Coronaviruses are a group of related
RNA viruses that cause diseases in
mammals and birds. In humans and birds, they cause
respiratory tract infection
Respiratory tract infections (RTIs) are infectious diseases involving the respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tract infection (LRI ...
s 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
rhinovirus
The rhinovirus (from the grc, ῥίς, rhis "nose", , romanized: "of the nose", and the la, vīrus) is the most common viral infectious agent in humans and is the predominant cause of the common cold. Rhinovirus infection proliferates in tem ...
es), while more lethal varieties can cause
SARS
Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species, ''seve ...
,
MERS
Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by ''Middle East respiratory syndrome–related coronavirus'' (MERS-CoV). Symptoms may range from none, to mild, to severe. Typical symptoms include fever, cough, ...
and
COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickly ...
, which is causing the
ongoing pandemic. In cows and pigs they cause
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
, while in mice they cause
hepatitis
Hepatitis is inflammation of the 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), poor appetite, vomiting, tiredness, abdominal ...
and
encephalomyelitis
Encephalomyelitis is inflammation of the brain and spinal cord. Various types of encephalomyelitis include:
* '' Acute disseminated encephalomyelitis'' or ''postinfectious encephalomyelitis'', a demyelinating disease of the brain and spinal cord, ...
.
Coronaviruses constitute the
subfamily ''Orthocoronavirinae'', in the family ''
Coronaviridae
''Coronaviridae'' is a family of enveloped, positive-strand RNA viruses which infect amphibians, birds, and mammals. The group includes the subfamilies '' Letovirinae'' and ''Orthocoronavirinae;'' the members of the latter are known as coronavi ...
'', order ''
Nidovirales'' and realm ''
Riboviria''.
They are
enveloped virus
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.
Numerous human pathogenic viruses in circulation are encase ...
es with a
positive-sense single-stranded RNA genome
In the fields of molecular biology and genetics, 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 g ...
and a
nucleocapsid of helical symmetry. The
genome size
Genome size is the total amount of DNA contained within one copy of a single complete genome. It is typically measured in terms of mass in picograms (trillionths (10−12) of a gram, abbreviated pg) or less frequently in daltons, or as the total ...
of coronaviruses ranges from approximately 26 to 32
kilobase
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DN ...
s, one of the largest among RNA viruses.
They have characteristic club-shaped
spikes
The SPIKES protocol is a method used in clinical medicine to break bad news to patients and families. As receiving bad news can cause distress and anxiety, clinicians need to deliver the news carefully. By using the SPIKES method for introducing a ...
that project from their surface, which in
electron micrograph
A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken on a mi ...
s create an image reminiscent of the
stellar corona, from which their name derives.
Etymology
The name "coronavirus" is derived from Latin ''
corona
Corona (from the Latin for 'crown') most commonly refers to:
* Stellar corona, the outer atmosphere of the Sun or another star
* Corona (beer), a Mexican beer
* Corona, informal term for the coronavirus SARS-CoV-2, which causes the COVID-19 di ...
'', meaning "crown" or "wreath", itself a borrowing from
Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
''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, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are ...
'' to designate the new family of viruses.
The name refers to the characteristic appearance of
virion
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's ...
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
A corona ( coronas or coronae) is the outermost layer of a star's atmosphere. It consists of plasma.
The Sun's corona lies above the chromosphere and extends millions of kilometres into outer space. It is most easily seen during a total solar ...
or halo.
This
morphology
Morphology, from the Greek and meaning "study of shape", may refer to:
Disciplines
* Morphology (archaeology), study of the shapes or forms of artifacts
* Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies ...
is created by the viral spike
peplomer
In virology, a spike protein or peplomer protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an enveloped virus. as cited in The proteins are usually glycoproteins that form dimers o ...
s, which are
proteins 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 nomenclatures for viruses. The ICTV has developed a universal taxonomic scheme for viruses, and thus has the means to ap ...
) in 1971.
As the number of new species increased, the genus was split into four genera, namely ''
Alphacoronavirus
Alphacoronaviruses (Alpha-CoV) are members of the first of the four genera (''Alpha''-, '' Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. They are positive-sense, single-stranded RNA viruses that infect mammals, including humans. They ...
'', ''
Betacoronavirus
''Betacoronavirus'' (β-CoVs or Beta-CoVs) is one of four genera (''Alpha''-, ''Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. Member viruses are enveloped, positive-strand RNA viruses that infect mammals (of which humans are part). ...
