Covid 19
Discovery
Human 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 OC43).Other members of this family have since been identified, including SARS-CoV in 2003, HCoV 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.Etymology
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 have 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.Morphology
Cross-sectional model of a coronavirus
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 lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell.
Genome
Schematic representation of the genome organization and functional domains of S protein for SARS-CoV and MERS-CoV.
The genome organization for a coronavirus is 5′-leader-UTR-replicase/transcriptase-spike (S)-envelope (E)-membrane (M)-nucleocapsid (N)-3′UTR-poly (A) tail. The open reading frames 1a and 1b, which occupy the first two-thirds of the genome, encode the replicase/transcriptase polyprotein. The replicase/transcriptase polyprotein self cleaves to form the nonstructural proteins (nsps).
The later reading frames encode the four major structural proteins: spike, envelope, membrane, and nucleocapsid.Interspersed between these reading frames are the reading frames for the accessory proteins. The number of accessory proteins and their function is unique depending on the specific coronavirus.
Life cycle
Entry
The life cycle of a coronavirus
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 which cleave the polyprotein into multiple nonstructural proteins.
Replication
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 mRNAs.
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 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 assembly of viruses following its binding to the nucleocapsid.Progeny viruses are then released from the host cell by exocytosis through secretory vesicles.Transmission
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.Taxonomy
Phylogenetic tree of coronaviruses
- Genus: Alphacoronavirus
- Genus Betacoronavirus; type species: Murine coronavirus
- Species: Betacoronavirus 1, Human coronavirus HKU1, Murine coronavirus, Pipistrellus bat coronavirus HKU5, Rousettus bat coronavirus HKU9, Severe acute respiratory syndrome-related coronavirus, Severe acute respiratory syndrome coronavirus 2, Tylonycteris bat coronavirus HKU4, Middle East respiratory syndrome-related coronavirus, Human coronavirus OC43, Hedgehog coronavirus 1 (EriCoV)
- Genus Gammacoronavirus; type species: Infectious bronchitis virus
- Genus Deltacoronavirus; type species: Bulbul coronavirus HKU11
Evolution
The most recent common ancestor (MRCA) of all coronaviruses has been estimated to have existed as recently as 8000 BCE, though some models place the MRCA as far back as 55 million years or more, implying long term coevolution with bats.The 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 recently (~ 1950).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 keen 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.
Illustration of SARSr-CoV virion
Seven strains of human coronaviruses are known, of which four produce the generally mild symptoms of the common cold:
- Human coronavirus OC43 (HCoV-OC43)
- Human coronavirus HKU1
- Human coronavirus NL63 (HCoV-NL63, New Haven coronavirus)
- Human coronavirus 229E (HCoV-229E)
- Middle East respiratory syndrome-related coronavirus (MERS-CoV), previously known as novel coronavirus 2012 and HCoV-EMC
- Severe acute respiratory syndrome coronavirus (SARS-CoV or "SARS-classic")
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019-nCoV or "novel coronavirus 2019"
Outbreaks of coronavirus types of relatively high mortality are as follows:
| Outbreak | Virus type | Deaths |
|---|---|---|
| 2003 severe acute respiratory syndrome outbreak | SARS-CoV | 774 |
| 2012 Middle East respiratory syndrome coronavirus outbreak | MERS-CoV | Over 400 |
| 2015 Middle East respiratory syndrome outbreak in South Korea | MERS-CoV | 36 |
| 2018 Middle East respiratory syndrome outbreak | MERS-CoV | 41 |
| 2019–2020 coronavirus pandemic | SARS-CoV-2 | At least 17,159 |
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.
Middle East respiratory syndrome (MERS)
In September 2012, a new type of coronavirus was identified, initially called Novel Coronavirus 2012, and now officially named Middle East respiratory syndrome coronavirus (MERS-CoV).The World Health Organization issued a global alert soon after. The WHO update on 28 September 2012 said the virus did not seem to pass easily from person to person.However, on 12 May 2013, a case of human-to-human transmission in France was confirmed by the French Ministry of Social Affairs and Health. In addition, cases of human-to-human transmission were reported by the Ministry of Health in Tunisia. Two confirmed cases involved people who seemed to have caught the disease from their late father, who became ill after a visit to Qatar and Saudi Arabia. Despite this, it appears the virus had trouble spreading from human to human, as most individuals who are infected do not transmit the virus. 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). 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 travelled to the U.S. One was treated in Indiana and one in Florida. Both were hospitalized temporarily and then discharged.
In May 2015, an outbreak of MERS-CoV occurred in the Republic of Korea, when a man who had traveled to the Middle East, visited 4 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 of approximately 34.5%.
As of 24 March 2020, there have been at least 17,159 confirmed deaths and more than 392,780 confirmed 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 travel restrictions and nationwide lockdowns in several countries.
Other animals
Coronaviruses have been recognized as causing pathological conditions in veterinary medicine since the early 1970s. Except for avian infectious bronchitis, the major related diseases have mainly an intestinal location.Diseases caused
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.[70] 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 (CCoV), 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 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.A 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 a 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 of 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 (CCoV) (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.
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