das für die aktuelle COVID-19-Pandemie verantwortlich ist.
Bis heute (Stand 2020) entspricht die Beschreibung der Unterfamilie Orthocoronavirinae nahezu vollständig der der übergeordneten Familie Coronaviridae. Das liegt daran, dass die einzige Schwestergruppe – die Unterfamilie der Letoviren (Letovirinae) – nur wenig erforscht ist und nur eine einzige Art – Microhyla letovirus 1 – enthält. Neben strukturellen und statistischen Unterschieden im Virusgenom bei computergestützten Analysen (vgl. Bioinformatik) besteht der wesentlichste Unterschied zwischen den beiden Unterfamilien Orthocoronavirinae und Letovirinae vor allem darin, dass die Letoviren die ersten Coronaviren sind, die Amphibien infizieren.[2][3]
Der Name der Unterfamilie Orthocoronavirinae setzt sich aus dem Vorsatz „Ortho-“ (griechisch ὀρθός orthós, deutsch ‚recht, richtig, aufrecht‘) und dem früheren Namen dieser Unterfamilie Coronavirinae zusammen. „Orthocoronaviren“ bedeutet soviel wie: „richtige, eigentliche, klassische oder echte Coronaviren“. Das entspricht der zuvor gebrauchten umgangssprachlichen Bezeichnung: „echte Coronaviren“ (englisch true coronaviruses[4]), für die Viren dieser Gruppe bevor die Gruppe den jetzigen Namen erhielt.
Diese Virengruppe wurde zunächst als Gattung unter dem Namen Coronavirus geführt (bis 2008). Durch den Aufstieg in den Rang einer Unterfamilie wurde die Endung in „-virinae“ geändert.[4] Die Herkunft des Namensbestandteils „corona“ wird genauer im Abschnitt Etymologie im Artikel zur Familie Coronaviridae erläutert.
Die Namenserweiterung „Ortho-“ beendete 2018 gewisse Mehrdeutigkeiten, die innerhalb der Familie Coronaviridae aufgrund dessen bestanden, dass der gleiche Wortstamm „Corona-“ für mehrere ineinanderliegende Gruppen verwendet worden war.[5] Näheres unter Taxonomische Hintergründe.
Aus dem Taxonnamen Orthocoronavirinae ergibt sich systematisch die Sammelbezeichnung (englisch collective name[6]) „Orthocoronaviren“ für Viren dieser Unterfamilie.[7][8] Besonders im Englischen wird diese Art der Sammelbezeichnung auch „Vernakularname“ (englisch vernacular name) genannt.[5]
Die Sammelbezeichnung „Orthocoronaviren“ ist noch verhältnismäßig jung im Vergleich zum seit den 1960er Jahren gebrauchten Namen „Coronaviren“.[9] Obwohl der ältere Name „Coronaviren“ zweideutig sowohl die Viren der ganzen Familie[10] als auch nur der Unterfamilie (früher: Gattung[4]) bezeichnet, ist er weiter auch für nur die Viren der Unterfamilie im Gebrauch.[11][12][13][14][15]
Aus diesen Gründen existieren grundsätzlich immer noch zwei Vernakularnamen für die Viren dieser Gruppe. Einmal der doppeldeutige Name „Coronaviren“ (englisch coronaviruses). Dieser findet sich in Literatur bis 2018[16] und häufig auch noch nach 2018. Und dann der eindeutige Name „Orthocoronaviren“ als taxonomische Sammelbezeichnung seit 2018. Der eigentlich korrekte und eindeutige englische Vernakularname "coronavirids" findet allerdings auch heute noch nur gelegentlich Verwendung,[17] dieser ist analog der Bezeichnung nanovirids des ICTV[18] für die Familie Nanoviridae, sowie hominids bzw. camelids[19] für die Familien der Hominiden respektive Cameliden gebildet.[Anm. 1]
Wegen der Namensähnlichkeit zwischen Familie und Unterfamilie kommt es allenthalben auch zur Falschschreibung des Unterfamiliennamens in der Form: Orthocoronaviridae.[20]
Die Unterfamilie Orthocoronavirinae besitzt aktuell nur eine Schwester-Unterfamilie in der Familie Coronaviridae. Diese heißt Letovirinae und ersetzte 2018 die damalige Schwester-Unterfamilie Torovirinae (heute Familie Tobaniviridae mit der neuen(!) Unterfamilie Torovirinae).[2]
Auszug aus der systematischen Darstellung nach ICTV. Eine ausführlichere Darstellung findet sich im Artikel über die Familie Coronaviridae im Abschnitt über die innere Systematik.
Die taxonomische Benennung und Einordnung der Orthocoronaviren fand immer vor dem Hintergrund der taxonomischen Gesamtorganisation der Virenfamilie Coronaviridae statt und kann dort nachgelesen werden.
Orthocoronavirinae ist eine Virusunterfamilie innerhalb der Familie Coronaviridae, die weitestgehend mit dieser übereinstimmt. Die Viren innerhalb dieser Unterfamilie werden (fach)umgangssprachlich Orthocoronaviren und veraltet und zweideutig auch bloß Coronaviren genannt.
Auch alle Coronaviren, die den Menschen infizieren, gehören zu den Orthocoronaviren. Darunter auch SARS-CoV-2, das Virus, das für die aktuelle COVID-19-Pandemie verantwortlich ist.
Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS and COVID-19, which is causing the ongoing pandemic. In cows and pigs they cause diarrhea, while in mice they cause hepatitis and encephalomyelitis.
Coronaviruses constitute the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales and realm Riboviria.[3][4] They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry.[5] The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses.[6] They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of the stellar corona, from which their name derives.[7]
The name "coronavirus" is derived from Latin corona, meaning "crown" or "wreath", itself a borrowing from Greek κορώνη korṓnē, "garland, wreath".[8][9] The name was coined by June Almeida and David Tyrrell who first observed and studied human coronaviruses.[10] The word was first used in print in 1968 by an informal group of virologists in the journal Nature to designate the new family of viruses.[7] The name refers to the characteristic appearance of virions (the infective form of the virus) by electron microscopy, which have a fringe of large, bulbous surface projections creating an image reminiscent of the solar corona or halo.[7][10] This morphology is created by the viral spike peplomers, which are proteins on the surface of the virus.[11]
The scientific name Coronavirus was accepted as a genus name by the International Committee for the Nomenclature of Viruses (later renamed International Committee on Taxonomy of Viruses) in 1971.[12] As the number of new species increased, the genus was split into four genera, namely Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus in 2009.[13] The common name coronavirus is used to refer to any member of the subfamily Orthocoronavirinae.[4] As of 2020, 45 species are officially recognised.[14]
The earliest reports of a coronavirus infection in animals occurred in the late 1920s, when an acute respiratory infection of domesticated chickens emerged in North America.[15] Arthur Schalk and M.C. Hawn in 1931 made the first detailed report which described a new respiratory infection of chickens in North Dakota. The infection of new-born chicks was characterized by gasping and listlessness with high mortality rates of 40–90%.[16] Leland David Bushnell and Carl Alfred Brandly isolated the virus that caused the infection in 1933.[17] The virus was then known as infectious bronchitis virus (IBV). Charles D. Hudson and Fred Robert Beaudette cultivated the virus for the first time in 1937.[18] The specimen came to be known as the Beaudette strain. In the late 1940s, two more animal coronaviruses, JHM that causes brain disease (murine encephalitis) and mouse hepatitis virus (MHV) that causes hepatitis in mice were discovered.[19] It was not realized at the time that these three different viruses were related.[20][12]
Human coronaviruses were discovered in the 1960s[21][22] using two different methods in the United Kingdom and the United States.[23] E.C. Kendall, Malcolm Bynoe, and David Tyrrell working at the Common Cold Unit of the British Medical Research Council collected a unique common cold virus designated B814 in 1961.[24][25][26] The virus could not be cultivated using standard techniques which had successfully cultivated rhinoviruses, adenoviruses and other known common cold viruses. In 1965, Tyrrell and Bynoe successfully cultivated the novel virus by serially passing it through organ culture of human embryonic trachea.[27] The new cultivating method was introduced to the lab by Bertil Hoorn.[28] The isolated virus when intranasally inoculated into volunteers caused a cold and was inactivated by ether which indicated it had a lipid envelope.[24][29] Dorothy Hamre[30] and John Procknow at the University of Chicago isolated a novel cold from medical students in 1962. They isolated and grew the virus in kidney tissue culture, designating it 229E. The novel virus caused a cold in volunteers and, like B814, was inactivated by ether.[31]
Scottish virologist June Almeida at St Thomas' Hospital in London, collaborating with Tyrrell, compared the structures of IBV, B814 and 229E in 1967.[32][33] Using electron microscopy the three viruses were shown to be morphologically related by their general shape and distinctive club-like spikes.[34] A research group at the National Institute of Health the same year was able to isolate another member of this new group of viruses using organ culture and named one of the samples OC43 (OC for organ culture).[35] Like B814, 229E, and IBV, the novel cold virus OC43 had distinctive club-like spikes when observed with the electron microscope.[36][37]
The IBV-like novel cold viruses were soon shown to be also morphologically related to the mouse hepatitis virus.[19] This new group of viruses were named coronaviruses after their distinctive morphological appearance.[7] Human coronavirus 229E and human coronavirus OC43 continued to be studied in subsequent decades.[38][39] The coronavirus strain B814 was lost. It is not known which present human coronavirus it was.[40] Other human coronaviruses have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2003, HCoV HKU1 in 2004, MERS-CoV in 2013, and SARS-CoV-2 in 2019.[41] There have also been a large number of animal coronaviruses identified since the 1960s.[42]
Coronaviruses are large, roughly spherical particles with unique surface projections.[43] Their size is highly variable with average diameters of 80 to 120 nm. Extreme sizes are known from 50 to 200 nm in diameter.[44] The total molecular mass is on average 40,000 kDa. They are enclosed in an envelope embedded with a number of protein molecules.[45] The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell.[46]
The viral envelope is made up of a lipid bilayer in which the membrane (M), envelope (E) and spike (S) structural proteins are anchored.[47] The molar ratio of E:S:M in the lipid bilayer is approximately 1:20:300.[48] The E and M protein are the structural proteins that combined with the lipid bilayer to shape the viral envelope and maintain its size.[49] S proteins are needed for interaction with the host cells. But human coronavirus NL63 is peculiar in that its M protein has the binding site for the host cell, and not its S protein.[50] The diameter of the envelope is 85 nm. The envelope of the virus in electron micrographs appears as a distinct pair of electron-dense shells (shells that are relatively opaque to the electron beam used to scan the virus particle).[51][49]
The M protein is the main structural protein of the envelope that provides the overall shape and is a type III membrane protein. It consists of 218 to 263 Amino acid residues and forms a layer 7.8 nm thick.[45] It has three domains, a short N-terminal ectodomain, a triple-spanning transmembrane domain, and a C-terminal endodomain. The C-terminal domain forms a matrix-like lattice that adds to the extra-thickness of the envelope. Different species can have either N- or O-linked glycans in their protein amino-terminal domain. The M protein is crucial during the assembly, budding, envelope formation, and pathogenesis stages of the virus lifecycle.[52]
The E proteins are minor structural proteins and highly variable in different species.[44] There are only about 20 copies of the E protein molecule in a coronavirus particle.[48] They are 8.4 to 12 kDa in size and are composed of 76 to 109 amino acids.[44] They are integral proteins (i.e. embedded in the lipid layer) and have two domains namely a transmembrane domain and an extramembrane C-terminal domain. They are almost fully α-helical, with a single α-helical transmembrane domain, and form pentameric (five-molecular) ion channels in the lipid bilayer. They are responsible for virion assembly, intracellular trafficking and morphogenesis (budding).[45]