'', ''
Deltacoronavirus
''Deltacoronavirus'' (Delta-CoV) is one of the four genera ('' Alpha-'', '' Beta-'', '' Gamma-'', and ''Delta-'') of coronaviruses. It is in the subfamily ''Orthocoronavirinae'' of the family ''Coronaviridae''. They are enveloped, positive-se ...
'', and ''
Gammacoronavirus
''Gammacoronavirus'' (Gamma-CoV) is one of the four genera (''Alpha''-, '' Beta-'', ''Gamma-'', and '' Delta-'') of coronaviruses. It is in the subfamily ''Orthocoronavirinae'' of the family ''Coronaviridae''. They are enveloped, positive-sens ...
'' 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 Sioux. North Dakota is bordered by the Canadian provinces of Saskatchewan and Manitoba to the north and by the U.S. states of Minnesota to the east, So ...
. 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
''Avian coronavirus'' is a species of virus from the genus '' Gammacoronavirus'' that infects birds; since 2018, all gammacoronaviruses which infect birds have been classified as this single species. The strain of avian coronavirus previously kn ...
(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
Murine coronavirus (M-CoV) is a virus in the genus ''Betacoronavirus'' that infects mice. Belonging to the subgenus ''Embecovirus'', murine coronavirus strains are enterotropic or polytropic. Enterotropic strains include mouse hepatitis virus (M ...
(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 virus designated B814 in 1961.
The virus could not be cultivated using standard techniques which had successfully cultivated
rhinovirus
The rhinovirus (from the grc, ῥίς, rhis "nose", , romanized: "of the nose", and the la, vīrus) is the most common viral infectious agent in humans and is the predominant cause of the common cold. Rhinovirus infection proliferates in tem ...
es,
adenoviruses
Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...
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
The trachea, 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 air- breathing animals with lungs. The trachea extends from the ...
. 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
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be ...
which indicated it had a
lipid envelope.
Dorothy Hamre and John Procknow at the
University of Chicago
The University of Chicago (UChicago, Chicago, U of C, or UChi) is a private university, private research university in Chicago, Illinois. Its main campus is located in Chicago's Hyde Park, Chicago, Hyde Park neighborhood. The University of Chic ...
isolated a novel cold from medical students in 1962. They isolated and grew the virus in kidney
tissue culture
Tissue culture is the growth of tissues or cells in an artificial medium separate from the parent organism. This technique is also called micropropagation. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, su ...
, 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
The SPIKES protocol is a method used in clinical medicine to break bad news to patients and families. As receiving bad news can cause distress and anxiety, clinicians need to deliver the news carefully. By using the SPIKES method for introducing a ...
. A research group at the
National Institute of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
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'') is a species of coronavirus which infects humans and bats. It is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the APN receptor. Along with Human c ...
and
human coronavirus OC43
Human coronavirus OC43 (HCoV-OC43) is a member of the species '' Betacoronavirus 1'', which infects humans and cattle. The infecting coronavirus is an enveloped, positive-sense, single-stranded RNA virus that enters its host cell by binding to ...
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
Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for ...
in 2003,
HCoV NL63 in 2003,
HCoV HKU1 in 2004,
MERS-CoV
''Middle East respiratory syndrome–related coronavirus'' (''MERS-CoV''), or EMC/2012 ( HCoV-EMC/2012), is the virus that causes Middle East respiratory syndrome (MERS). It is a species of coronavirus which infects humans, bats, and camels. Th ...
in 2013, and
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
in 2019. There have also been a large number of animal coronaviruses identified since the 1960s.''
''
Microbiology
Structure
![Vaccines-08-00587-g002-A](https://upload.wikimedia.org/wikipedia/commons/7/79/Vaccines-08-00587-g002-A.png)
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 (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quanti ...
is on average 40,000
kDa
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
. 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.
Numerous human pathogenic viruses in circulation are encase ...
is made up of a
lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
in which the
membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...
(M),
envelope
An envelope is a common packaging item, usually made of thin, flat material. It is designed to contain a flat object, such as a letter or card.
Traditional envelopes are made from sheets of paper cut to one of three shapes: a rhombus, a sh ...
(E) and
spike
Spike, spikes, or spiking may refer to:
Arts, entertainment, and media
Books
* ''The Spike'' (novel), a novel by Arnaud de Borchgrave
* ''The Spike'' (book), a nonfiction book by Damien Broderick
* ''The Spike'', a starship in Peter F. Hamilto ...
(S)
structural 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, respond ...
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
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, an ...
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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha 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 notable ...
