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Coronaviruses are a group of related RNA viruses that cause diseases in
mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
s and
bird Birds are a group of warm-blooded vertebrates constituting the class (biology), class Aves (), characterised by feathers, toothless beaked jaws, the Oviparity, laying of Eggshell, hard-shelled eggs, a high Metabolism, metabolic rate, a fou ...
s. 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 The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...
(which is also caused by other viruses, predominantly
rhinovirus The rhinovirus (from the "nose", , romanized: "of the nose", and the ) is a Positive-sense single stranded RNA virus, positive-sense, single-stranded RNA virus belonging to the genus ''Enterovirus'' in the family ''Picornaviridae''. Rhinoviru ...
es), while more lethal varieties can cause SARS, MERS and
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
. In cows and pigs they cause diarrhea, while in mice they cause
hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...
and encephalomyelitis. Coronaviruses constitute the
subfamily In biological classification, a subfamily (Latin: ', plural ') is an auxiliary (intermediate) taxonomic rank, next below family but more inclusive than genus. Standard nomenclature rules end botanical subfamily names with "-oideae", and zo ...
''Orthocoronavirinae'', in the family '' Coronaviridae'', order '' Nidovirales'' and realm ''
Riboviria ''Riboviria'' is a Realm (virology), realm of viruses that includes all viruses that use a homologous RNA-dependent polymerase for replication. It includes RNA viruses that Genetic code, encode an RNA-dependent RNA polymerase, as well as Pararnavi ...
''. They are enveloped viruses with a positive-sense single-stranded
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
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 micrograph A micrograph is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnify, magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken ...
s create an image reminiscent of the
stellar corona In astronomy, a corona (: coronas or coronae) is the outermost layer of a star's Stellar atmosphere, atmosphere. It is a hot but relatively luminosity, dim region of Plasma (physics), plasma populated by intermittent coronal structures such as so ...
, from which their name derives.


Etymology

The name "coronavirus" is derived from Latin '' corona'', meaning "crown" or "wreath", itself a borrowing from Greek ''korṓnē'', "garland, wreath". The name was coined by June Almeida and David Tyrrell who first observed and studied human coronaviruses. The word was first used in print in 1968 by an informal group of virologists in the journal ''
Nature Nature is an inherent character or constitution, particularly of the Ecosphere (planetary), ecosphere or the universe as a whole. In this general sense nature refers to the Scientific law, laws, elements and phenomenon, phenomena of the physic ...
'' to designate the new family of viruses. The name refers to the characteristic appearance of
virion A virion (plural, ''viria'' or ''virions'') is an inert virus particle capable of invading a Cell (biology), cell. Upon entering the cell, the virion disassembles and the genetic material from the virus takes control of the cell infrastructure, t ...
s (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 In astronomy, a corona (: coronas or coronae) is the outermost layer of a star's Stellar atmosphere, atmosphere. It is a hot but relatively luminosity, dim region of Plasma (physics), plasma populated by intermittent coronal structures such as so ...
or halo. This morphology is created by the viral spike peplomers, which are
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
on the surface of the virus. 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 The International Committee on Taxonomy of Viruses (ICTV) authorizes and organizes the taxonomic classification of and the nomenclature for viruses. The ICTV develops a universal taxonomic scheme for viruses, and thus has the means to appropri ...
) in 1971. As the number of new species increased, the genus was split into four genera, namely '' Alphacoronavirus'', '' Betacoronavirus'', '' Deltacoronavirus'', and '' Gammacoronavirus'' in 2009. The common name coronavirus is used to refer to any member of the subfamily ''Orthocoronavirinae''. As of 2020, 45 species are officially recognised.