The spikes are the most distinguishing feature of coronaviruses and are responsible for the corona- or halo-like surface. On average a coronavirus particle has 74 surface spikes.[53] Each spike is about 20 nm long and is composed of a trimer of the S protein. The S protein is in turn composed of an S1 and S2 subunit. The homotrimeric S protein is a class I fusion protein which mediates the receptor binding and membrane fusion between the virus and host cell. The S1 subunit forms the head of the spike and has the receptor-binding domain (RBD). The S2 subunit forms the stem which anchors the spike in the viral envelope and on protease activation enables fusion. The two subunits remain noncovalently linked as they are exposed on the viral surface until they attach to the host cell membrane.[45] In a functionally active state, three S1 are attached to two S2 subunits. The subunit complex is split into individual subunits when the virus binds and fuses with the host cell under the action of proteases such as cathepsin family and transmembrane protease serine 2 (TMPRSS2) of the host cell.[54]
S1 proteins are the most critical components in terms of infection. They are also the most variable components as they are responsible for host cell specificity. They possess two major domains named N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), both of which serve as the receptor-binding domains. The NTDs recognize and bind sugars on the surface of the host cell. An exception is the MHV NTD that binds to a protein receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). S1-CTDs are responsible for recognizing different protein receptors such as angiotensin-converting enzyme 2 (ACE2), aminopeptidase N (APN), and dipeptidyl peptidase 4 (DPP4).[45]
A subset of coronaviruses (specifically the members of betacoronavirus subgroup A) also has a shorter spike-like surface protein called hemagglutinin esterase (HE).[42] The HE proteins occur as homodimers composed of about 400 amino acid residues and are 40 to 50 kDa in size. They appear as tiny surface projections of 5 to 7 nm long embedded in between the spikes. They help in the attachment to and detachment from the host cell.[55]
Inside the envelope, there is the nucleocapsid, which is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-stranded RNA genome in a continuous beads-on-a-string type conformation.[49][56] N protein is a phosphoprotein of 43 to 50 kDa in size, and is divided into three conserved domains. The majority of the protein is made up of domains 1 and 2, which are typically rich in arginines and lysines. Domain 3 has a short carboxy terminal end and has a net negative charge due to excess of acidic over basic amino acid residues.[44]
Coronaviruses contain a positive-sense, single-stranded RNA genome. The genome size for coronaviruses ranges from 26.4 to 31.7 kilobases.[6] The genome size is one of the largest among RNA viruses. The genome has a 5′ methylated cap and a 3′ polyadenylated tail.[49]
The genome organization for a coronavirus is 5′-leader-UTR-replicase (ORF1ab)-spike (S)-envelope (E)-membrane (M)-nucleocapsid (N)-3′UTR-poly (A) tail. The open reading frames 1a and 1b, which occupy the first two-thirds of the genome, encode the replicase polyprotein (pp1ab). The replicase polyprotein self cleaves to form 16 nonstructural proteins (nsp1–nsp16).[49]
The later reading frames encode the four major structural proteins: spike, envelope, membrane, and nucleocapsid.[57] Interspersed between these reading frames are the reading frames for the accessory proteins. The number of accessory proteins and their function is unique depending on the specific coronavirus.[49]
Infection begins when the viral spike protein attaches to its complementary host cell receptor. After attachment, a protease of the host cell cleaves and activates the receptor-attached spike protein. Depending on the host cell protease available, cleavage and activation allows the virus to enter the host cell by endocytosis or direct fusion of the viral envelope with the host membrane.[58]
Coronaviruses can enter cells by either fusing to their lipid envelope with the cell membrane on the cell surface or by internalization via endocytosis.[59]
On entry into the host cell, the virus particle is uncoated, and its genome enters the cell cytoplasm. The coronavirus RNA genome has a 5′ methylated cap and a 3′ polyadenylated tail, which allows it to act like a messenger RNA and be directly translated by the host cell's ribosomes. The host ribosomes translate the initial overlapping open reading frames ORF1a and ORF1b of the virus genome into two large overlapping polyproteins, pp1a and pp1ab.[49]
The larger polyprotein pp1ab is a result of a -1 ribosomal frameshift caused by a slippery sequence (UUUAAAC) and a downstream RNA pseudoknot at the end of open reading frame ORF1a.[60] The ribosomal frameshift allows for the continuous translation of ORF1a followed by ORF1b.[49]
The polyproteins have their own proteases, PLpro (nsp3) and 3CLpro (nsp5), which cleave the polyproteins at different specific sites. The cleavage of polyprotein pp1ab yields 16 nonstructural proteins (nsp1 to nsp16). Product proteins include various replication proteins such as RNA-dependent RNA polymerase (nsp12), RNA helicase (nsp13), and exoribonuclease (nsp14).[49]
A number of the nonstructural proteins coalesce to form a multi-protein replicase-transcriptase complex (RTC). The main replicase-transcriptase protein is the RNA-dependent RNA polymerase (RdRp). It is directly involved in the replication and transcription of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process. The exoribonuclease nonstructural protein, for instance, provides extra fidelity to replication by providing a proofreading function which the RNA-dependent RNA polymerase lacks.[61]
Replication – One of the main functions of the complex is to replicate the viral genome. RdRp directly mediates the synthesis of negative-sense genomic RNA from the positive-sense genomic RNA. This is followed by the replication of positive-sense genomic RNA from the negative-sense genomic RNA.[49]
Transcription – The other important function of the complex is to transcribe the viral genome. RdRp directly mediates the synthesis of negative-sense subgenomic RNA molecules from the positive-sense genomic RNA. This process is followed by the transcription of these negative-sense subgenomic RNA molecules to their corresponding positive-sense mRNAs.[49] The subgenomic mRNAs form a "nested set" which have a common 5'-head and partially duplicate 3'-end.[62]
Recombination – The replicase-transcriptase complex is also capable of genetic recombination when at least two viral genomes are present in the same infected cell.[62] RNA recombination appears to be a major driving force in determining genetic variability within a coronavirus species, the capability of a coronavirus species to jump from one host to another and, infrequently, in determining the emergence of novel coronaviruses.[63] The exact mechanism of recombination in coronaviruses is unclear, but likely involves template switching during genome replication.[63]
The replicated positive-sense genomic RNA becomes the genome of the progeny viruses. The mRNAs are gene transcripts of the last third of the virus genome after the initial overlapping reading frame. These mRNAs are translated by the host's ribosomes into the structural proteins and many accessory proteins.[49] RNA translation occurs inside the endoplasmic reticulum. The viral structural proteins S, E, and M move along the secretory pathway into the Golgi intermediate compartment. There, the M proteins direct most protein-protein interactions required for the assembly of viruses following its binding to the nucleocapsid. Progeny viruses are then released from the host cell by exocytosis through secretory vesicles. Once released the viruses can infect other host cells.[64]
Infected carriers are able to shed viruses into the environment. The interaction of the coronavirus spike protein with its complementary cell receptor is central in determining the tissue tropism, infectivity, and species range of the released virus.[65][66] Coronaviruses mainly target epithelial cells.[42] They are transmitted from one host to another host, depending on the coronavirus species, by either an aerosol, fomite, or fecal-oral route.[67]
Human coronaviruses infect the epithelial cells of the respiratory tract, while animal coronaviruses generally infect the epithelial cells of the digestive tract.[42] SARS coronavirus, for example, infects the human epithelial cells of the lungs via an aerosol route[68] by binding to the angiotensin-converting enzyme 2 (ACE2) receptor.[69] Transmissible gastroenteritis coronavirus (TGEV) infects the pig epithelial cells of the digestive tract via a fecal-oral route[67] by binding to the Alanine aminopeptidase (APN) receptor.[49]
Coronaviruses form the subfamily Orthocoronavirinae,[2][3][4] which is one of two sub-families in the family Coronaviridae, order Nidovirales, and realm Riboviria.[42][70] They are divided into the four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus. Alphacoronaviruses and betacoronaviruses infect mammals, while gammacoronaviruses and deltacoronaviruses primarily infect birds.[71][72]
The most recent common ancestor (MRCA) of all coronaviruses is estimated to have existed as recently as 8000 BCE, although some models place the common ancestor as far back as 55 million years or more, implying long term coevolution with bat and avian species.[73] The most recent common ancestor of the alphacoronavirus line has been placed at about 2400 BCE, of the betacoronavirus line at 3300 BCE, of the gammacoronavirus line at 2800 BCE, and the deltacoronavirus line at about 3000 BCE. Bats and birds, as warm-blooded flying vertebrates, are an ideal natural reservoir for the coronavirus gene pool (with bats the reservoir for alphacoronaviruses and betacoronavirus – and birds the reservoir for gammacoronaviruses and deltacoronaviruses). The large number and global range of bat and avian species that host viruses have enabled extensive evolution and dissemination of coronaviruses.[74]
Many human coronaviruses have their origin in bats.[75] The human coronavirus NL63 shared a common ancestor with a bat coronavirus (ARCoV.2) between 1190 and 1449 CE.[76] The human coronavirus 229E shared a common ancestor with a bat coronavirus (GhanaGrp1 Bt CoV) between 1686 and 1800 CE.[77] More recently, alpaca coronavirus and human coronavirus 229E diverged sometime before 1960.[78] MERS-CoV emerged in humans from bats through the intermediate host of camels.[79] MERS-CoV, although related to several bat coronavirus species, appears to have diverged from these several centuries ago.[80] The most closely related bat coronavirus and SARS-CoV diverged in 1986.[81] The ancestors of SARS-CoV first infected leaf-nose bats of the genus Hipposideridae; subsequently, they spread to horseshoe bats in the species Rhinolophidae, then to Asian palm civets, and finally to humans.[82][83]
Unlike other betacoronaviruses, bovine coronavirus of the species Betacoronavirus 1 and subgenus Embecovirus is thought to have originated in rodents and not in bats.[75][84] In the 1790s, equine coronavirus diverged from the bovine coronavirus after a cross-species jump.[85] Later in the 1890s, human coronavirus OC43 diverged from bovine coronavirus after another cross-species spillover event.[86][85] It is speculated that the flu pandemic of 1890 may have been caused by this spillover event, and not by the influenza virus, because of the related timing, neurological symptoms, and unknown causative agent of the pandemic.[87] Besides causing respiratory infections, human coronavirus OC43 is also suspected of playing a role in neurological diseases.[88] In the 1950s, the human coronavirus OC43 began to diverge into its present genotypes.[89] Phylogenetically, mouse hepatitis virus (Murine coronavirus), which infects the mouse's liver and central nervous system,[90] is related to human coronavirus OC43 and bovine coronavirus. Human coronavirus HKU1, like the aforementioned viruses, also has its origins in rodents.[75]
Coronaviruses vary significantly in risk factor. Some can kill more than 30% of those infected, such as MERS-CoV, and some are relatively harmless, such as the common cold.[49] Coronaviruses can cause colds with major symptoms, such as fever, and a sore throat from swollen adenoids.[91] Coronaviruses can cause pneumonia (either direct viral pneumonia or secondary bacterial pneumonia) and bronchitis (either direct viral bronchitis or secondary bacterial bronchitis).[92] The human coronavirus discovered in 2003, SARS-CoV, which causes severe acute respiratory syndrome (SARS), has a unique pathogenesis because it causes both upper and lower respiratory tract infections.[92]
Six species of human coronaviruses are known, with one species subdivided into two different strains, making seven strains of human coronaviruses altogether.
Four human coronaviruses produce symptoms that are generally mild, even though it is contended they might have been more aggressive in the past:[93]
Three human coronaviruses produce potentially severe symptoms:
These cause the diseases commonly called SARS, MERS, and COVID-19 respectively.