, a triple-spanning
transmembrane domain
A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bi ...
, and a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
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
Budding or blastogenesis is a type of asexual reproduction in which a new organism develops from an outgrowth or bud due to cell division at one particular site. For example, the small bulb-like projection coming out from the yeast cell is kno ...
, 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 channels in the lipid bilayer. They are responsible for virion assembly,
intracellular trafficking and morphogenesis (budding).
![SARS-CoV MERS-CoV genome organization and S-protein domains](https://upload.wikimedia.org/wikipedia/commons/1/11/SARS-CoV_MERS-CoV_genome_organization_and_S-protein_domains.png)
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
Spike, spikes, or spiking may refer to:
Arts, entertainment, and media
Books
* ''The Spike'' (novel), a novel by Arnaud de Borchgrave
* ''The Spike'' (book), a nonfiction book by Damien Broderick
* ''The Spike'', a starship in Peter F. Hamilto ...
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
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a recept ...
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
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...
such as
cathepsin
Cathepsins (Ancient Greek ''kata-'' "down" and ''hepsein'' "boil"; abbreviated CTS) are proteases (enzymes that degrade proteins) found in all animals as well as other organisms. There are approximately a dozen members of this family, which are di ...
family and
transmembrane protease serine 2 (TMPRSS2) of the host cell.
![15010_2020_1486_Fig3_HTML](https://upload.wikimedia.org/wikipedia/commons/d/d2/15010_2020_1486_Fig3_HTML.webp)
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
Carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein) (CEACAM1) also known as CD66a (Cluster of Differentiation 66a), is a human glycoprotein, and a member of the carcinoembryonic antigen (CEA) gene family.
Function
...
(CEACAM1). S1-CTDs are responsible for recognizing different protein receptors such as
angiotensin-converting enzyme 2
Angiotensin-converting enzyme 2 (ACE2) is an enzyme that can be found either attached to the membrane of cells (mACE2) in the intestines, kidney, testis, gallbladder, and heart or in a soluble form (sACE2). Both membrane bound and soluble ACE2 a ...
(ACE2),
aminopeptidase N (APN), and
dipeptidyl peptidase 4 (DPP4).
A subset of coronaviruses (specifically the members of
betacoronavirus
''Betacoronavirus'' (β-CoVs or Beta-CoVs) is one of four genera (''Alpha''-, ''Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. Member viruses are enveloped, positive-strand RNA viruses that infect mammals (of which humans are part). ...
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. Vi ...
(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 genome in a continuous
Bead
A bead is a small, decorative object that is formed in a variety of shapes and sizes of a material such as stone, bone, shell, glass, plastic, wood, or pearl and with a small hole for threading or stringing. Beads range in size from under ...
s-on-a-string type conformation.
N protein is a
phosphoprotein
A phosphoprotein is a protein that is posttranslationally modified by the attachment of either a single phosphate group, or a complex molecule such as 5'-phospho-DNA, through a phosphate group. The target amino acid is most often serine, threonin ...
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.
Genome
![SARS Coronavirus Genome Organization](https://upload.wikimedia.org/wikipedia/commons/0/0d/SARS_Coronavirus_Genome_Organization.png)
Coronaviruses contain a
positive-sense, single-stranded RNA genome. The
genome size
Genome size is the total amount of DNA contained within one copy of a single complete genome. It is typically measured in terms of mass in picograms (trillionths (10−12) of a gram, abbreviated pg) or less frequently in daltons, or as the total ...
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 frame
In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
s 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
Spike, spikes, or spiking may refer to:
Arts, entertainment, and media
Books
* ''The Spike'' (novel), a novel by Arnaud de Borchgrave
* ''The Spike'' (book), a nonfiction book by Damien Broderick
* ''The Spike'', a starship in Peter F. Hamilto ...
,
envelope
An envelope is a common packaging item, usually made of thin, flat material. It is designed to contain a flat object, such as a letter or card.
Traditional envelopes are made from sheets of paper cut to one of three shapes: a rhombus, a sh ...
,
membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...
, 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
![coronavirus replication](https://upload.wikimedia.org/wikipedia/commons/f/f4/Coronavirus_replication.png)
Infection begins when the viral spike protein attaches to its complementary host cell receptor. After attachment, a
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
of the host cell
cleaves Cleaves is a surname. Notable people with the surname include:
* Henry B. Cleaves
*Jessica Cleaves (1948–2014), American singer-songwriter
*Margaret Cleaves (1848–1917), American physician
*Mateen Cleaves (born 1977), American basketball player ...
