Coronaviruses are a group of related viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that can be mild, such as some cases of the common cold (among other possible causes, predominantly rhinoviruses), and others that can be lethal, such as SARS, MERS, and COVID-19. Symptoms in other species vary: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea. There are yet to be vaccines or antiviral drugs to prevent or treat human coronavirus infections.
Coronaviruses constitute the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales, and realm Riboviria.[ They have enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 27 to 34 kilobases, the largest among known RNA viruses. The name coronavirus is derived from the Latin corona, meaning “crown” or “halo”, which refers to the characteristic appearance reminiscent of a crown or a solar corona around the virions (virus particles) when viewed under two-dimensional transmission electron microscopy, due to the surface covering in club-shaped protein spikes
Coronaviruses were first discovered in the late 1960s] The earliest ones discovered were an infectious bronchitis virus in chickens and two in human patients with the common cold (later named human coronavirus 229E and human coronavirus OC43Other members of this family have since been identified, including SARS-CoV in 2003, HCV NL63 in 2004, HKU1 in 2005, MERS-CoV in 2012, and SARS-CoV-2 (formerly known as 2019-nCoV) in 2019. Most of these have involved serious respiratory tract infections.
The name “coronavirus” is derived from Latin corona, meaning “crown” or “wreath”, itself a borrowing from Greek κορώνη korṓnē, “garland, wreath”. The name refers to the characteristic appearance of virions (the infective form of the virus) by electron microscopy, which has a fringe of large, bulbous surface projections creating an image reminiscent of a crown or of a solar corona. This morphology is created by the viral spike peplomers, which are proteins on the surface of the virus.
Coronaviruses are large pleomorphic spherical particles with bulbous surface projections The diameter of the virus particles is around 120 nm.[The envelope of the virus in electron micrographs appears as a distinct pair of electron-dense shells
The viral envelope consists of a lipid bilayer where the membrane (M), envelope (E) and spike (S) structural proteins are anchored] A subset of coronaviruses (specifically the members of Betacoronavirus subgroup A) also have a shorter spike-like surface protein called hemagglutinin esterase (HE)]
Inside the envelope, there is the nucleocapsid, which is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-stranded RNA genome in a continuous beads-on-a-string type conformation] The genome size for coronaviruses ranges from approximately 27 to 34 kilobases] The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell.
Infection begins when the virus enters the host organism and the 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 allow cell entry through endocytosis or direct fusion of the viral envelop with the host membrane.
On entry into the host cell, the virus particle is uncoated, and its genome enters the cell cytoplasm] The coronavirus RNA genome has a 5′ methylated cap and a 3′ polyadenylated tail, which allows the RNA to attach to the host cell’s ribosome for translation. The host ribosome translates the initial overlapping open reading frame of the virus genome and forms a long polyprotein. The polyprotein has its own proteases that cleave the polyprotein into multiple nonstructural proteins.
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 non-structural protein, for instance, provides extra fidelity to replication by providing a proofreading function which the RNA-dependent RNA polymerase lacks.
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] 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 is followed by the transcription of these negative-sense subgenomic RNA molecules to their corresponding positive-sense
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 a number of 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 M proteins direct most protein-protein interactions required for the mbly of viruses following its binding to the nucleocapsid. Progeny viruses are then released from the host cell by exocytosis through secretory vesicles.
Human to human transmission of coronaviruses is primarily thought to occur among close contacts via respiratory droplets generated by sneezing and coughing. The interaction of the coronavirus spike protein with its complement host cell receptor is central in determining the tissue tropism, infectivity, and species range of the virus] The SARS coronavirus, for example, infects human cells by attaching to the angiotensin-converting enzyme 2 (ACE2) receptor.