Although the common cold is usually caused by rhinoviruses,[94] in about 15% of cases the cause is a coronavirus.[95] The human coronaviruses HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63 continually circulate in the human population in adults and children worldwide and produce the generally mild symptoms of the common cold.[88] The four mild coronaviruses have a seasonal incidence occurring in the winter months in temperate climates.[96][97] There is no preponderance in any season in tropical climates.[98]
In 2003, following the outbreak of severe acute respiratory syndrome (SARS) which had begun the prior year in Asia, and secondary cases elsewhere in the world, the World Health Organization (WHO) issued a press release stating that a novel coronavirus identified by several laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV). More than 8,000 people from 29 countries and territories were infected, and at least 774 died.[108][69]
In September 2012, a new type of coronavirus was identified, initially called Novel Coronavirus 2012, and now officially named Middle East respiratory syndrome coronavirus (MERS-CoV).[109][110] The World Health Organization issued a global alert soon after.[111] The WHO update on 28 September 2012 said the virus did not seem to pass easily from person to person.[112] However, on 12 May 2013, a case of human-to-human transmission in France was confirmed by the French Ministry of Social Affairs and Health.[113] In addition, cases of human-to-human transmission were reported by the Ministry of Health in Tunisia. Two confirmed cases involved people who seemed to have caught the disease from their late father, who became ill after a visit to Qatar and Saudi Arabia. Despite this, it appears the virus had trouble spreading from human to human, as most individuals who are infected do not transmit the virus.[114] By 30 October 2013, there were 124 cases and 52 deaths in Saudi Arabia.[115]
After the Dutch Erasmus Medical Centre sequenced the virus, the virus was given a new name, Human Coronavirus–Erasmus Medical Centre (HCoV-EMC). The final name for the virus is Middle East respiratory syndrome coronavirus (MERS-CoV). The only U.S. cases (both survived) were recorded in May 2014.[116]
In May 2015, an outbreak of MERS-CoV occurred in the Republic of Korea, when a man who had traveled to the Middle East, visited four hospitals in the Seoul area to treat his illness. This caused one of the largest outbreaks of MERS-CoV outside the Middle East.[117] As of December 2019, 2,468 cases of MERS-CoV infection had been confirmed by laboratory tests, 851 of which were fatal, a mortality rate of approximately 34.5%.[118]
In December 2019, a pneumonia outbreak was reported in Wuhan, China.[119] On 31 December 2019, the outbreak was traced to a novel strain of coronavirus,[120] which was given the interim name 2019-nCoV by the World Health Organization,[121][122][123] later renamed SARS-CoV-2 by the International Committee on Taxonomy of Viruses.
As of 10 March 2023, there have been at least 6,881,955[104] confirmed deaths and more than 676,609,955[104] confirmed cases in the COVID-19 pandemic. The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with approximately 70% genetic similarity to the SARS-CoV.[124] The virus has a 96% similarity to a bat coronavirus, so it is widely suspected to originate from bats as well.[125][126]
During a surveillance study of archived samples of Malaysian viral pneumonia patients, virologists identified a strain of canine coronavirus which has infected humans in 2018.
Coronaviruses have been recognized as causing pathological conditions in veterinary medicine since the 1930s.[19] They infect a range of animals including swine, cattle, horses, camels, cats, dogs, rodents, birds and bats.[127] The majority of animal related coronaviruses infect the intestinal tract and are transmitted by a fecal-oral route.[128] Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.[129]
Coronaviruses infect domesticated birds.[130] Infectious bronchitis virus (IBV), a type of coronavirus, causes avian infectious bronchitis.[131] The virus is of concern to the poultry industry because of the high mortality from infection, its rapid spread, and its effect on production.[127] The virus affects both meat production and egg production and causes substantial economic loss.[132] In chickens, infectious bronchitis virus targets not only the respiratory tract but also the urogenital tract. The virus can spread to different organs throughout the chicken.[131] The virus is transmitted by aerosol and food contaminated by feces. Different vaccines against IBV exist and have helped to limit the spread of the virus and its variants.[127] Infectious bronchitis virus is one of a number of strains of the species Avian coronavirus.[133] Another strain of avian coronavirus is turkey coronavirus (TCV) which causes enteritis in turkeys.[127]
Coronaviruses also affect other branches of animal husbandry such as pig farming and the Cattle raising.[127] Swine acute diarrhea syndrome coronavirus (SADS-CoV), which is related to bat coronavirus HKU2, causes diarrhea in pigs.[134] Porcine epidemic diarrhea virus (PEDV) is a coronavirus that has recently emerged and similarly causes diarrhea in pigs.[135] Transmissible gastroenteritis virus (TGEV), which is a member of the species Alphacoronavirus 1,[136] is another coronavirus that causes diarrhea in young pigs.[137][138] In the cattle industry bovine coronavirus (BCV), which is a member of the species Betacoronavirus 1 and related to HCoV-OC43,[139] is responsible for severe profuse enteritis in young calves.[127]
Coronaviruses infect domestic pets such as cats, dogs, and ferrets.[130] There are two forms of feline coronavirus which are both members of the species Alphacoronavirus 1.[136] Feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline infectious peritonitis (FIP), a disease with high mortality.[127] There are two different coronaviruses that infect dogs. Canine coronavirus (CCoV), which is a member of the species Alphacoronavirus 1,[136] causes mild gastrointestinal disease.[127] Canine respiratory coronavirus (CRCoV), which is a member of the species Betacoronavirus 1 and related to HCoV-OC43,[139] cause respiratory disease.[127] Similarly, there are two types of coronavirus that infect ferrets.[140] Ferret enteric coronavirus causes a gastrointestinal syndrome known as epizootic catarrhal enteritis (ECE), and a more lethal systemic version of the virus (like FIP in cats) known as ferret systemic coronavirus (FSC).[141][142]
Coronaviruses infect laboratory animals.[127] Mouse hepatitis virus (MHV), which is a member of the species Murine coronavirus,[143] causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice.[144] Prior to the discovery of SARS-CoV, MHV was the best-studied coronavirus both in vivo and in vitro as well as at the molecular level. Some strains of MHV cause a progressive demyelinating encephalitis in mice which has been used as a murine model for multiple sclerosis.[129] Sialodacryoadenitis virus (SDAV), which is a strain of the species Murine coronavirus,[143] is highly infectious coronavirus of laboratory rats, which can be transmitted between individuals by direct contact and indirectly by aerosol. Rabbit enteric coronavirus causes acute gastrointestinal disease and diarrhea in young European rabbits.[127] Mortality rates are high.[145]
A number of vaccines using different methods have been developed against human coronavirus SARS-CoV-2.[146][147] Antiviral targets against human coronaviruses have also been identified such as viral proteases, polymerases, and entry proteins. Drugs are in development which target these proteins and the different steps of viral replication.[148][147]
Vaccines are available for animal coronaviruses IBV, TGEV, and Canine CoV, although their effectiveness is limited. In the case of outbreaks of highly contagious animal coronaviruses, such as PEDV, measures such as destruction of entire herds of pigs may be used to prevent transmission to other herds.[49]
Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS and COVID-19, which is causing the ongoing pandemic. In cows and pigs they cause diarrhea, while in mice they cause hepatitis and encephalomyelitis.
Coronaviruses constitute the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales and realm Riboviria. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses. They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of the stellar corona, from which their name derives.
Orthocoronavirinae, comúnmente conocidos como coronavirus, es una subfamilia de virus ARN monocatenario positivos perteneciente a la familia Coronaviridae. Se subdivide en los géneros Alphacoronavirus, Betacoronavirus, Gammacoronavirus y Deltacoronavirus.[2][3] Estos incluyen genogrupos filogenéticamente similares de virus con una nucleocápside de simetría helicoidal con envoltura cuyos viriones pueden medir entre aproximadamente 50 y 200 nm de diámetro. Su material genético es el de mayor tamaño dentro de los virus de ARN, con genomas que van desde los 26 a 32 kilonucleótidos.[4][5] Se les llama coronavirus por la corona de puntas que se ve alrededor de la superficie del virus. Fue descrito por primera vez en 1965.[6]
Los coronavirus pueden infectar aves y mamíferos produciendo una serie de enfermedades respiratorias y digestivas, muchas de ellas letales trayendo como consecuencia serios perjuicios en la avicultura y la ganadería; también pueden infectar al ser humano causando enfermedades que van desde el resfriado común hasta enfermedades más graves, como bronquitis, bronquiolitis, neumonía, el síndrome respiratorio de Oriente Medio (MERS), el síndrome respiratorio agudo grave (SARS) y el COVID-19, entre otras. La mayoría de las personas se infectan con estos virus en algún momento de su vida.[2][7][3][8]
Hasta la fecha se han registrado cuarenta y cinco especies de coronavirus.[1] Varias especies son de reciente investigación[8] debido a que varias cepas particulares no habían sido identificadas previamente en humanos.[9] Existe poca información sobre la transmisión, gravedad e impacto clínico[9] y no existen tratamientos aprobados hasta la fecha,[8] sin embargo se pueden tratar varios de los síntomas, las opciones terapéuticas dependen del estado clínico de cada paciente.[8]
El género Alphacoronavirus —anteriormente conocido como Coronavirus grupo 1 (CoV-1)— incluye los subgrupos 1a y 1b, cuyos integrantes más representativos son el coronavirus humano 229E (HCoV-229E) y HCoV-NL63, así como la nueva especie alfacoronavirus 1 —incluyendo virus de la gastroenteritis transmisible porcina (TGEV)—, respectivamente. El género Betacoronavirus —anteriormente Betacoronavirus grupo 2 (Cov-2)— incluye varios subgrupos. Los más prominentes (subgrupos 2a y 2b) tienen como especies tipo las especies de coronavirus murino —incluido el virus de la hepatitis de ratón (MHV)– y el SARS-CoV, respectivamente. Los géneros Alphacoronavirus y Betacoronavirus provienen del pool genético que tiene a murciélagos como huésped. El género Gammacoronavirus incluye todos los coronavirus aviares identificados hasta 2009.[10][11]
El ancestro común más reciente del coronavirus se ha encontrado en el siglo IX a. C. Estudios realizados durante 1990 lograron datar los ancestros comunes más recientes de los géneros:
De acuerdo a estos estudios, en ese entonces el factor principal de la fuente del coronavirus era la sangre caliente, particularmente de los murciélagos y pájaros. El coronavirus bovino se separó de la especie equina coronavirus al final del siglo XVIII. El coronavirus bovino y el coronavirus humano OC43 se separaron en 1899. Otra estimación sugiere que el coronavirus humano OC43 divergió del coronavirus bovino en 1890. El coronavirus bovino y el canino respiratorio con el coronavirus divergieron de un ancestro común en 1951. El ancestro común más reciente del coronavirus humano OC43 ha sido fechado en la década de 1950. El síndrome respiratorio coronavirus de Oriente Medio, aunque relacionado con varias especies de murciélagos, parece haber divergido de estos hace varios siglos. El coronavirus de murciélago está más estrechamente relacionado con el coronavirus del SARS, del que se separó en 1986.[12][13][14][15][16][17][18][19][20][21][22]
Las partes que conforman la estructura general de los coronavirus son, como en todos los virus animales, la envoltura y la nucleocápside. En el caso de los coronavirus, en la envoltura se encuentra una glucoproteína de membrana (M) de 20 a 35 kDa, que forma una matriz en contacto con la nucleocápside. Además se encuentra en la envoltura la glucoproteína S, de 180 a 220 kDa,[23] que forma las espículas, espigas o peplómeros responsables de la adhesión a la célula huésped. En el caso específico del coronavirus SARS, en sus espículas un dominio de unión para receptores definidos dirigen la adherencia del virus a su receptor celular, la enzima convertidora de angiotensina 2 (ACE-2).[24] Algunos coronavirus (específicamente los miembros de Betacoronavirus subgrupo A, también llamado subgénero Embecovirus[25]) tienen también en la superficie una proteína adicional más corta llamada esterasa-hemaglutinina.[26]