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.
Genome translation
On entry into the
host cell
In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
, the virus particle is
uncoated, and its
genome
In the fields of molecular biology and genetics, 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 g ...
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
In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
ORF1a
ORF1ab (also ORF1a/b) refers collectively to two open reading frames (ORFs), ORF1a and ORF1b, that are conserved in the genomes of nidoviruses, a group of viruses that includes coronaviruses. The genes express large polyproteins that undergo pr ...
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
A slippery sequence is a small section of codon nucleotide sequences (usually UUUAAAC) that controls the rate and chance of ribosomal frameshifting. A slippery sequence causes a faster ribosomal transfer which in turn can cause the reading ribosom ...
(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
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...
,
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
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separati ...
(nsp13), and
exoribonuclease
An exoribonuclease is an exonuclease ribonuclease, which are enzymes that degrade RNA by removing terminal nucleotides from either the 5' end or the 3' end of the RNA molecule. Enzymes that remove nucleotides from the 5' end are called ''5'-3 ...
(nsp14).
Replicase-transcriptase
![Replication-transcription complex for Coronaviruses cropped](https://upload.wikimedia.org/wikipedia/commons/f/fd/Replication-transcription_complex_for_Coronaviruses_cropped.png)
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
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process. The
exoribonuclease
An exoribonuclease is an exonuclease ribonuclease, which are enzymes that degrade RNA by removing terminal nucleotides from either the 5' end or the 3' end of the RNA molecule. Enzymes that remove nucleotides from the 5' end are called ''5'-3 ...
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.
![Nested subgenomic RNA](https://upload.wikimedia.org/wikipedia/commons/5/59/Nested_subgenomic_RNA.jpg)
''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 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 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
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a recept ...
is central in determining the
tissue tropism
Tissue tropism is the range of cells and tissues of a host that support growth of a particular pathogen, such as a virus, bacterium or parasite.
Some bacteria and viruses have a broad tissue tropism and can infect many types of cells and tissues. ...
,
infectivity
In epidemiology, infectivity is the ability of a pathogen to establish an infection. More specifically, infectivity is a pathogen's capacity for horizontal transmission — that is, how frequently it spreads among hosts that are not in a parent ...
, and
species range of the released virus. Coronaviruses mainly target
epithelial cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
.''
'' They are transmitted from one host to another host, depending on the coronavirus species, by either an
aerosol,
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
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
.''
''
SARS coronavirus
Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for th ...
, for example, infects the human epithelial cells of the lungs via an aerosol route
by binding to the
angiotensin-converting enzyme 2
Angiotensin-converting enzyme 2 (ACE2) is an enzyme that can be found either attached to the membrane of cells (mACE2) in the intestines, kidney, testis, gallbladder, and heart or in a soluble form (sACE2). Both membrane bound and soluble ACE2 a ...
(ACE2) receptor.
Transmissible gastroenteritis coronavirus
Transmissible gastroenteritis virus or Transmissible gastroenteritis coronavirus (TGEV) is a coronavirus which infects pigs. It is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the APN recep ...
(TGEV) infects the pig epithelial cells of the digestive tract via a fecal-oral route
by binding to the
Alanine aminopeptidase (APN) receptor.
Classification
![Phylogenetic tree of coronaviruses](https://upload.wikimedia.org/wikipedia/commons/d/dd/Phylogenetic_tree_of_coronaviruses.jpg)
Coronaviruses form the subfamily ''Orthocoronavirinae,''
which is one of two sub-families in the family ''
Coronaviridae
''Coronaviridae'' is a family of enveloped, positive-strand RNA viruses which infect amphibians, birds, and mammals. The group includes the subfamilies '' Letovirinae'' and ''Orthocoronavirinae;'' the members of the latter are known as coronavi ...
,'' order ''
Nidovirales,'' and realm ''
Riboviria.
'' 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
Alphacoronaviruses (Alpha-CoV) are members of the first of the four genera (''Alpha''-, '' Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. They are positive-sense, single-stranded RNA viruses that infect mammals, including humans. They ...
'';
** Species: ''
Alphacoronavirus 1'' (
TGEV,
Feline coronavirus
Feline coronavirus (FCoV) is a positive-stranded RNA virus that infects cats worldwide. It is a coronavirus of the species '' Alphacoronavirus 1'' which includes canine coronavirus (CCoV) and porcine transmissible gastroenteritis coronavirus (T ...