History

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. Arthur Schalk and M.C. Hawn in 1931 made the first detailed report which described a new respiratory infection of chickens in
North Dakota North Dakota ( ) is a U.S. state in the Upper Midwest, named after the indigenous Dakota people, Dakota and Sioux peoples. It is bordered by the Canadian provinces of Saskatchewan and Manitoba to the north and by the U.S. states of Minneso ...
. The infection of new-born chicks was characterized by gasping and listlessness with high mortality rates of 40–90%. Leland David Bushnell and Carl Alfred Brandly isolated the virus that caused the infection in 1933. 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. 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. It was not realized at the time that these three different viruses were related. Human coronaviruses were discovered in the 1960s using two different methods in the United Kingdom and the United States. 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 The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...
virus designated B814 in 1961. The virus could not be cultivated using standard techniques which had successfully cultivated
rhinovirus The rhinovirus (from the "nose", , romanized: "of the nose", and the ) is a Positive-sense single stranded RNA virus, positive-sense, single-stranded RNA virus belonging to the genus ''Enterovirus'' in the family ''Picornaviridae''. Rhinoviru ...
es, adenoviruses and other known common cold viruses. In 1965, Tyrrell and Bynoe successfully cultivated the novel virus by serially passing it through
organ culture Organ and organs may refer to: Biology * Organ (biology), a group of tissues organized to serve a common function * Organ system, a collection of organs that function together to carry out specific functions within the body. Musical instruments ...
of human embryonic
trachea The trachea (: tracheae or tracheas), also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals' lungs. The trachea extends from ...
. The new cultivating method was introduced to the lab by Bertil Hoorn. The isolated virus when intranasally inoculated into volunteers caused a cold and was inactivated by ether which indicated it had a lipid envelope. Dorothy Hamre and John Procknow at the
University of Chicago The University of Chicago (UChicago, Chicago, or UChi) is a Private university, private research university in Chicago, Illinois, United States. Its main campus is in the Hyde Park, Chicago, Hyde Park neighborhood on Chicago's South Side, Chic ...
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. Scottish virologist June Almeida at St Thomas' Hospital in London, collaborating with Tyrrell, compared the structures of IBV, B814 and 229E in 1967. Using electron microscopy the three viruses were shown to be morphologically related by their general shape and distinctive club-like spikes. 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). Like B814, 229E, and IBV, the novel cold virus OC43 had distinctive club-like spikes when observed with the electron microscope. The IBV-like novel cold viruses were soon shown to be also morphologically related to the mouse hepatitis virus. This new group of viruses were named coronaviruses after their distinctive morphological appearance.
Human coronavirus 229E Human coronavirus 229E (HCoV-229E, ''Alphacoronavirus chicagoense'') is a species of coronavirus which infects humans and bats. It is an Viral envelope, enveloped, Sense (molecular biology), positive-sense, RNA, single-stranded RNA virus which en ...
and
human coronavirus OC43 Human coronavirus OC43 (HCoV-OC43) is a member of the species ''Betacoronavirus 1, Betacoronavirus gravedinis'', which infects humans and cattle. The infecting coronavirus is an Viral envelope, enveloped, Sense (molecular biology), positive-sense ...
continued to be studied in subsequent decades. The coronavirus strain B814 was lost. It is not known which present human coronavirus it was. 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 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...
in 2019. There have also been a large number of animal coronaviruses identified since the 1960s.''''


Microbiology


Structure

Coronaviruses are large, roughly spherical particles with unique surface projections. Their size is highly variable with average diameters of 80 to 120  nm. Extreme sizes are known from 50 to 200 nm in diameter. The total
molecular mass The molecular mass () is the mass of a given molecule, often expressed in units of daltons (Da). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The derived quan ...
is on average 40,000  kDa. They are enclosed in an envelope embedded with a number of protein molecules. The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell. The
viral envelope A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. A viral envelope protein or E protein is a protein in the en ...
is made up of a lipid bilayer in which the membrane (M), envelope (E) and spike (S) structural proteins are anchored. The molar ratio of E:S:M in the lipid bilayer is approximately 1:20:300. The E and M protein are the structural proteins that combined with the lipid bilayer to shape the viral envelope and maintain its size. S proteins are needed for interaction with the host cells. But
human coronavirus NL63 Human coronavirus NL63 (HCoV-NL63, ''Alphacoronavirus amsterdamense'') is a species of coronavirus, assigned to the subgenus ''Setracovirus'' and the genus ''Alphacoronavirus''. It was identified in late 2004 in patients in Netherlands, the Nethe ...
is peculiar in that its M protein has the binding site for the host cell, and not its S protein. 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). 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 Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
residues and forms a layer 7.8 nm thick. It has three domains, a short N-terminal
ectodomain An ectodomain is the domain of a membrane protein that extends into the extracellular space (the space outside a cell). Ectodomains are usually the parts of proteins that initiate contact with surfaces, which leads to signal transduction. A n ...
, 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
glycan The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate ...
s in their protein amino-terminal domain. The M protein is crucial during the assembly, budding, envelope formation, and pathogenesis stages of the virus lifecycle. The E proteins are minor structural proteins and highly variable in different species. There are only about 20 copies of the E protein molecule in a coronavirus particle. They are 8.4 to 12 kDa in size and are composed of 76 to 109 amino acids. 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 channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...
s in the lipid bilayer. They are responsible for virion assembly, intracellular trafficking and morphogenesis (budding). 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. Each spike is about 20 nm long and is composed of a trimer of the Sprotein. The S protein is in turn composed of an S1 and S2 subunit. The homotrimeric Sprotein 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. 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. 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). A subset of coronaviruses (specifically the members of betacoronavirus subgroup A) also has a shorter spike-like surface protein called
hemagglutinin esterase Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as an invading mechanism. HEs helps in the attachment and destruction of certain sialic acid receptors that are found on the host cell surface. V ...
(HE). 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. 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 Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
genome in a continuous beads-on-a-string type conformation. 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
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
s 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.