La replicación de los coronavirus comienza con la entrada en la célula, momento en que pierde su envoltura, y el genoma de ARN se libera en el citoplasma. El genoma del coronavirus tiene un caperuza metilada en el extremo 5' (extremo cap'), y una cola poliadenilada (poly A) en el extremo 3', dándole un gran parecido al ARN mensajero eucariota. Esto permite que al ARN se le adhieran los ribosomas citoplasmáticos para su traducción. Los coronavirus tienen también una proteína replicasa codificada en su código genético, que le permite generar nuevas copias de su ARN sin necesidad de transcribirse a ADN, usando los recursos de la célula huésped. Esta replicasa es la primera proteína que se sintetiza ya que una vez que el gen que codifica la replicasa es traducido (síntesis proteica), el proceso se detiene por un codón de parada.[27] Esto se conoce como una transcripción anidada. Cuando el transcrito de ARNm solo codifica un gen, se conoce como monocistrónico. El genoma de ARN se replica a cadena negativa y de esta se forman copias positivas de la que se traduce una larga poliproteína, que deberá ser escindida en las distintas proteínas funcionales del virus. Los coronavirus tienen para ello una proteasa denominada Mpro o 3CLpro[28] que corta la poliproteína para dar lugar a las proteínas víricas (maduración de la poliproteína). Esta es una estrategia vírica para la economía genética, ya que le permite codificar un buen número de proteínas con un número pequeño de transcritos a la vez que mejora la tasa de fallos durante la ejecución de la ARN polimerasa.[29][27] Dicha proteasa es un objetivo de fármacos para impedir la replicación del virus.[30]
Los coronavirus humanos fueron descritos por primera vez en la década de 1960 en cavidades nasales de pacientes con un resfriado común. Estos virus fueron nombrados posteriormente coronavirus humano 229E y OC43. Otros dos miembros de esta familia han sido identificados, el HCoV-NL63 en 2004 y HKU1 en 2005. Los cuales circulan globalmente en la población humana y causan aproximadamente un tercio de los casos de resfriado común. Al igual que otros tipos de virus pueden causar enfermedades más graves del sistema respiratorio como bronquitis o neumonía especialmente en personas con factores de riesgo, ancianos, niños y pacientes inmunodeprimidos. Además de afecciones respiratorias también pueden causar enfermedades intestinales y neurológicas.[31]
Existen registros de siete cepas de coronavirus relacionados con enfermedades respiratorias en humanos (HCoV):
Después de la publicación del perfil de los brotes de SARS en 2003, resucitó entre los virólogos un interés por los coronavirus. Durante muchos años, los científicos sabían de solo dos coronavirus humanos (HCoV-229E y OC43-HCoV). El descubrimiento de SARS-CoV añadió un tercer coronavirus humano. A finales de 2004, tres laboratorios de investigación independientes informaron del descubrimiento de un cuarto coronavirus humano, nombrado NL63, NL, y coronavirus de New Haven simultáneamente por varios grupos de investigación. Los tres laboratorios siguen discutiendo sobre cuál de ellos descubrió el virus en primer lugar y por tanto tiene derecho a nombrarlo. A principios de 2005, un equipo de investigación de la Universidad de Hong Kong informó del hallazgo de un quinto coronavirus humano en dos pacientes con neumonía. Lo llamaron coronavirus humano HKU1. El brote de neumonía 2019-20 en Wuhan, China, llevó al hallazgo de un coronavirus nuevo, catalogado como 2019-nCoV por la OMS.[34][35][32][33]
En 2003, tras el brote del SARS (síndrome respiratorio agudo grave), que había comenzado en el año 2002 en Asia, y luego en otras partes del mundo, la Organización Mundial de la Salud (OMS) emitió un comunicado de prensa indicando que un coronavirus de nueva identificación por parte una serie de laboratorios era el agente causante del SARS. El virus fue nombrado oficialmente como coronavirus del SARS (SARS-CoV). Más de 8000 personas resultaron infectadas, alrededor del 10% de los cuales murieron.[26]
En septiembre de 2012, se identificó un nuevo tipo de coronavirus, llamado inicialmente coronavirus nuevo 2012, y ahora con el nombre oficial coronavirus del síndrome respiratorio de Oriente Medio (MERS-CoV). La Organización Mundial de la Salud emitió una alerta mundial poco después. La actualización de la OMS el 28 de septiembre de 2012 declaró que no parecía que el virus se transmitiese fácilmente de persona a persona. Sin embargo, el 12 de mayo de 2013, un caso de transmisión de humano a humano en Francia fue confirmado por el Ministerio de Asuntos Sociales y de Salud de Francia. Además, los casos de transmisión de humano a humano han sido reportados por el Ministerio de Salud de Túnez. Dos casos confirmados parecen haber contraído la enfermedad de su difunto padre, quienes se enfermaron después de una visita a Catar y Arabia Saudita. A pesar de esto, parece que el virus tiene problemas para la difusión de humano a humano, ya que la mayoría de las personas que están infectadas no transmiten el virus.[36][37][38][39][40][41]
Para el 30 de octubre de 2013, había en Arabia Saudita 124 casos y 52 muertes. Después de que el Centro Médico Erasmus neerlandés secuenció el virus, le dio un nombre nuevo, coronavirus humano-Centro Médico Erasmus (HCoV-CEM). El nombre final para el virus es coronavirus del síndrome respiratorio de Oriente Medio (MERS-CoV). En mayo de 2014 se registraron los dos únicos casos de infección con MERS-CoV en los Estados Unidos, ocurrieron en trabajadores de la salud que trabajaron en Arabia Saudita y luego se desplazaron a Estados Unidos. Ambos individuos fueron hospitalizados temporalmente y luego dados de alta. En mayo de 2015, un brote de MERS-CoV se produjo en Corea del Sur, cuando un hombre que había viajado a Oriente Medio, visitó 4 hospitales diferentes en el área de Seúl para tratar su enfermedad. Esto provocó uno de los mayores brotes de MERS-CoV fuera del Medio Oriente. En diciembre de 2019, 2.468 casos de infección MERS-CoV habían sido confirmados por medio de pruebas de laboratorio, casos de los cuales 851 fueron mortales, una tasa de mortalidad de aproximadamente el 34,5%.[42][43][44][45]
El coronavirus de tipo 2 causante del síndrome respiratorio agudo severo,[46] abreviado SARS-CoV-2 (del inglés severe acute respiratory syndrome coronavirus 2)[47] o SRAS-CoV-2,[46] es un tipo de coronavirus causante de la enfermedad por coronavirus de 2019,[48][49][50] cuya expansión mundial provocó la pandemia de COVID-19. Inicialmente fue llamado 2019-nCoV (en inglés, 2019-novel coronavirus, ‘nuevo coronavirus de 2019’) y también, ocasionalmente, HCoV-19 (en inglés, human coronavirus 2019).[51][52] Se descubrió y se aisló por primera vez en Wuhan, China. Tiene un origen zoonótico, es decir, que se transmitió de un huésped animal a uno humano.[53]
Es un clado dentro de la familia de los Coronaviridae, género Betacoronavirus, subgénero Sarbecovirus, especie virus SARS[54](virus relacionado con el síndrome respiratorio agudo severo o grave).[55]
El genoma del virus está formado por una sola cadena de ARN, y se clasifica como un virus ARN monocatenario positivo. Su secuencia genética se ha aislado a partir de una muestra obtenida de un paciente afectado por neumonía en la ciudad china de Wuhan, aunque la falta de experimento de control doble ciego en la técnica de secuenciación publicada puede poner en cuestionamiento la validez científica de la técnica [56].[57][58][59][60][61] Se detectó por primera vez el 12 de noviembre de 2019. Puede producir el contagio de una persona a otra mediante las gotas de saliva expulsadas a través de la tos y el estornudo o al espirar (véase gotitas de Flügge).[62][63] Puede provocar enfermedad respiratoria aguda y neumonía grave en los seres humanos.[64]
Aunque previamente no había ningún tratamiento específico aprobado oficialmente, ya se habían desarrollado algunos antivirales existentes, así como el tratamiento con plasma convaleciente y la dexametasona, que parecen tener una mayor eficacia en el manejo de los síntomas o que parecen acortar el periodo de recuperación en poblaciones especiales.[65][66] En diciembre de 2020 comenzó una campaña de vacunación con las primeras vacunas aprobadas, que se prolongó durante 2021 y se mantendrá durante 2022[cita requerida] Fue Pfizer - BioNTech, con la vacuna Comirnaty, los laboratorios pioneros en patentar una vacuna[67] y posteriormente, los laboratorios Moderna y AstraZeneca se unieron a esta carrera por la vacuna.[68]Los coronavirus han sido reconocidos como causantes de condiciones patológicas en veterinaria desde principios de 1970. A excepción de la bronquitis infecciosa aviar, las principales enfermedades relacionadas tienen principalmente una ubicación intestinal.
Los coronavirus infectan principalmente el tracto respiratorio y gastrointestinal superior de mamíferos y aves. Actualmente se conocen siete cepas del coronavirus que infectan a los humanos. Se cree que los coronavirus causan un porcentaje significativo de todos los resfriados comunes en personas adultas y niños. Los coronavirus causan resfriados con síntomas importantes; por ejemplo, fiebre, inflamación de las adenoides de la garganta, en los seres humanos principalmente en las temporadas de invierno y primavera temprana. Los coronavirus puede causar neumonía, ya sea neumonía viral directa o una neumonía bacteriana secundaria, y la bronquitis, ya sea bronquitis viral directa o una bronquitis bacteriana secundaria. El coronavirus humano más conocido fue descubierto en 2003, SARS-CoV que causa el síndrome respiratorio agudo grave (SARS), tiene una patogénesis única porque causa que infecciones de las vías respiratorias tanto superior como inferior. La importancia económica y el impacto de los coronavirus como agentes causantes del resfriado común son difíciles de evaluar debido a que, a diferencia de los rinovirus (otro virus del resfriado común), los coronavirus humanos son difíciles de cultivar en el laboratorio.[69][70]
Los coronavirus también causan una serie de enfermedades en los animales de granja y mascotas domesticadas, algunos de los cuales pueden ser graves y son una amenaza para la industria agrícola. En los pollos, el virus de la bronquitis infecciosa (IBV), es un coronavirus que afecta no solo las vías respiratorias, sino también el tracto urogenital. El virus puede propagarse a los diferentes órganos del cuerpo de la gallina. Los que tienen consecuencias económicamente significativas en los animales de granja incluyen el coronavirus porcino (coronavirus de la gastroenteritis transmisible, TGE) y el coronavirus bovino, el cual causa diarrea en los animales jóvenes. Coronavirus felino: existen dos formas, el coronavirus entérico felino es un patógeno de importancia clínica menor, pero la mutación espontánea de este virus puede provocar una peritonitis infecciosa felina (FIP), una enfermedad asociada con una alta mortalidad. Del mismo modo, hay dos tipos de coronavirus que infectan a los hurones: el coronavirus entérico de hurón causa un síndrome gastrointestinal conocido como epizoótica catarral enteritis (ECE), y una versión sistémica más letal del virus (como FIP en los gatos), conocido en hurones como coronavirus sistémico de hurón (FSC). Hay dos tipos de coronavirus canino (CoVC), uno que causa la enfermedad gastrointestinal leve y uno que causa enfermedad respiratoria. El virus de la hepatitis del ratón (MHV) es un coronavirus que causa una enfermedad epidémica murina con una mortalidad alta, especialmente entre las colonias de ratones de laboratorio.[71][72][73] El virus de la sialodacrioadenitis (sialo saliva, dacrio lágrima) es un coronavirus altamente infeccioso de ratas de laboratorio, que puede transmitirse entre individuos por contacto directo o indirectamente por las secreciones en aerosol. Las infecciones agudas tienen una alta morbilidad y tropismo para las glándulas salivales, lacrimales y harderiana.[74]
Uno relacionado con el coronavirus murciélago Rinolophus HKU2 llamado coronavirus del síndrome de diarrea aguda porcina (SADS-CoV) (del inglés swine acute diarrhea syndrome) causa diarrea en cerdos.[75]
Antes del descubrimiento de SARS-CoV, MHV había sido estudiado tanto in vivo como in vitro, así como a nivel molecular. Algunas cepas de MHV causaron una encefalitis desmielinizante progresiva en ratones a los que se ha utilizado como modelo murino para la esclerosis múltiple. Importantes esfuerzos de investigación se han centrado en dilucidar la patogénesis viral de estos coronavirus de animales, especialmente por los virólogos interesados en las enfermedades zoonóticas y veterinarios.[76]
Otra enfermedad veterinaria nueva, virus de la diarrea epidémica porcina (PED o PEDV), ha surgido en todo el mundo. Su importancia económica es aún poco clara, pero muestra una alta mortalidad en los lechones.[78][79][80]
Los géneros, subgéneros y especies incluidas en Orthocoronavirinae son:[81]
Orthocoronavirinae, comúnmente conocidos como coronavirus, es una subfamilia de virus ARN monocatenario positivos perteneciente a la familia Coronaviridae. Se subdivide en los géneros Alphacoronavirus, Betacoronavirus, Gammacoronavirus y Deltacoronavirus. Estos incluyen genogrupos filogenéticamente similares de virus con una nucleocápside de simetría helicoidal con envoltura cuyos viriones pueden medir entre aproximadamente 50 y 200 nm de diámetro. Su material genético es el de mayor tamaño dentro de los virus de ARN, con genomas que van desde los 26 a 32 kilonucleótidos. Se les llama coronavirus por la corona de puntas que se ve alrededor de la superficie del virus. Fue descrito por primera vez en 1965.