,
Canine coronavirus
Canine coronavirus (CCoV) is an enveloped, positive-sense, single-stranded RNA virus which is a member of the species ''Alphacoronavirus 1.'' It causes a highly contagious intestinal disease worldwide in dogs. The infecting virus enters its ho ...
), ''
Human coronavirus 229E
''Human coronavirus 229E'' (''HCoV-229E'') is a species of coronavirus which infects humans and bats. It is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the APN receptor. Along with Human c ...
'', ''
Human coronavirus NL63
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, an ...
'', ''
Miniopterus bat coronavirus 1'', ''
Miniopterus bat coronavirus HKU8'', ''
Porcine epidemic diarrhea virus
''Porcine epidemic diarrhea virus'' (PED virus or PEDV) is a coronavirus that infects the cells lining the small intestine of a pig, causing porcine epidemic diarrhoea, a condition of severe diarrhea and dehydration. Older hogs mostly get sick ...
'', ''
Rhinolophus bat coronavirus HKU2'', ''
Scotophilus bat coronavirus 512''
* Genus ''
Betacoronavirus
''Betacoronavirus'' (β-CoVs or Beta-CoVs) is one of four genera (''Alpha''-, ''Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. Member viruses are enveloped, positive-strand RNA viruses that infect mammals (of which humans are part). ...
'';
** Species: ''
Betacoronavirus 1
''Betacoronavirus 1'' is a species of coronavirus which infects humans and cattle. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus and is a member of the genus ''Betacoronavirus'' and subgenus ''Embecovirus.'' Li ...
'' (
''Bovine Coronavirus'', ''
Human coronavirus OC43
Human coronavirus OC43 (HCoV-OC43) is a member of the species '' Betacoronavirus 1'', which infects humans and cattle. The infecting coronavirus is an enveloped, positive-sense, single-stranded RNA virus that enters its host cell by binding to ...
''), ''
Hedgehog coronavirus 1
''Hedgehog coronavirus 1'' is a mammalian Group C '' Betacoronavirus'', a positive-sense RNA virus, discovered in European hedgehogs (''Erinaceus europaeus'') from Germany and first described in 2014.
Most ''Betacoronavirus'' clade c viruses are ...
,'' ''
Human coronavirus HKU1
''Human coronavirus HKU1'' (''HCoV-HKU1'') 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 first discovered in Jan ...
'', ''
Middle East respiratory syndrome-related coronavirus
''Middle East respiratory syndrome–related coronavirus'' (''MERS-CoV''), or EMC/2012 ( HCoV-EMC/2012), is the virus that causes Middle East respiratory syndrome (MERS). It is a species of coronavirus which infects humans, bats, and camels. Th ...
,'' ''
Murine coronavirus
Murine coronavirus (M-CoV) is a virus in the genus ''Betacoronavirus'' that infects mice. Belonging to the subgenus ''Embecovirus'', murine coronavirus strains are enterotropic or polytropic. Enterotropic strains include mouse hepatitis virus (M ...
'', ''
Pipistrellus bat coronavirus HKU5
''Pipistrellus bat coronavirus HKU5'' (''Bat-CoV HKU5'') is an enveloped, positive-sense single-stranded RNA mammalian Group 2 '' Betacoronavirus'' discovered in Japanese ''Pipistrellus'' in Hong Kong. This strain of coronavirus is closely relat ...
'', ''
Rousettus bat coronavirus HKU9
''Rousettus bat coronavirus HKU9'' (''HKU9-1'') is an enveloped, positive-sense, single-stranded RNA mammalian Group 2 ''Betacoronavirus'' discovered in ''Rousettus'' bats in China in 2011. This strain of coronavirus is closely related to the EM ...
'', ''
Severe acute respiratory syndrome–related coronavirus
''Severe acute respiratory syndrome–related coronavirus'' (SARSr-CoV or SARS-CoV)The terms ''SARSr-CoV'' and ''SARS-CoV'' are sometimes used interchangeably, especially prior to the discovery of SARS-CoV-2. This may cause confusion when some ...
'' (''
SARS-CoV
Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for ...
'', ''
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
''), ''
Tylonycteris bat coronavirus HKU4
''Tylonycteris bat coronavirus HKU4'' (''Bat-CoV HKU4'') is an enveloped, positive-sense single-stranded RNA virus mammalian Group 2 ''Betacoronavirus'' that has been found to be genetically related to the '' Middle East respiratory syndrome-rela ...