Genome

Coronaviruses contain a positive-sense, single-stranded RNA genome. The genome size for coronaviruses ranges from 26.4 to 31.7 kilobases. The genome size is one of the largest among RNA viruses. The genome has a 5′ methylated cap and a 3′ polyadenylated tail. 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). The later reading frames encode the four major structural proteins: spike, envelope, membrane, and nucleocapsid. 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.


Replication cycle


Cell entry

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. Coronaviruses can enter cells by either fusing to their lipid envelope with the cell membrane on the cell surface or by internalization via endocytosis. Insertion of a cleavage site can boost viral entry in different cell types by enabling promiscuous cleavage of the spike when contacting different proteases.


Genome translation

On entry into the host cell, the virus particle is uncoated, and its
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
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. 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. The ribosomal frameshift allows for the continuous translation of ORF1a followed by ORF1b. 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).


Replicase-transcriptase

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. ''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. ''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. The subgenomic mRNAs form a " nested set" which have a common 5'-head and partially duplicate 3'-end. ''Recombination'' – The replicase-transcriptase complex is also capable of
genetic recombination Genetic recombination (also known as genetic reshuffling) is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryot ...
when at least two viral genomes are present in the same infected cell. 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. The exact mechanism of recombination in coronaviruses is unclear, but likely involves template switching during genome replication.


Assembly and release

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. RNA translation occurs inside the
endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
. The viral structural proteins S, E, and M move along the secretory pathway into the Golgi intermediate compartment. There, the Mproteins 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.


Transmission

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. Coronaviruses mainly target epithelial cells.'''' They are transmitted from one host to another host, depending on the coronavirus species, by either an
aerosol An aerosol is a suspension (chemistry), suspension of fine solid particles or liquid Drop (liquid), droplets in air or another gas. Aerosols can be generated from natural or Human impact on the environment, human causes. The term ''aerosol'' co ...
,
fomite A fomite () or fomes () is any inanimate object that, when contaminated with or exposed to infectious agents (such as pathogenic bacteria, viruses or fungi), can transfer disease to a new host. Transfer of pathogens by fomites A fomite is any ...
, or fecal-oral route. Human coronaviruses infect the epithelial cells of the respiratory tract, while animal coronaviruses generally infect the epithelial cells of the digestive tract.'''' SARS coronavirus, for example, infects the human epithelial cells of the lungs via an aerosol route by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Transmissible gastroenteritis coronavirus (TGEV) infects the pig epithelial cells of the digestive tract via a fecal–oral route by binding to the alanine aminopeptidase (APN) receptor.