Los coronavirus pueden infectar aves y mamíferos produciendo una serie de enfermedades respiratorias y digestivas, muchas de ellas letales trayendo como consecuencia serios perjuicios en la avicultura y la ganadería; también pueden infectar al ser humano causando enfermedades que van desde el resfriado común hasta enfermedades más graves, como bronquitis, bronquiolitis, neumonía, el síndrome respiratorio de Oriente Medio (MERS), el síndrome respiratorio agudo grave (SARS) y el COVID-19, entre otras. La mayoría de las personas se infectan con estos virus en algún momento de su vida.
Hasta la fecha se han registrado cuarenta y cinco especies de coronavirus. Varias especies son de reciente investigación debido a que varias cepas particulares no habían sido identificadas previamente en humanos. Existe poca información sobre la transmisión, gravedad e impacto clínico y no existen tratamientos aprobados hasta la fecha, sin embargo se pueden tratar varios de los síntomas, las opciones terapéuticas dependen del estado clínico de cada paciente.
El género Alphacoronavirus —anteriormente conocido como Coronavirus grupo 1 (CoV-1)— incluye los subgrupos 1a y 1b, cuyos integrantes más representativos son el coronavirus humano 229E (HCoV-229E) y HCoV-NL63, así como la nueva especie alfacoronavirus 1 —incluyendo virus de la gastroenteritis transmisible porcina (TGEV)—, respectivamente. El género Betacoronavirus —anteriormente Betacoronavirus grupo 2 (Cov-2)— incluye varios subgrupos. Los más prominentes (subgrupos 2a y 2b) tienen como especies tipo las especies de coronavirus murino —incluido el virus de la hepatitis de ratón (MHV)– y el SARS-CoV, respectivamente. Los géneros Alphacoronavirus y Betacoronavirus provienen del pool genético que tiene a murciélagos como huésped. El género Gammacoronavirus incluye todos los coronavirus aviares identificados hasta 2009.
Orthocoronavirinae
Les coronavirus (CoV) sont des virus qui constituent la sous-famille Orthocoronavirinae de la famille Coronaviridae. Le nom « coronavirus », du latin signifiant « virus à couronne », est dû à l'apparence des virions sous un microscope électronique, avec une frange de grandes projections bulbeuses qui évoquent une couronne solaire[2].
Les coronavirus sont munis d'une enveloppe virale incluant une capside caractérisée par des protéines en forme de massue (appelées spicules). Ils ont un génome à ARN monocaténaire (c'est-à-dire à un seul brin), de sens positif (groupe IV de la classification Baltimore), de 26 à 32 kilobases (ce qui en fait les plus grands génomes parmi les virus à ARN)[3]. Ils se classent parmi les Nidovirales, ordre de virus produisant un jeu imbriqué d'ARNm sous-génomiques lors de l'infection. Des spicules, une enveloppe, membrane et capside contribuent à la structure d'ensemble de tous les coronavirus. Ils peuvent muter et se recombiner[4].
Les chauves-souris et les oiseaux, en tant que vertébrés volants à sang chaud, seraient les hôtes idéaux pour les coronavirus assurant l'évolution et la dissémination du coronavirus[5]. Les coronavirus sont normalement spécifiques à un taxon animal comme hôte, mammifères ou oiseaux selon leur espèce ; mais ils peuvent parfois changer d'hôte à la suite d'une mutation. Leur transmission interhumaine se produit principalement par contacts étroits via des aérosols respiratoires générées par les éternuements, la toux ou la phonation. Plus de 500 types de coronavirus ont été isolées chez la chauve-souris et il existerait plus de 5 000 types de coronavirus[6].
Sept principaux coronavirus sont généralement cités comme pouvant contaminer l'humain[7]. Un huitième a été identifié : le B814[8] (le premier coronavirus humain identifié), mais cette souche semble ne plus circuler.
Quatre coronavirus en circulation sont considérés comme sources d'infection bénignes : 229E, NL63, OC43 et HKU1. Ils seraient la cause de 15 à 30 % des rhumes courants.
Plus récemment ont été identifiés trois types de coronavirus responsables de graves pneumopathies :
Les coronavirus existent probablement depuis au moins des centaines de millions d'années, mais du point de vue de l'épidémiologie et de l'histoire médicale et en tant que zoonose c'est au XXIe siècle qu'ils ont pris de l'importance : « cinq des sept coronavirus humains ont été isolés au cours de ce siècle. Et malheureusement, les trois derniers sont entrés dans notre vie avec les craintes liées à une épidémie, une pandémie ou à la mort »[9].
C'est en 1930 aux États-Unis que la première maladie due à un coronavirus est observée, chez des volailles. L'année suivante, un médecin décrit dans un article la maladie qui cause une détresse respiratoire chez la poule et une diminution de la ponte et de la qualité des œufs. En 1937, l'agent infectieux, le virus de la bronchite infectieuse aviaire (IBV pour Infectious Bronchitis Virus) est isolé.
En 1946, un autre coronavirus est identifié, le Coronavirus de la gastro-entérite transmissible porcine (TGEV). Indépendamment, en 1949 à New York et 1951 à Londres, deux équipes découvrent le virus de l'hépatite murine chez une souris paralysée[10].
En 1965, le premier coronavirus infectant l'être humain (la souche B814) est découvert. Et rapidement, d'autres suivent : 229E en 1966 et OC43 en 1967[11], qui sont la cause de rhumes plus ou moins graves selon les personnes. L'année suivante, ils sont observés au microscope électronique par June Almeida et David Tyrrell qui mettent en évidence leur structure en couronne[12]. La relation est faite entre tous ces virus, et le terme de « coronavirus » est pour la première fois utilisé dans la revue Nature en 1968[2],[10].
Le dernier coronavirus humain (ou récemment humanisé, très probablement à partir d'une ou plusieurs souches portées par des chauves-souris) semble avoir émergé à Wuhan en Chine en 2019 : le SARS-CoV-2. La maladie qu'il cause (Covid-19) a provoqué en quelques mois la première grande pandémie à coronavirus, caractérisée par un R0 élevé (2,3 en moyenne d'après les estimations disponibles en avril 2020, mais qui semble pouvoir atteindre 5,7) ; avec un taux de létalité de 6,3 (très variable selon les âges et les contextes, pouvant parfois dépasser 15%)[9].
Pandémie de Coronavirus Pandémie Date Cas confirmés Décès Guérisons Sous-type impliqué Épidémie de SRAS de 2002-2004 2002-2004 8 096 774 - Sars-Cov (SRAS) Coronavirus du syndrome respiratoire du Moyen-Orient 2012-2014 361 107 - MERS-CoV Pandémie de Covid-19 (En cours) 2019-2021 + 250 847 494 (10 novembre 2021)[13] + 5 064 350 (10 novembre 2021)[13] + 220 905 435 (10 novembre 2021)[13] SARS-CoV-2 (Covid-19)La taxonomie de ces nouveaux virus fait d'abord débat, pour finalement aboutir en 1975 à la création d'une nouvelle famille (Coronaviridae) et d'une nouvelle sous-famille (Orthocoronavirinae) par l'International Committee on Taxonomy of Viruses[10].
Le terme coronavirus (du latin corona et virus, littéralement « virus à couronne »[15]) provient de l'apparence des virions au microscope électronique, caractérisée par une frange de grandes protubérances entourant l'enveloppe avec l'apparence d'une couronne, par analogie avec la couronne solaire[2].
Les hôtes idéaux des coronavirus, en tant que vertébrés volants à sang chaud, sont les chauves-souris (pour les Alphacoronavirus et les Betacoronavirus) et les oiseaux (pour les Gammacoronavirus et les Deltacoronavirus). Ces espèces-réservoir assurent l'évolution et la dissémination des coronavirus[5]. Chez d'autres espèces, les symptômes varient (maladies des voies respiratoires supérieures chez la poule, diarrhée chez la vache ou le porc, des voies digestives chez le chat et le chien, etc.). Parfois, aucun symptôme n'est associé à leur présence (ex. : coronavirus du béluga).
L'être humain abrite naturellement quatre types de coronavirus bénins, qui provoquent des infections des voies respiratoires, comme le rhume, et plus rarement affectent les systèmes gastro-intestinaux, cardiaques et nerveux[16].
Les groupes de coronavirus ont normalement un hôte animal spécifique (mammifères ou oiseaux[17]) mais ils peuvent parfois changer d'hôte à la suite d'une mutation. Ce sont de telles mutations qui ont probablement conduit à l'apparition de souches causant de graves infections chez l'homme (SRAS, MERS et Covid-19).
On a longtemps pensé que les coronavirus avaient un tropisme uniquement respiratoire ou gastrointestinal (traduit par des pneumonies et entérocolites dans les cas graves), mais un nombre croissant d'études montrent un tropisme bien plus large, cardiovasculaire notamment, et neurologique également (dès les années 1980, on a montré que plusieurs coronavirus, dont en dernier cas le SARS-CoV-2 sont clairement aussi neuroinvasifs et neurotropes[18],[19],[20], au point que cette diversité de tropismes et de symptômes font des coronavirus (murins notamment, regroupées sous le sigle de MHV) un modèle animal pour l'étude de maladies humaines aussi variées que la sclérose en plaques, l’hépatite virale ou la pneumonie (S. R. Weiss et al. 2011). Le MHV pénètre le Système nerveux central (SNC) via les neurones du nerf olfactif, et peut causer une encéphalite aiguë ou une maladie démyélinisante chronique s'il y persiste (il peut aussi se propager jusqu’à la moelle épinière)[19],[21].