''
* Genus ''
Gammacoronavirus
''Gammacoronavirus'' (Gamma-CoV) is one of the four genera (''Alpha''-, '' Beta-'', ''Gamma-'', and '' Delta-'') of coronaviruses. It is in the subfamily ''Orthocoronavirinae'' of the family ''Coronaviridae''. They are enveloped, positive-sens ...
'';
** Species: ''
Avian coronavirus,'' ''
Beluga whale coronavirus SW1''
* Genus ''
Deltacoronavirus
''Deltacoronavirus'' (Delta-CoV) is one of the four genera ('' Alpha-'', '' Beta-'', '' Gamma-'', and ''Delta-'') of coronaviruses. It is in the subfamily ''Orthocoronavirinae'' of the family ''Coronaviridae''. They are enveloped, positive-se ...
''
** Species: ''
Bulbul coronavirus HKU11'',
''Porcine'' ''coronavirus HKU15''
Origin
![Animal origins of human coronaviruses](https://upload.wikimedia.org/wikipedia/commons/d/df/Animal_origins_of_human_coronaviruses.png)
The
most recent common ancestor
In biology and genetic genealogy, the most recent common ancestor (MRCA), also known as the last common ancestor (LCA) or concestor, of a set of organisms is the most recent individual from which all the organisms of the set are descended. The ...
(MRCA) of all coronaviruses is estimated to have existed as recently as 8000
BCE
Common Era (CE) and Before the Common Era (BCE) are year notations for the Gregorian calendar (and its predecessor, the Julian calendar), the world's most widely used calendar era. Common Era and Before the Common Era are alternatives to the or ...
, 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
Warm-blooded is an informal term referring to animal species which can maintain a body temperature higher than their environment. In particular, homeothermic species maintain a stable body temperature by regulating metabolic processes. The onl ...
flying vertebrates, are an ideal
natural reservoir
In infectious disease ecology and epidemiology, a natural reservoir, also known as a disease reservoir or a reservoir of infection, is the population of organisms or the specific environment in which an infectious pathogen naturally lives and r ...
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
The alpaca (''Lama pacos'') is a species of South American camelid mammal. It is similar to, and often confused with, the llama. However, alpacas are often noticeably smaller than llamas. The two animals are closely related and can success ...
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 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 family.Simmons, 20 ...
''; subsequently, they spread to horseshoe bats in the species ''
Rhinolophidae'', then to
Asian palm civet
The Asian palm civet (''Paradoxurus hermaphroditus''), also called common palm civet, toddy cat and musang, is a viverrid native to South and Southeast Asia. Since 2008, it is IUCN Red Listed as Least Concern as it accommodates to a broad rang ...
s, and finally to humans.
Unlike other betacoronaviruses,
bovine coronavirus
Bovine coronavirus (BCV or BCoV) is a coronavirus which is a member of the species ''Betacoronavirus 1''. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the N-acetyl-9- ...
of the species ''
Betacoronavirus 1
''Betacoronavirus 1'' is a species of coronavirus which infects humans and cattle. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus and is a member of the genus ''Betacoronavirus'' and subgenus ''Embecovirus.'' Li ...
'' and subgenus ''
Embecovirus
''Embecovirus'' is a subgenus of coronaviruses in the genus ''Betacoronavirus''. The viruses in this subgenus, unlike other coronaviruses, have a hemagglutinin esterase (HE) gene. The viruses in the subgenus were previously known as group 2a coro ...
'' is thought to have originated in
rodent
Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...
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
''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', ' ...
, 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
A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weak ...
.
In the 1950s, the human coronavirus OC43 began to diverge into its present
genotypes.
Phylogenetically, mouse hepatitis virus (''
Murine coronavirus
Murine coronavirus (M-CoV) is a virus in the genus ''Betacoronavirus'' that infects mice. Belonging to the subgenus ''Embecovirus'', murine coronavirus strains are enterotropic or polytropic. Enterotropic strains include mouse hepatitis virus (M ...
''), 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 and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
, 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
![Fphar-11-00937-g001](https://upload.wikimedia.org/wikipedia/commons/4/48/Fphar-11-00937-g001.jpg)
Coronaviruses vary significantly in risk factor. Some can kill more than 30% of those infected, such as
MERS-CoV
''Middle East respiratory syndrome–related coronavirus'' (''MERS-CoV''), or EMC/2012 ( HCoV-EMC/2012), is the virus that causes Middle East respiratory syndrome (MERS). It is a species of coronavirus which infects humans, bats, and camels. Th ...