The most recent common ancestor (MRCA) of all coronaviruses has been placed at around 8000 BCE. he MRCAs of the Alphacoronavirus line has been placed at about 2400 BCE, the Betacoronavirus line at 3300 BCE, the Gammacoronavirus line at 2800 BCE, and the Deltacoronavirus line at about 3000 BCE. It appears that bats and birds, as warm-blooded flying vertebrates, are ideal hosts for the coronavirus gene source (with bats for Alphacoronavirus and Betacoronavirus, and birds for Gammacoronavirus and Deltacoronavirus) to fuel coronavirus evolution and dissemination.
Bovine coronavirus and canine respiratory coronaviruses diverged from a common ancestor in 1951]Bovine coronavirus and human coronavirus OC43 diverged around the 1890s. Bovine coronavirus diverged from the equine coronavirus species at the end of the 18th century.
The MRCA of human coronavirus OC43 has been dated to the 1950s.
MERS-CoV, although related to several bat coronavirus species, appears to have diverged from these several centuries ago] The human coronavirus NL63 and a bat coronavirus shared an MRCA 563–822 years ago.
The most closely related bat coronavirus and SARS-CoV diverged in 1986.] A path of evolution of the SARS virus and an en relationship with bats have been proposed. The authors suggest that the coronaviruses have been coevolved with bats for a long time and the ancestors of SARS-CoV first infected the species of the genus Hipposideridae, subsequently spread to species of the Rhinolophidae and then to civets, and finally to humans.
Alpaca coronavirus and human coronavirus 229E diverged before 1960.
Coronaviruses vary significantly in the risk factors. Some can kill more than 30% of those infected (such as MERS-CoV), and some are relatively harmless, such as the common cold. Coronaviruses cause colds with major symptoms, such as fever, and a sore throat from swollen adenoids, occurring primarily in the winter and early spring seasons. Coronaviruses can cause pneumonia (either direct viral pneumonia or secondary bacterial pneumonia) and bronchitis (either direct viral bronchitis or secondary bacterial bronchitis). The much-publicized human coronavirus discovered in 2003, SARS-CoV, which causes severe acute respiratory syndrome (SARS), has unique pathogenesis because it causes both upper and lower respiratory tract infections
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 (WHO) issued a press release stating that a novel coronavirus identified by a number of laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV). More than 8,000 people were infected, about ten percent of whom died.
The 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). he 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. n addition, cases of human-to-human transmission were reported by the Ministry of Health in Tunisia. Two confirmed cases involved people who seemed to have caught the disease from their late father, who became ill after a visit to Qatar and Saudi Arabia. Despite this, it appears the virus had trouble spreading from human to human, as most individuals who are infected do not transmit the virus 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 (HCV-EMC). The final name for the virus is Middle East respiratory syndrome coronavirus (MERS-CoV). In May 2014, the only two United States cases of MERS-CoV infection were recorded, both occurring in healthcare workers who worked in Saudi Arabia and then traveled to the U.S. One was treated in Indiana and one in Florida. Both were hospitalized temporarily and then discharged. n May 2015, an outbreak of MERS-CoV occurred in the Republic of Korea, when a man who had traveled to the Middle East, visited 4 hospitals in the Seoul area to treat his illness. This caused one of the largest outbreaks of MERS-CoV outside the Middle Eas As of December 2019, 2,468 cases of MERS-CoV infection had been confirmed by laboratory tests, 851 of which were fatal, a mortality rate of approximately 34.5%Coronavirus disease 2019 (COVID-19)
In December 2019, a pneumonia outbreak was reported in Wuhan, China. On 31 December 2019, the outbreak was traced to a novel strain of coronavirus, which was given the interim name 2019-to by the World Health Organization (WHO) later renamed SARS-CoV-2 by the International Committee on Taxonomy of Viruses. Some researchers have suggested that the Huanan Seafood Wholesale Market may not be the original source of viral transmission to humans.
As of 17 March 2020, there have been at least 7,154 confirmed deaths and more than 182,405irmed cases in the coronavirus pneumonia pandemic. The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with approximately 70% genetic similarity to the SARS-CoV. The virus has a 96% similarity to a bat coronavirus, so it is widely suspected to originate from bats as well. The pandemic has resulted in serious travel restrictions.
Coronaviruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. They also cause a range of diseases in farm animals and domesticated pets, some of which can be serious and are a threat to the farming industry. In chickens, the infectious bronchitis virus (IBV), a coronavirus, targets not only the respiratory tract but also the urogenital tract. The virus can spread to different organs throughout the chicken. economically significant coronaviruses of farm animals include porcine coronavirus (transmissible gastroenteritis coronavirus, TGE) and bovine coronavirus, which both result in diarrhea in young animals. Feline coronavirus: two forms, feline enteric coronavirus is a pathogen of minor clinical significance, but spontaneous mutation of this virus can result in feline infectious peritonitis (FIP), a disease associated with high mortality. 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). There are two types of canine coronavirus (CCTV), one that causes mild gastrointestinal disease and one that has been found to cause respiratory disease. Mouse hepatitis virus (MHV) is a coronavirus that causes an epidemic murine illness with high mortality, especially among colonies of laboratory mice Sialodacryoadenitis virus (SDAV) is a highly infectious coronavirus of laboratory rats, which can be transmitted between individuals by direct contact and indirectly by aerosol. Acute infections have high morbidity and tropism for the salivary, lachrymal and harderian glands.
An HKU2-related bat coronavirus called swine acute diarrhea syndrome coronavirus (SADS-CoV) causes diarrhea in pigs.
Prior to the discovery of SARS-CoV, MHV had been the best-studied coronavirus both in vivo and in vitro as well as at the molecular level. Some strains of MHV cause progressive demyelinating encephalitis in mice which has been used as a murine model for multiple sclerosis. Significant research efforts have been focused on elucidating the viral pathogenesis of these animal coronaviruses, especially by virologists interested in veterinary and zoonotic diseases.
In domestic animals
- Infectious bronchitis virus (IBV) causes avian infectious bronchitis.
- Porcine coronavirus (transmissible gastroenteritis coronavirus of pigs, TGEV).
- Bovine coronavirus (BCV), responsible for severe profuse enteritis in young calves.
- Feline coronavirus (FCoV) causes mild enteritis in cats as well as severe Feline infectious peritonitis (other variants of the same virus).
- the two types of canine coronavirus (CCTV) (one causing enteritis, the other found in respiratory diseases).
- Turkey coronavirus (TCV) causes enteritis in turkeys.
- Ferret enteric coronavirus causes epizootic catarrhal enteritis in ferrets.
- Ferret systemic coronavirus causes FIP-like systemic syndrome in ferrets.
- Pantropic canine coronavirus.
- Rabbit enteric coronavirus causes acute gastrointestinal disease and diarrhea in young European rabbits. Mortality rates are high.
- Porcine epidemic diarrhea virus (PED or PEDV), has emerged around the world.
Genomic cis-acting elements
In common with the genomes of all other RNA viruses, coronavirus genomes contain cis-acting RNA elements that ensure the specific replication of viral RNA by a virally encoded RNA-dependent RNA polymerase. The embedded cis-acting elements devoted to coronavirus replication constitute a small fraction of the total genome, but this is presumed to be a reflection of the fact that coronaviruses have the largest genomes of all RNA viruses. The boundaries of cis-acting elements essential to replication are fairly well-defined, and the RNA secondary structures of these regions are understood. However, how these cis-acting structures and sequences interact with the viral replicase and host cell components to allow RNA synthesis is not well understood
The assembly of infectious coronavirus particles requires the selection of viral genomic RNA from a cellular pool that contains an abundant excess of non-viral and viral RNAs. Among the seven to ten specific viral mRNAs synthesized in virus-infected cells, only the full-length genomic RNA is packaged efficiently into coronavirus particles. Studies have revealed cis-acting elements and trans-acting viral factors involved in the coronavirus genome encapsidation and packaging. Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies and viral expression vectors based on the coronavirus genome.