En 2002, l’apparition du Sars-CoV, un virus responsable d'une maladie infectieuse des poumons, pousse l’Union européenne à lancer plusieurs programmes afin de ne pas être prise au dépourvu en cas de nouvelles émergences. Dès 2004, l’équipe de Bruno Canard, directeur de recherche CNRS à Aix-Marseille, spécialiste des coronavirus, grâce aux réseaux collaboratifs européens, affiche des résultats prometteurs. « Nous avions eu cette idée qui s’est révélée fructueuse : les virus ont une capacité énorme à être différents, variés, avec de larges familles. Nous les avons donc étudiés tous en même temps, afin d’en avoir un modèle type qui nous permettrait, en cas de menace d’un virus inconnu, d’en trouver un proche, d’où nous pourrions extraire des données scientifiques[22]. »
Mais dès 2006, l’intérêt des politiques pour le Sars-CoV disparaît. La crise financière de 2008 accélère le désengagement de l’Europe et de la France pour la recherche, les stratégies de recherche fondamentale perdent leurs financements. Aussi, en 2015, Bruno Canard dénonce le désengagement européen et français dans le secteur des sciences et adresse avec ses collègues belges et hollandais, des lettres d’intention à la Commission européenne expliquant qu’il existe neuf familles de virus pour lesquelles une émergence est possible. « Le premier sur la liste était le flavivirus, explique-t-il. Le second, le coronavirus. Un an plus tard, apparaissait Zika, un flavivirus ». Or, la Commission européenne ne donnera jamais de réponse. Et en 2020 surgit le Sars-CoV-2, un coronavirus[22] engendrant la Covid-19.
Ce virus enveloppé est constitué d'une enveloppe virale entourant une capside hélicoïdale qui contient le brin d'ARN. La taille du génome de ces virus varie d'environ 26 à 32 kilobases, valeurs parmi les plus élevées chez les virus à ARN.
Les coronavirus ont en commun des protéines désignées par une lettre indiquant leur localisation : S (protubérances), E (enveloppe), M (membrane) et N (nucléocapside). Certains, notamment ceux du sous-groupe A du genre Betacoronavirus, ont une protéine HE (hémagglutinine estérase (en)) caractéristique. Le coronavirus du SRAS présente en outre sur la protéine S un site de liaison spécifique à l'enzyme de conversion de l'angiotensine 2[23] qui lui sert de point d'entrée dans la cellule hôte.
La taille physique du virion est classiquement donnée comme étant de 120 à 160 nm[24] ou comme étant de l'ordre de 125 nm[25]. Toutefois le SARS-CoV-2, responsable de la Covid-19 a été annoncé plus récemment comme mesurant approximativement de 60 à 140 nm, et comme étant de forme elliptique avec de nombreuses variations[26].
Tous les CoV ont un génome d'ARN non-segmentés (simple brin) organisé de la même manière : les deux tiers environ du génome contiennent deux grands « cadres de lecture ouverts » et se chevauchant (dits ORF1a et ORF1b). Ces deux cadres sont traduits en « polyprotéines réplicase » pp1a et pp1ab. « Ces polyprotéines sont ensuite traitées pour générer 16 protéines non structurales, désignées nsp1 ~ 16. La partie restante du génome contient des ORF pour les protéines structurales, y compris la pointe (S), l'enveloppe (E), la membrane (M) et la nucléoprotéine (N). Un certain nombre de protéines accessoires spécifiques à la lignée sont également codées par différentes lignées de CoV »[3],[27],[28],[29].
Elle se fait en six étapes successives (voir illustration) :
Sept types de coronavirus infectent couramment l'homme[31], dont trois causent des infections graves.
Les quatre premiers types connus sont sans gravité : les coronavirus humains 229E, NL63, OC43 et HKU1, inconnus chez la chauve-souris. Ils causent des rhumes avec fièvre et des maux de gorge dus à des végétations adénoïdes gonflées, principalement en hiver et au début du printemps[32].
Les coronavirus seraient la cause de 15 à 30 % des rhumes courants[33].
Trois types de coronavirus qui ne se trouvent pas naturellement chez l'homme mais chez des mammifères ont été découverts plus récemment et ont été à l'origine d'infections graves des poumons (pneumopathie virale) :
Selon le virus en cause, les formes graves de la maladie ont leurs particularités. Par exemple, la diarrhée était très fréquente dans le SRAS mais rare dans la maladie à coronavirus 2019.
Trois principales sources sont utilisées : l'Institut Pasteur, l'OMS et les CDC américains[35].
Au vu des séquences génomiques disponibles, deux grands taxons animaux seraient le réservoir principal des CoVs :
Au vu des connaissances disponibles, les coronavirus semblaient avoir besoin d'hôtes intermédiaires (toujours des mammifères) pour s'« humaniser », c'est-à-dire muter pour pouvoir infecter l'Homme.
Des hôtes intermédiaires connus ont été :
Pour la pandémie de 2019-2020, se reporter aux articles dont les noms suivent.
La transmission interhumaine des coronavirus se fait principalement par les gouttelettes ou des aérosols respiratoires expectorées par une personne infectée (via la toux, les éternuements, des postillons, ou parfois par le simple fait de parler fort ou en criant) quand les particules virales sont inhalées par une personne se trouve à proximité. La transmission et la contagiosité varient aussi selon le coronavirus, et peut-être selon sa souche au sein d'une épidémie.
La prophylaxie passe par une prévention primaire visant à limiter la transmission du virus : éviter les contacts (surfaces potentiellement contaminées, poignées de main, embrassades), se laver les mains fréquemment, éviter de se toucher les yeux, le nez ou la bouche, par où le virus peut s'introduire dans l'organisme. En cas de symptômes de type toux ou rhume, se maintenir à au moins 1 mètre de toute personne et éviter d'émettre des particules contaminées[54].
D'autres recommandations comprennent[55] :
Dans le cas du SRAS, des médicaments ont été utilisés pour tenter d'enrayer l'épidémie : la ribavirine, un analogue de nucléotides, des anti-inflammatoires stéroïdiens et, après identification formelle de l'agent pathogène et des criblages de sensibilité, l'interféron-alpha et des inhibiteurs de protéases. Leur efficacité est encore sujette à caution. Aucun n'a fait l'objet d'une étude clinique adéquate : beaucoup d'études disponibles ne permettent pas de conclusions scientifiques claires car elles ont été réalisées sur de petits nombres de sujets ou alors sans protocole ou dose fixe. Certaines indiquent même que ces traitements pourraient avoir nui à l'éradication du virus[56].
Bruno Canard dénonce en mars 2020 l'emballement et publie une lettre ouverte Coronavirus : la science ne marche pas dans l’urgence ![57]. Il déclare : « Un vaccin demande au mieux 18 mois de recherches. Et pour des virus non prévisibles, qui changent, il n’est pas adapté. Mieux vaut faire des médicaments qui ont un large spectre dans une famille virale. Cela peut nécessiter 5 ans, parfois 10. D’où l’importance de l’anticipation scientifique[22]. »
L'éradication rapide de l'épidémie de SRAS précédente n'a pas laissé place à beaucoup d'essais cliniques. Des vaccins à base de virus inactivé, et d'autres fondés sur les protéines S et N, sont à l'étude depuis plusieurs années[58]. Pour les vaccins, les éléments viraux produisant l'immunité ne sont souvent pas assez conservés dans la même famille virale. « Ainsi, s'il y avait eu un vaccin contre le coronavirus de 2003, il est pratiquement certain qu'il n'aurait pas marché de manière satisfaisante contre [la] Covid-19 » (Bruno Canard)[59].
Les coronavirus sont nommés par un groupe d'étude[60] travaillant au sein de l'ICTV (International committee on Taxonomy of viruses)[61].
Les coronavirus (CoV) sont des virus à ARN monocaténaire de sens positif (groupe IV de la classification Baltimore) correspondant à la sous-famille Orthocoronavirinae de la taxonomie de l'ICTV[1], dans la famille Coronaviridae, et de l'ordre Nidovirales[62],[63].
Selon les caractéristiques de leurs séquences protéiques, les CoV sont classés en 4 genres (alpha-CoV, beta-CoV, gamma-CoV et delta-CoV), qui tous contiennent des virus pathogènes pour les mammifères[4] :
Remarques :
La sous-famille Orthocoronavirinae de la famille Coronaviridae est organisée en 4 genres, 22 sous-genres et une quarantaine d'espèces[67] :
Orthocoronavirinae
Les coronavirus (CoV) sont des virus qui constituent la sous-famille Orthocoronavirinae de la famille Coronaviridae. Le nom « coronavirus », du latin signifiant « virus à couronne », est dû à l'apparence des virions sous un microscope électronique, avec une frange de grandes projections bulbeuses qui évoquent une couronne solaire.
Les coronavirus sont munis d'une enveloppe virale incluant une capside caractérisée par des protéines en forme de massue (appelées spicules). Ils ont un génome à ARN monocaténaire (c'est-à-dire à un seul brin), de sens positif (groupe IV de la classification Baltimore), de 26 à 32 kilobases (ce qui en fait les plus grands génomes parmi les virus à ARN). Ils se classent parmi les Nidovirales, ordre de virus produisant un jeu imbriqué d'ARNm sous-génomiques lors de l'infection. Des spicules, une enveloppe, membrane et capside contribuent à la structure d'ensemble de tous les coronavirus. Ils peuvent muter et se recombiner.
Les chauves-souris et les oiseaux, en tant que vertébrés volants à sang chaud, seraient les hôtes idéaux pour les coronavirus assurant l'évolution et la dissémination du coronavirus. Les coronavirus sont normalement spécifiques à un taxon animal comme hôte, mammifères ou oiseaux selon leur espèce ; mais ils peuvent parfois changer d'hôte à la suite d'une mutation. Leur transmission interhumaine se produit principalement par contacts étroits via des aérosols respiratoires générées par les éternuements, la toux ou la phonation. Plus de 500 types de coronavirus ont été isolées chez la chauve-souris et il existerait plus de 5 000 types de coronavirus.
Sept principaux coronavirus sont généralement cités comme pouvant contaminer l'humain. Un huitième a été identifié : le B814 (le premier coronavirus humain identifié), mais cette souche semble ne plus circuler.
Quatre coronavirus en circulation sont considérés comme sources d'infection bénignes : 229E, NL63, OC43 et HKU1. Ils seraient la cause de 15 à 30 % des rhumes courants.
Plus récemment ont été identifiés trois types de coronavirus responsables de graves pneumopathies :
Le SARS-CoV, agent pathogène du syndrome respiratoire aigu sévère (SRAS) en 2002-2004 ; Le MERS-CoV, celui du syndrome respiratoire du Moyen-Orient à partir de 2012 ; Le SARS-CoV-2, celui de la maladie à coronavirus 2019 (Covid-19) apparue en Chine en 2019 et responsable d'une sévère pandémie depuis 2019.Orthocoronavirinae è una sottofamiglia di virus, noti anche come coronavirus, della famiglia Coronaviridae, del sottordine Cornidovirineae, dell'ordine Nidovirales.[1] In passato era classificata come genere.
Suddivisa nei generi (in passato sottogeneri) Alphacoronavirus, Betacoronavirus, Gammacoronavirus e Deltacoronavirus, questi includono genogruppi filogeneticamente compatti di RNA avvolto, a senso positivo, e con un nucleocapside di simmetria elicoidale. Alphacoronavirus e Betacoronavirus derivano dal pool genico dei pipistrelli.
La "dimensione genomica" dei coronavirus varia da circa 26 a 32 kilobasi, straordinariamente grande per un virus a RNA.[2][3] Il loro numero sta crescendo rapidamente con diversi nuovi coronavirus scoperti di recente, tra cui SARS-CoV-1 scoperto nel 2002, MERS-CoV nel 2012 e SARS-CoV-2 scoperto nel 2019 a Wuhan, in Cina.