, 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. Usually, causes of sore throat include
* viral infections
* group A streptococcal infection (GAS) bacterial infection
* pharyngitis (inflammation of the throat)
* to ...
from swollen
adenoid
In anatomy, the adenoid, also known as the pharyngeal tonsil or nasopharyngeal tonsil, is the superior-most of the tonsils. It is a mass of lymphatic tissue located behind the nasal cavity, in the roof of the nasopharynx, where the nose blends ...
s. Coronaviruses can cause
pneumonia
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...
(either direct
viral pneumonia
Viral pneumonia is a pneumonia caused by a virus. Pneumonia is an infection that causes inflammation in one or both of the lungs. The pulmonary alveoli fill with fluid or pus making it difficult to breathe. Pneumonia can be caused by bacteria, vir ...
or secondary
bacterial pneumonia
Bacterial pneumonia is a type of pneumonia caused by bacterial infection.
Types
Gram-positive
'' Streptococcus pneumoniae'' () is the most common bacterial cause of pneumonia in all age groups except newborn infants. ''Streptococcus 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
Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for ...
, which causes
severe acute respiratory syndrome
Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species, ''sev ...
(SARS), has a unique pathogenesis because it causes both
upper and
lower respiratory tract infection
Lower respiratory tract infection (LRTI) is a term often used as a synonym for pneumonia but can also be applied to other types of infection including lung abscess and acute bronchitis. Symptoms include shortness of breath, weakness, fever, cough ...
s.
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'', which infects humans and cattle. The infecting coronavirus is an enveloped, positive-sense, single-stranded RNA virus that enters its host cell by binding to ...
(HCoV-OC43),
β-CoV
#
Human coronavirus HKU1
''Human coronavirus HKU1'' (''HCoV-HKU1'') 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 first discovered in Jan ...
(HCoV-HKU1), β-CoV
#
Human coronavirus 229E
''Human coronavirus 229E'' (''HCoV-229E'') is a species of coronavirus which infects humans and bats. It is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the APN receptor. Along with Human c ...
(HCoV-229E),
α-CoV
#
Human coronavirus NL63
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, an ...
(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
''Middle East respiratory syndrome–related coronavirus'' (''MERS-CoV''), or EMC/2012 ( HCoV-EMC/2012), is the virus that causes Middle East respiratory syndrome (MERS). It is a species of coronavirus which infects humans, bats, and camels. Th ...
(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
Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species, ''seve ...
,
MERS
Middle East respiratory syndrome (MERS) is a viral respiratory infection caused by ''Middle East respiratory syndrome–related coronavirus'' (MERS-CoV). Symptoms may range from none, to mild, to severe. Typical symptoms include fever, cough, ...
, and
COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickly ...
respectively.
Common cold
Although the
common cold is usually caused by
rhinovirus
The rhinovirus (from the grc, ῥίς, rhis "nose", , romanized: "of the nose", and the la, vīrus) is the most common viral infectious agent in humans and is the predominant cause of the common cold. Rhinovirus infection proliferates in tem ...
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 climate
In geography, the temperate climates of Earth occur in the middle latitudes (23.5° to 66.5° N/S of Equator), which span between the tropics and the polar regions of Earth. These zones generally have wider temperature ranges throughout ...
s. 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 18 °C (64.4 °F) or higher in the cool ...
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 specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
(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
Human-to-human transmission (HHT) is an epidemiologic vector, especially in case the disease is borne by individuals known as superspreaders. In these cases, the basic reproduction number of the virus, which is the average number of additional pe ...
in France was confirmed by the French Ministry of Social Affairs and Health.
[''Nouveau coronavirus—Point de situation : Un nouveau cas d'infection confirmé''](_blank)
''(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
)
, image_map = Tunisia location (orthographic projection).svg
, map_caption = Location of Tunisia in northern Africa
, image_map2 =
, capital = Tunis
, largest_city = capital
, ...
. 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, constituting the southern part of the Korean Peninsula and sharing a land border with North Korea. Its western border is formed by the Yellow Sea, while its ea ...
, 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 population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of d ...
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 Province in the People's Republic of China. It is the largest city in Hubei and the most populous city in Central China, with a population of over eleven million, the ninth-most populous Chinese city an ...
, 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 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
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 nomenclatures for viruses. The ICTV has developed a universal taxonomic scheme for viruses, and thus has the means to ap ...
.
As of , there have been at least
confirmed deaths and more than
confirmed cases in the
COVID-19 pandemic
The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identi ...