Classification

Coronaviruses form the subfamily ''Orthocoronavirinae,'' which is one of two subfamilies in the family '' Coronaviridae,'' order '' Nidovirales,'' and realm ''
Riboviria ''Riboviria'' is a Realm (virology), realm of viruses that includes all viruses that use a homologous RNA-dependent polymerase for replication. It includes RNA viruses that Genetic code, encode an RNA-dependent RNA polymerase, as well as Pararnavi ...
.'' They are divided into the four genera: ''Alphacoronavirus'', ''Betacoronavirus'', ''Gammacoronavirus'' and ''Deltacoronavirus''. Alphacoronaviruses and betacoronaviruses infect mammals, while gammacoronaviruses and deltacoronaviruses primarily infect birds.' * Genus: '' Alphacoronavirus''; ** Species: '' Alphacoronavirus 1'' ( TGEV, Feline coronavirus, Canine coronavirus), ''
Human coronavirus 229E Human coronavirus 229E (HCoV-229E, ''Alphacoronavirus chicagoense'') is a species of coronavirus which infects humans and bats. It is an Viral envelope, enveloped, Sense (molecular biology), positive-sense, RNA, single-stranded RNA virus which en ...
'', ''
Human coronavirus NL63 Human coronavirus NL63 (HCoV-NL63, ''Alphacoronavirus amsterdamense'') is a species of coronavirus, assigned to the subgenus ''Setracovirus'' and the genus ''Alphacoronavirus''. It was identified in late 2004 in patients in Netherlands, the Nethe ...
'', '' Miniopterus bat coronavirus 1'', '' Miniopterus bat coronavirus HKU8'', '' Porcine epidemic diarrhea virus'', '' Rhinolophus bat coronavirus HKU2'', '' Scotophilus bat coronavirus 512'' * Genus '' Betacoronavirus''; ** Species: '' Betacoronavirus 1'' ( ''Bovine Coronavirus'', ''
Human coronavirus OC43 Human coronavirus OC43 (HCoV-OC43) is a member of the species ''Betacoronavirus 1, Betacoronavirus gravedinis'', which infects humans and cattle. The infecting coronavirus is an Viral envelope, enveloped, Sense (molecular biology), positive-sense ...
''), '' Hedgehog coronavirus 1,'' ''
Human coronavirus HKU1 Human coronavirus HKU1 (HCoV-HKU1, ''Betacoronavirus hongkonense'') is a species of coronavirus in humans and animals. It causes an upper respiratory disease with symptoms of the common cold, but can advance to pneumonia and bronchiolitis. It was ...
'', '' Middle East respiratory syndrome-related coronavirus,'' '' Murine coronavirus'', '' Pipistrellus bat coronavirus HKU5'', '' Rousettus bat coronavirus HKU9'', '' Severe acute respiratory syndrome–related coronavirus'' ('' SARS-CoV-1'', ''
SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...
''), '' Tylonycteris bat coronavirus HKU4'' * Genus '' Gammacoronavirus''; ** Species: '' Avian coronavirus,'' '' Beluga whale coronavirus SW1'' * Genus '' Deltacoronavirus'' ** Species: '' Bulbul coronavirus HKU11'', ''Porcine'' ''coronavirus HKU15''


Origin

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. 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 betacoronavirusand 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. Many human coronaviruses have their origin in bats. The human coronavirus NL63 shared a common ancestor with a bat coronavirus (ARCoV.2) between 1190 and 1449 CE. The human coronavirus 229E shared a common ancestor with a bat coronavirus (GhanaGrp1 Bt CoV) between 1686 and 1800 CE. More recently, alpaca coronavirus and human coronavirus 229E diverged sometime before 1960. MERS-CoV emerged in humans from bats through the intermediate host of camels. MERS-CoV, although related to several bat coronavirus species, appears to have diverged from these several centuries ago. The most closely related bat coronavirus and SARS-CoV diverged in 1986. The ancestors of SARS-CoV first infected leaf-nose bats of the genus ''
Hipposideridae The Hipposideridae are a family (biology), family of bats commonly known as the Old World leaf-nosed bats. While it has often been seen as a subfamily, Hipposiderinae, of the family Rhinolophidae, it is now more generally classified as its own fa ...
''; subsequently, they spread to horseshoe bats in the species '' Rhinolophidae'', then to Asian palm civets, and finally to humans. Unlike other betacoronaviruses, bovine coronavirus of the species '' Betacoronavirus 1'' and subgenus '' Embecovirus'' is thought to have originated in
rodent Rodents (from Latin , 'to gnaw') are mammals of the Order (biology), order Rodentia ( ), which are characterized by a single pair of continuously growing incisors in each of the upper and Mandible, lower jaws. About 40% of all mammal specie ...
s and not in bats. In the 1790s, equine coronavirus diverged from the bovine coronavirus after a cross-species jump. Later in the 1890s, human coronavirus OC43 diverged from bovine coronavirus after another cross-species spillover event. 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. Besides causing respiratory infections, human coronavirus OC43 is also suspected of playing a role in neurological diseases. In the 1950s, the human coronavirus OC43 began to diverge into its present
genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
s. Phylogenetically, mouse hepatitis virus ('' Murine coronavirus''), which infects the mouse's liver and
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
, is related to human coronavirus OC43 and bovine coronavirus. Human coronavirus HKU1, like the aforementioned viruses, also has its origins in rodents.