Il nome "coronavirus" deriva dal termine latino corona, a sua volta derivato dal greco κορώνη (korṓnē, "ghirlanda"), che significa "corona" o "aureola". Ciò si riferisce alle spinule[4][5] (proteine S) formate dai virioni (la forma infettiva del virus) visibile al microscopio elettronico, che presenta una serie di glicoproteine superficiali che danno un'immagine che ricorda una corona reale o una corona solare. Questa morfologia a spinula è dovuta ai peplomeri virali, che sono proteine che popolano la superficie del virus e determinano il tropismo nell'ospite.
Si pensa che il primo caso riportato di coronavirus sia dovuto a veterinari tedeschi che nel 1912 descrissero il caso di un gatto febbricitante con un enorme ingrossamento del ventre. Ma solo negli anni 1960 un virus con struttura a forma di corona che causava comuni raffreddori venne isolato e venne associato al fenomeno, inclusi altri riscontrati in svariati animali. I ricercatori pensarono che i coronavirus fossero capaci di causare negli umani solo sintomi lievi, fino a che non ci fu l'epidemia di SARS nel 2003[6].
I coronavirus sono responsabili di diverse patologie nei mammiferi e negli uccelli, dal verificarsi di diarrea nei bovini e nei suini e a malattie respiratorie delle vie superiori nei polli. Nell'uomo, provocano infezioni delle vie respiratorie, spesso di lieve entità come il raffreddore comune, ma in rari casi potenzialmente letali come polmoniti e bronchiti.
I coronavirus sono stati responsabili delle gravi epidemie di SARS del novembre 2002, di quella della MERS del 2012 e della pandemia di COVID-19 del 2020.
I coronavirus sono virus a RNA positivo dal diametro di circa 80-160 nm, il che li rende tra i più grandi virus capaci di attaccare l'essere umano. Con 30 000 basi genetiche, i coronavirus hanno il più ampio genoma tra i virus a RNA, inoltre è uno dei pochi virus a RNA ad avere un meccanismo di correzione di lettura genetica che previene l'accumulo di mutazioni. Il nome del virus deriva dalla classica forma apprezzabile al microscopio elettronico a trasmissione a "corona". Questo aspetto è dato dalla presenza di spinule rappresentate dalla glicoproteina che attraversa il pericapside, raggiungendo il rivestimento proteico, detta proteina spinula o proteina S, con proprietà emoagglutinanti e di fusione. La struttura del virus è quella più o meno tipica dei virus rivestiti: presenta quindi un nucleocapside a simmetria elicoidale e un pericapside costituito da un doppio strato fosfolipidico di origine cellulare; tra questi due strati si interpone un coat proteico costituito dalla proteina M (matrice). Nel nucleocapside si ritrova il genoma costituito da un ssRNA+ (un filamento di RNA singolo a polarità positiva) da 27-30 kilo basi che codifica per 7 proteine virali ed è associato alla proteina N.
I coronavirus si attaccano alla membrana cellulare delle cellule bersaglio grazie alle loro proteine S che interagiscono con l'aminopeptidasi N della membrana. Alcuni coronavirus possono legare l'acido N-acetil neuraminico grazie all'espressione della glicoproteina E3. Non è chiaro se la penetrazione della cellula sia effettuata mediante fusione del pericapside con la membrana plasmatica o per endocitosi. All'interno del citoplasma della cellula il coronavirus rilascia il suo RNA a singolo filamento positivo che si attacca ai ribosomi, dove viene tradotto. La traduzione comporta la produzione di una RNA-polimerasi RNA-dipendente (proteina L) che trascrive un RNA a filamento negativo da cui poi è possibile ottenere nuovi RNA a filamento positivo del coronavirus, nonché le sette proteine che esso codifica. A ciascun nuovo filamento di RNA positivo si associa la proteina N, mentre le proteine del pericapside si integrano nella membrana del reticolo endoplasmatico. Un traslocatore trasferisce i nuovi nucleocapsidi nel lume del reticolo endoplasmatico; successivamente da questo gemmano vescicole che costituiscono i nuovi virioni che possono essere rilasciati per esocitosi.
La famiglia dei coronavirus è stata divisa in quattro generi distinti:[7][8]
Il genere alphacoronavirus (precedentemente noto come gruppo 1 dei Coronavirus, CoV-1) comprende i sottogruppi 1a e 1b, che sono prototipati dal coronavirus umano 229E (HCoV-229E) e HCoV-NL63, nonché dalla nuova specie alphacoronavirus 1 (incluso virus della gastroenterite trasmissibile suina, TGEV), rispettivamente.
Il genere betacoronavirus (precedentemente gruppo 2 dei coronavirus, Cov-2) comprende diversi sottogruppi, con i più importanti (sottogruppi 2a e 2b) prototipati dalla specie murine coronavirus (incluso il virus dell'epatite murina, MHV) e SARS-related coronavirus. Si divide nei sottogeneri Embecovirus, Hibecovirus, Merbecovirus, Nobecovirus e Sarbecovirus.
Il genere gammacoronavirus comprende tutti i coronavirus aviari identificati fino al 2009.
I coronavirus sono stati scoperti negli anni sessanta dalle cavità nasali dei pazienti con raffreddore comune.[9] Questi virus furono successivamente chiamati Coronavirus umano 229E (HCoV-229E) e Coronavirus umano OC43 (HCoV-OC43).[10] Sono stati identificati altri due membri di questa famiglia (Coronavirus umano NL63, HCoV-NL63, nel 2004; Coronavirus umano HKU1, HCoV-HKU1, nel 2005) e sono stati coinvolti in infezioni del tratto respiratorio più gravi.
Non esistono vaccini o farmaci antivirali considerati validi dalla comunità scientifica per la prevenzione o per il trattamento delle patologie indotte.
Si ritiene che i coronavirus causino una percentuale significativa di tutti i raffreddori comuni negli adulti e nei bambini. I sintomi che si riscontrano più frequentemente sono febbre e adenoidite acuta con maggior incidenza durante l'inverno e l'inizio della primavera.[11] In molti casi i coronavirus possono causare polmonite, polmonite virale diretta o polmonite batterica secondaria; inoltre possono portare anche allo sviluppo di bronchite, bronchite virale diretta o bronchite batterica secondaria.[12]
I ceppi causa delle principali patologie che interessano l'uomo appartengono al genere Betacoronavirus.[13]
Il coronavirus umano scoperto nel 2003, SARS-CoV-1, causa una grave sindrome respiratoria acuta (SARS) e ha una patogenesi unica, perché causa infezioni del tratto respiratorio superiore e inferiore.[12]
La variante SARS dei coronavirus, apparsa inizialmente in Cina nella provincia del Guangdong nel novembre 2002 e isolata per la prima volta l'anno successivo, ha le stesse identiche caratteristiche morfologiche degli altri coronavirus, ma sembra sia una specie del tutto nuova derivata probabilmente da un serbatoio animale (non ancora noto) che ben si è adattato all'uomo. Tra i fattori che il virus della SARS utilizza per incrementare notevolmente la sua virulenza rispetto agli altri coronavirus, c'è un potente sistema di inibizione dell'interferone.
Un altro focolaio pericoloso provocato da un diverso ceppo di coronavirus ha avuto inizio nel giugno 2012 in Arabia Saudita. La malattia è stata perciò indicata col nome di sindrome respiratoria mediorientale da Coronavirus o MERS (dall'acronimo in inglese). Sono stati accertati con test di laboratorio almeno 2000 casi nel mondo, di cui oltre i 3/4 in Arabia Saudita;[14] fino al giugno 2015 c'erano già stati oltre 500 morti (su circa 1500 casi registrati fino a quella data).[15]
Il 31 dicembre 2019 è stato segnalato un nuovo ceppo di questo virus a Wuhan, in Cina,[16] identificato come un nuovo ceppo di β-CoV dal Gruppo 2B con una somiglianza genetica del 70% circa rispetto al SARS-CoV-1. Il nuovo ceppo, di conseguenza, è stato nominato SARS-CoV-2.
A gennaio 2020 sono conosciuti 7 ceppi di coronavirus in grado di infettare gli umani:
La trasmissione dei coronavirus tra umani avviene principalmente attraverso le goccioline respiratorie emesse da un individuo infetto mediante tosse o starnuti, che successivamente vengono inalate da un soggetto sano che si trovi nelle vicinanze. Sembrerebbe che sia possibile infettarsi anche dopo aver toccato superfici o oggetti ove sia presente il virus e portando successivamente le mani verso la propria bocca o verso il naso o gli occhi.[20]
Sebbene i virus respiratori siano trasmissibili solitamente quando il soggetto malato presenta anche i sintomi, il coronavirus SARS-CoV-2 può diffondersi anche in occasione di un contatto ravvicinato con un paziente infetto asintomatico.[20]
Con la sigla nCoV vengono genericamente indicate nuove specie o ceppi di Coronavirus che non sono mai stati precedentemente identificati nell'uomo.[21]
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url (aiuto). Orthocoronavirinae è una sottofamiglia di virus, noti anche come coronavirus, della famiglia Coronaviridae, del sottordine Cornidovirineae, dell'ordine Nidovirales. In passato era classificata come genere.
Suddivisa nei generi (in passato sottogeneri) Alphacoronavirus, Betacoronavirus, Gammacoronavirus e Deltacoronavirus, questi includono genogruppi filogeneticamente compatti di RNA avvolto, a senso positivo, e con un nucleocapside di simmetria elicoidale. Alphacoronavirus e Betacoronavirus derivano dal pool genico dei pipistrelli.
La "dimensione genomica" dei coronavirus varia da circa 26 a 32 kilobasi, straordinariamente grande per un virus a RNA. Il loro numero sta crescendo rapidamente con diversi nuovi coronavirus scoperti di recente, tra cui SARS-CoV-1 scoperto nel 2002, MERS-CoV nel 2012 e SARS-CoV-2 scoperto nel 2019 a Wuhan, in Cina.
Il nome "coronavirus" deriva dal termine latino corona, a sua volta derivato dal greco κορώνη (korṓnē, "ghirlanda"), che significa "corona" o "aureola". Ciò si riferisce alle spinule (proteine S) formate dai virioni (la forma infettiva del virus) visibile al microscopio elettronico, che presenta una serie di glicoproteine superficiali che danno un'immagine che ricorda una corona reale o una corona solare. Questa morfologia a spinula è dovuta ai peplomeri virali, che sono proteine che popolano la superficie del virus e determinano il tropismo nell'ospite.
Si pensa che il primo caso riportato di coronavirus sia dovuto a veterinari tedeschi che nel 1912 descrissero il caso di un gatto febbricitante con un enorme ingrossamento del ventre. Ma solo negli anni 1960 un virus con struttura a forma di corona che causava comuni raffreddori venne isolato e venne associato al fenomeno, inclusi altri riscontrati in svariati animali. I ricercatori pensarono che i coronavirus fossero capaci di causare negli umani solo sintomi lievi, fino a che non ci fu l'epidemia di SARS nel 2003.
I coronavirus sono responsabili di diverse patologie nei mammiferi e negli uccelli, dal verificarsi di diarrea nei bovini e nei suini e a malattie respiratorie delle vie superiori nei polli. Nell'uomo, provocano infezioni delle vie respiratorie, spesso di lieve entità come il raffreddore comune, ma in rari casi potenzialmente letali come polmoniti e bronchiti.
I coronavirus sono stati responsabili delle gravi epidemie di SARS del novembre 2002, di quella della MERS del 2012 e della pandemia di COVID-19 del 2020.
Os coronavírus são um grupo de vírus de genoma de RNA simples de sentido positivo (serve diretamente para a síntese proteica), conhecidos desde meados dos anos 1960. Pertencem à subfamília taxonómica Orthocoronavirinae da família Coronaviridae, da ordem Nidovirales.[1][2]
A maioria das pessoas se infecta com os coronavírus comuns ao longo da vida. Eles são uma causa comum de infecções respiratórias brandas a moderadas de curta duração. Entre os coronavírus encontra-se o vírus causador da forma de pneumonia atípica grave conhecida por SARS,[3][4][5] e o vírus causador da COVID-19, responsável pela pandemia em 2020 e 2021.