. The Wuhan strain has been identified as a new strain of
Betacoronavirus
''Betacoronavirus'' (β-CoVs or Beta-CoVs) is one of four genera (''Alpha''-, ''Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. Member viruses are enveloped, positive-strand RNA viruses that infect mammals (of which humans are part). ...
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
Canine coronavirus (CCoV) is an enveloped, positive-sense, single-stranded RNA virus which is a member of the species ''Alphacoronavirus 1.'' It causes a highly contagious intestinal disease worldwide in dogs. The infecting virus enters its ho ...
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, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...
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
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
and are transmitted by a fecal-oral route. Significant research efforts have been focused on elucidating the
viral pathogenesis
Viral pathogenesis is the study of the process and mechanisms by which viruses cause diseases in their target hosts, often at the cellular or molecular level. It is a specialized field of study in virology.
Pathogenesis is a qualitative descripti ...
of these animal coronaviruses, especially by
virologist
Virology is the scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host cells for reproduction, thei ...
s interested in veterinary and
zoonotic
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
diseases.
Farm animals
Coronaviruses infect domesticated birds.
Infectious bronchitis virus
''Avian coronavirus'' is a species of virus from the genus '' Gammacoronavirus'' that infects birds; since 2018, all gammacoronaviruses which infect birds have been classified as this single species. The strain of avian coronavirus previously kn ...
(IBV), a type of coronavirus, causes
avian infectious bronchitis.
The virus is of concern to the
poultry industry
Poultry farming is the form of animal husbandry which raises domesticated birds such as chickens, ducks, turkeys and geese to produce meat or eggs for food. Poultry – mostly chickens – are farmed in great numbers. More than 60 billion ch ...
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 preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. 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
Enteritis is inflammation of the small intestine. It is most commonly caused by food or drink contaminated with pathogenic microbes,Dugdale, David C., IIII, and George F Longretc"Enteritis" MedlinePlus Medical Encyclopedia, 18 October 2008. Access ...
in
turkeys
The turkey is a large bird in the genus ''Meleagris'', native to North America. There are two extant turkey species: the wild turkey (''Meleagris gallopavo'') of eastern and central North America and the ocellated turkey (''Meleagris ocellat ...
.
Coronaviruses also affect other branches of
animal husbandry such as
pig farming
Pig farming or pork farming 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) and skins.
Pigs are amenable t ...
and the Cattle raising.
Swine acute diarrhea syndrome coronavirus (SADS-CoV), which is related to
bat coronavirus HKU2, causes
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
in pigs.
Porcine epidemic diarrhea virus
''Porcine epidemic diarrhea virus'' (PED virus or PEDV) is a coronavirus that infects the cells lining the small intestine of a pig, causing porcine epidemic diarrhoea, a condition of severe diarrhea and dehydration. Older hogs mostly get sick ...
(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
Bovine coronavirus (BCV or BCoV) is a coronavirus which is a member of the species ''Betacoronavirus 1''. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the N-acetyl-9- ...
(BCV), which is a member of the species ''
Betacoronavirus 1
''Betacoronavirus 1'' is a species of coronavirus which infects humans and cattle. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus and is a member of the genus ''Betacoronavirus'' and subgenus ''Embecovirus.'' Li ...
'' 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
Feline coronavirus (FCoV) is a positive-stranded RNA virus that infects cats worldwide. It is a coronavirus of the species '' Alphacoronavirus 1'' which includes canine coronavirus (CCoV) and porcine transmissible gastroenteritis coronavirus (T ...
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 replication, DNA or viral repl ...
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
Canine coronavirus (CCoV) is an enveloped, positive-sense, single-stranded RNA virus which is a member of the species ''Alphacoronavirus 1.'' It causes a highly contagious intestinal disease worldwide in dogs. The infecting virus enters its ho ...
(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
''Betacoronavirus 1'' is a species of coronavirus which infects humans and cattle. The infecting virus is an enveloped, positive-sense, single-stranded RNA virus and is a member of the genus ''Betacoronavirus'' and subgenus ''Embecovirus.'' Li ...
'' 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
Murine coronavirus (M-CoV) is a virus in the genus ''Betacoronavirus'' that infects mice. Belonging to the subgenus ''Embecovirus'', murine coronavirus strains are enterotropic or polytropic. Enterotropic strains include mouse hepatitis virus (M ...
'',
causes an epidemic
murine
The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families ex ...
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
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'' and ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' 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.
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
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
References
Further reading
*
*
*
*
*
{{Portal bar, COVID-19, Medicine, Viruses
Animal virology
Virus subfamilies