Infection in humans

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. Coronaviruses can cause colds with major symptoms, such as fever, and a
sore throat Sore throat, also known as throat pain, is pain or irritation of the throat. The majority of sore throats are caused by a virus, for which antibiotics are not helpful. For sore throat caused by bacteria (GAS), treatment with antibiotics may hel ...
from swollen adenoids. Coronaviruses can cause pneumonia (either direct viral pneumonia or secondary bacterial pneumonia) and
bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...
(either direct viral bronchitis or secondary bacterial bronchitis). 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. 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: #
Human coronavirus OC43 Human coronavirus OC43 (HCoV-OC43) is a member of the species ''Betacoronavirus 1, Betacoronavirus gravedinis'', which infects humans and cattle. The infecting coronavirus is an Viral envelope, enveloped, Sense (molecular biology), positive-sense ...
(HCoV-OC43), β-CoV #
Human coronavirus HKU1 Human coronavirus HKU1 (HCoV-HKU1, ''Betacoronavirus hongkonense'') is a species of coronavirus in humans and animals. It causes an upper respiratory disease with symptoms of the common cold, but can advance to pneumonia and bronchiolitis. It was ...
(HCoV-HKU1), β-CoV #
Human coronavirus 229E Human coronavirus 229E (HCoV-229E, ''Alphacoronavirus chicagoense'') is a species of coronavirus which infects humans and bats. It is an Viral envelope, enveloped, Sense (molecular biology), positive-sense, RNA, single-stranded RNA virus which en ...
(HCoV-229E), α-CoV #
Human coronavirus NL63 Human coronavirus NL63 (HCoV-NL63, ''Alphacoronavirus amsterdamense'') is a species of coronavirus, assigned to the subgenus ''Setracovirus'' and the genus ''Alphacoronavirus''. It was identified in late 2004 in patients in Netherlands, the Nethe ...
(HCoV-NL63), α-CoV– Three human coronaviruses produce potentially severe symptoms: # Severe acute respiratory syndrome coronavirus (SARS-CoV), β-CoV (identified in 2003) # Middle East respiratory syndrome-related coronavirus (MERS-CoV), β-CoV (identified in 2012) # Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), β-CoV (identified in 2019) These cause the diseases commonly called SARS, MERS, and
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
respectively.


Common cold

Although the
common cold The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...
is usually caused by
rhinovirus The rhinovirus (from the "nose", , romanized: "of the nose", and the ) is a Positive-sense single stranded RNA virus, positive-sense, single-stranded RNA virus belonging to the genus ''Enterovirus'' in the family ''Picornaviridae''. Rhinoviru ...
es, in about 15% of cases the cause is a coronavirus. 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. The four mild coronaviruses have a seasonal incidence occurring in the winter months in temperate climates. There is no preponderance in any season in
tropical climate Tropical climate is the first of the five major climate groups in the Köppen climate classification identified with the letter A. Tropical climates are defined by a monthly average temperature of or higher in the coolest month, featuring hot te ...
s.


Severe acute respiratory syndrome (SARS)

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 The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
(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.


Middle East respiratory syndrome (MERS)

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). The World Health Organization issued a global alert soon after. The WHO update on 28 September 2012 said the virus did not seem to pass easily from person to person. 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.''Nouveau coronavirus—Point de situation : Un nouveau cas d'infection confirmé''
''(Novel coronavirus—Status report: A new case of confirmed infection)'' 12 May 2013, social-sante.gouv.fr
In addition, cases of human-to-human transmission were reported by the Ministry of Health in
Tunisia Tunisia, officially the Republic of Tunisia, is a country in the Maghreb region of North Africa. It is bordered by Algeria to the west and southwest, Libya to the southeast, and the Mediterranean Sea to the north and east. Tunisia also shares m ...
. 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. By 30 October 2013, there were 124 cases and 52 deaths in Saudi Arabia. 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. In May 2015, an outbreak of MERS-CoV occurred in the
Republic of Korea South Korea, officially the Republic of Korea (ROK), is a country in East Asia. It constitutes the southern half of the Korea, Korean Peninsula and borders North Korea along the Korean Demilitarized Zone, with the Yellow Sea to the west and t ...
, 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. 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 Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular Statistical population, population, scaled to the size of that population, per unit of time. Mortality rate is typically ...
of approximately 34.5%.