Os coronavírus da subfamília Orthocoronaviridae se dividem em quatro gêneros: Alphacoronavirus, Betacoronavirus, Gammacoronavirus e Deltacoronavirus. De todos esses gêneros, há seis espécies que causam infecção em humanos.
No gênero Alphacoronavirus há os coronavírus humanos das espécies HCoV-229E e HCoV-NL63, que causam infecções leves a moderadas comuns.[6] Neste gênero também se encontra o CCoV, o coronavírus canino, que causa gastroenterite em cães e pode ser prevenido com vacina.[7][8]
No gênero Betacoronavirus há os coronavírus humanos das espécies HCoV-OC43, HCoV-HKU1, SARSr-CoV e MERS-CoV.
HCoV-OC43 e HCoV-HKU1 causam infecções leves a moderadas comuns. MERS-CoV causa a doença MERS (Síndrome respiratória do Médio Oriente).[6]
A espécie SARSr-CoV se divide nas cepas SARS-CoV, que causa a doença SARS (Síndrome respiratória aguda grave), e SARS-CoV-2, que causa a doença Covid-19 (COrona VIrus Disease 2019).
O SARS-CoV-2, causador da COVID-19, foi identificado em 2020, tem "parentesco" com o vírus da SARS-CoV. Causa febre, tosse e falta de ar e dificuldade para respirar (pneumonia).[9][10]
Existem sete cepas conhecidas de coronavírus humanos, e todas elas evoluíram de coronavírus de outros animais.[11]
June Almeida descobriu o primeiro coronavírus humano no St Thomas' Hospital em Londres em 1964.[12]
Foram descobertos em 2020, seis novos coronavírus em morcegos em Mianmar, mas esses vírus não estão relacionados ao Síndrome Respiratório Agudo Grave de Coronavírus (SARS CoV-1), Síndrome Respiratória do Oriente Médio (MERS) ou COVID-19.[27]
Diferentes coronavírus afetam diferentes espécies causando diferentes doenças. Os principais sintomas da COVID-19 são febre, tosse e fadiga.[28]
A transmissão do vírus pode se dar:[6]
Entre os grupos de risco estão qualquer pessoa que cuidou do paciente, incluindo profissionais de saúde ou familiares, que tenha tido contato físico com o paciente ou que tenha permanecido no mesmo local que o paciente doente.[3]
Em 2020, análises indicaram que o SARS-CoV-2 (anteriormente 2019-nCoV) pode ter passado de um animal para o ser humano.[9]
Em meados de janeiro a imprensa começou a reportar casos sobre um "misterioso vírus que causava problemas respiratórios", tendo este vírus depois sido classificado como um coronavírus e chamado numa primeira fase de 2019-nCoV. Inicialmente, 800 pessoas foram infectadas e houve 259 mortes na China, mas houve casos também no Japão, Tailândia, Coreia do Sul, França e Estados Unidos, todos associados a pessoas que haviam viajado para a China recentemente. Em 20 de janeiro a OMS estimava que o número de casos poderia estar próximo de dois mil.[9][29][30]
A 11 de março de 2020, o surto foi declarado uma pandemia, sendo que o numero de casos confirmados a nível mundial atingiu mais de 121 000, sendo em 120 diferentes territórios, dos quais mais de 80 000 na China. O número de mortes ascende a 4 300, havendo mais de 1 200 mortes fora da China.[31][32]
Um surto de MERS foi associado a um viajante que havia retornado do Oriente Médio. Quase 200 pessoas foram infectadas e houve 36 mortes.[6][33][34]
Em 2012 foi isolado outro novo coronavírus, distinto do SARS-CoV. Esse novo coronavírus, desconhecido até então, foi inicialmente identificado na Arábia Saudita e, posteriormente, em outros países do Oriente Médio, na Europa e na África. Todos os casos identificados fora da Península Arábica tinham histórico de viagem ou contato recente com viajantes procedentes de países do Oriente Médio – Arábia Saudita, Catar, Emirados Árabes e Jordânia. Pela localização dos casos, a doença passou a ser designada como síndrome respiratória do Oriente Médio, cuja sigla é MERS, do inglês “Middle East Respiratory Syndrome”. O novo vírus foi nomeado coronavírus associado à MERS (MERS-CoV).[3][6]
Os primeiros casos da síndrome respiratória aguda grave (SARS - Severe Acute Respiratory Syndrome), causada pelo SARS-CoV, aconteceram na China em 2002, tendo o vírus se espalhado rapidamente para mais de doze (12) países na América do Norte, América do Sul, Europa e Ásia. Entre 2002 e 2003, mais de oito mil (8.000) pessoas foram infectadas e cerca de oitocentas (800) morreram, no que foi chamado uma "epidemia global". (SARS-CoV).[3][9]
|coautores= (ajuda) |coautores= (ajuda) Os coronavírus são um grupo de vírus de genoma de RNA simples de sentido positivo (serve diretamente para a síntese proteica), conhecidos desde meados dos anos 1960. Pertencem à subfamília taxonómica Orthocoronavirinae da família Coronaviridae, da ordem Nidovirales.
A maioria das pessoas se infecta com os coronavírus comuns ao longo da vida. Eles são uma causa comum de infecções respiratórias brandas a moderadas de curta duração. Entre os coronavírus encontra-se o vírus causador da forma de pneumonia atípica grave conhecida por SARS, e o vírus causador da COVID-19, responsável pela pandemia em 2020 e 2021.
코로나바이러스(영어: Coronavirus, 문화어: 코로나비루스)는 코로나바이러스과(영어: Coronaviridae)의 코로나바이러스아과(Coronavirinae)에 속하는 RNA 바이러스의 총칭으로,[1][2] 사람과 동물의 호흡기와 소화기계 감염을 유발한다. 주로 점막전염(粘膜感染), 비말전파(飛沫傳播)로 쉽게 감염되며, 사람에게는 일반적으로 경미한 호흡기 감염을 일으키지만 치명적인 감염을 유발하기도 하며, 소와 돼지는 설사, 닭은 호흡기 질환이 발생하기도 한다.
현대 문명에서 치명적인 감염병을 일으키는 코로나바이러스가 많이 있다. 2003년 4월에는 중화인민공화국발 중증급성호흡기증후군, 일명 사스(SARS)가 유행해 사망률 9.6%를 기록하며 많은 사람이 사망했다. 2015년에는 중동호흡기증후군, 일명 메르스가 중동에서 전 세계로 퍼지면서 사망률 약 36%로써 사망자가 다수 발생하였다. 또한 2019년 12월부터 중국 우한발 신종 코로나바이러스 감염증(코로나19, COVID-19)이 전 세계로 확산되면서 감염자가 늘어나고 있으며, 치사율은 2020년 2월까지 집계된 자료에 따르면 2.6%로 그나마 낮은 편이지만 세계적으로 확진자가 증가하는 중이며 예방 또는 치료 목적으로 승인된 백신이나 항바이러스제는 없었다.
코로나바이러스는 니도바이러스목, 코로나바이러스과, 코로나바이러스아과 혹은 Torovirinae에 포함된 바이러스속인 종이다. 코로나바이러스는 +ssRNA와 나선형 대칭형 뉴클레오펩시드로 감싸진 바이러스다. 코로나바이러스의 유전자 크기는 거의 26에서 32 킬로베이스(kb)로 RNA바이러스 중에서 가장 크다.[3]
코로나바이러스의 이름은 왕관이나 광륜을 뜻하는 라틴어 코로나에서 유래되었고 전자현미경으로 보면 바이러스 겉부분의 가장자리가 왕관 혹은 태양의 코로나를 연상시키는 모양을 가지고 있으며, 이는 바이론의 특징을 나타낸다. 이러한 형태학적 특징은 바이러스 표면에 스파이크단백질에 의한것이다.[4]
코로나바이러스는 포지티브 센스 단일 가닥(positive-sense single-stranded) RNA 바이러스로 크기는 80–220 nm이다. 지질이 포함된 외피에 둘러싸여 있으며, 외피에 20 nm의 왕관 모양과 같은 돌기(spikes)가 있다. 코로나바이러스는 크게 4가지의 구조로 이루어져 있다. 이는 spike (S), membrane (M), envelope (E), nucleocapsid (N) proteins이다. 코로나바이러스의 스파이크 (S) 단백질은 S1과 S2 서브유닛으로 이루어져 있다. 이중에서 S1 서브유닛은 스파이크의 머리 부분이며 receptor binding domain (RBD)을 가지고 있다. S2 서브유닛은 스파이크의 기둥 부분이다. 막(M)과 외피(E) 단백질은 바이러스의 겉부분을 형성하고 형태를 유지하는데 중요한 역할을 한다. 외피 내부에는 뉴클레오캡시드(N) 단백질이 있다.[5] 몇몇 코로나바이러스(특히 베타코로나바이러스 하위집단 구성원)는 또한 항체 에스테라아제라고 불리는 단백질 같은 짧은 스파이크를 가진다
코로나바이러스는 인간에게 유발되는 일반적 감기 중 상당 부분의 원인이라고 알려져 있다. 뿐만 아니라 직접적인 바이러스성 폐렴이나 2차적인 세균성 폐렴을 일으킬 수 있으며, 직접적인 바이러스성 기관지염이나 2차적인 세균성 기관지염도 일으킬 수 있다. 2003년에 발견된 인간 코로나 바이러스는 중증급성호흡기증후군(SARS)를 일으키는 중증급성호흡기증후군 코로나바이러스(SARS-CoV)로, 상부 및 하부 호흡기 감염을 유발하는 독특한 병인을 가지고 있다. 코로나바이러스는 RNA의 유전 정보를 갖고 있는데, RNA는 변종이 쉽게 일어나서 수많은 코로나바이러스 변종이 나온다.
인간 코로나바이러스에는 7 가지 변종이 알려져있다.
코로나바이러스 HCoV-229E, -NL63, -OC43 및 -HKU1 등은 사람 사이를 지속적으로 순환하며, 전세계의 성인과 어린이에게 호흡기 감염을 일으켜 왔으며 인플루엔자 바이러스만큼이나 급속한 확산경로와 변종을 포함하는 범유행을 일으킬 것으로 과학자들은 경고하고 있다.[6] [7][8]
코로나바이러스(영어: Coronavirus, 문화어: 코로나비루스)는 코로나바이러스과(영어: Coronaviridae)의 코로나바이러스아과(Coronavirinae)에 속하는 RNA 바이러스의 총칭으로, 사람과 동물의 호흡기와 소화기계 감염을 유발한다. 주로 점막전염(粘膜感染), 비말전파(飛沫傳播)로 쉽게 감염되며, 사람에게는 일반적으로 경미한 호흡기 감염을 일으키지만 치명적인 감염을 유발하기도 하며, 소와 돼지는 설사, 닭은 호흡기 질환이 발생하기도 한다.
현대 문명에서 치명적인 감염병을 일으키는 코로나바이러스가 많이 있다. 2003년 4월에는 중화인민공화국발 중증급성호흡기증후군, 일명 사스(SARS)가 유행해 사망률 9.6%를 기록하며 많은 사람이 사망했다. 2015년에는 중동호흡기증후군, 일명 메르스가 중동에서 전 세계로 퍼지면서 사망률 약 36%로써 사망자가 다수 발생하였다. 또한 2019년 12월부터 중국 우한발 신종 코로나바이러스 감염증(코로나19, COVID-19)이 전 세계로 확산되면서 감염자가 늘어나고 있으며, 치사율은 2020년 2월까지 집계된 자료에 따르면 2.6%로 그나마 낮은 편이지만 세계적으로 확진자가 증가하는 중이며 예방 또는 치료 목적으로 승인된 백신이나 항바이러스제는 없었다.