Coronavirus disease 2019 (COVID-19)

In December 2019, a pneumonia outbreak was reported in
Wuhan Wuhan; is the capital of Hubei, China. With a population of over eleven million, it is the most populous city in Hubei and the List of cities in China by population, eighth-most-populous city in China. It is also one of the nine National cent ...
, China. On 31 December 2019, the outbreak was traced to a novel strain of coronavirus, which was given the interim name 2019-nCoV by the World Health Organization, later renamed
SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...
by the
International Committee on Taxonomy of Viruses The International Committee on Taxonomy of Viruses (ICTV) authorizes and organizes the taxonomic classification of and the nomenclature for viruses. The ICTV develops a universal taxonomic scheme for viruses, and thus has the means to appropri ...
. As of , there were at least confirmed deaths and more than confirmed cases in the
COVID-19 pandemic The COVID-19 pandemic (also known as the coronavirus pandemic and COVID pandemic), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began with an disease outbreak, outbreak of COVID-19 in Wuhan, China, in December ...
. The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with approximately 70% genetic similarity to the SARS-CoV. The virus has a 96% similarity to a bat coronavirus, so it is widely suspected to originate from bats as well.


Coronavirus HuPn-2018

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.


Infection in animals

Coronaviruses have been recognized as causing pathological conditions in
veterinary medicine Veterinary medicine is the branch of medicine that deals with the prevention, management, medical diagnosis, diagnosis, and treatment of disease, disorder, and injury in non-human animals. The scope of veterinary medicine is wide, covering all a ...
since the 1930s. They infect a range of animals including swine, cattle, horses, camels, cats, dogs, rodents, birds and bats. The majority of animal related coronaviruses infect the intestinal tract and are transmitted by a fecal-oral route. Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.


Farm animals

Coronaviruses infect domesticated birds. Infectious bronchitis virus (IBV), a type of coronavirus, causes avian infectious bronchitis. The virus is of concern to the poultry industry because of the high mortality from infection, its rapid spread, and its effect on production. The virus affects both meat production and egg production and causes substantial economic loss. 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. The virus is transmitted by aerosol and food contaminated by feces. Different
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
s against IBV exist and have helped to limit the spread of the virus and its variants. Infectious bronchitis virus is one of a number of strains of the species '' Avian coronavirus''. Another strain of avian coronavirus is turkey coronavirus (TCV) which causes enteritis in turkeys. Coronaviruses also affect other branches of
animal husbandry Animal husbandry is the branch of agriculture concerned with animals that are raised for meat, animal fiber, fibre, milk, or other products. It includes day-to-day care, management, production, nutrition, selective breeding, and the raising ...
such as
pig farming Pig farming, pork farming, pig production or hog farming is the raising and breeding of domestic pigs as livestock, and is a branch of animal husbandry. Pigs are farmed principally for food (e.g. pork: bacon, ham, gammon (meat), gammon) and l ...
and cattle raising. Swine acute diarrhea syndrome coronavirus (SADS-CoV), which is related to bat coronavirus HKU2, causes diarrhea in pigs. Porcine epidemic diarrhea virus (PEDV) is a coronavirus that has recently emerged and similarly causes diarrhea in pigs. Transmissible gastroenteritis virus (TGEV), which is a member of the species ''Alphacoronavirus 1'', is another coronavirus that causes diarrhea in young pigs. In the cattle industry bovine coronavirus (BCV), which is a member of the species '' Betacoronavirus 1'' and related to HCoV-OC43, is responsible for severe profuse enteritis in young calves.


Domestic pets

Coronaviruses infect domestic pets such as cats, dogs, and ferrets. There are two forms of feline coronavirus which are both members of the species ''Alphacoronavirus 1''. Feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
of this virus can result in feline infectious peritonitis (FIP), a disease with high mortality. There are two different coronaviruses that infect dogs. Canine coronavirus (CCoV), which is a member of the species ''Alphacoronavirus 1'', causes mild gastrointestinal disease. Canine respiratory coronavirus (CRCoV), which is a member of the species '' Betacoronavirus 1'' and related to HCoV-OC43, cause respiratory disease. Similarly, there are two types of coronavirus that infect ferrets. 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).


Laboratory animals

Coronaviruses infect laboratory animals. Mouse hepatitis virus (MHV), which is a member of the species '' Murine coronavirus'', causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice. Prior to the discovery of SARS-CoV, MHV was the best-studied coronavirus both '' in vivo'' and ''
in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
'' 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 Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...
. Sialodacryoadenitis virus (SDAV), which is a strain of the species ''Murine coronavirus'', 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. Mortality rates are high.


Prevention and treatment

A number of vaccines using different methods have been developed against human coronavirus SARS-CoV-2. 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. 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.


See also

* Coronavirus diseases * Zoonosis


References


Further reading

* * * * * {{Portal bar, COVID-19, Medicine, Viruses Animal virology Virus subfamilies