About Coronavirus
Corona viruses are a group of related Viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold (which has other possible causes, predominantly rhinoviruses),
while more lethal varieties can cause SARS, MERS, and COVID-19. Symptoms in other species vary: in chickens, they cause an upper respiratory tract diseases, while in cows and pigs they cause diarrhea. There are yet to be vaccines or antiviral drugs to prevent or treat human coronavirus.
Genome
According to the 29,751-base genome of the severe acute respiratory syndrome (SARS)–associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus
infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.
An outbreak of atypical pneumonia, referred to as severe acute respiratory syndrome (SARS) and first identified in Guangdong Province, China, has spread to several countries. The severity of this disease is such that the mortality rate appears to be ∼3 to 6%, although a recent report suggests this rate can be as high as 43 to 55% in people older than 60 years.
The National Microbiology Laboratory in Canada obtained the Tor2 isolate from a patient in Toronto and succeeded in growing a coronavirus-like agent in African green monkey kidney (Vero E6) cells. This coronavirus was named publicly by the World Health Organization and member laboratories as the “SARS virus” (WHO press release, 16 April 2003) after tests of causation according to Koch's postulates, including monkey inoculation .
Structure
The coronaviruses are members of a family of enveloped viruses that replicate in the cytoplasm of animal host cells.They are distinguished by the presence of a single-stranded plus-sense RNA genome about 30 kb in length that has a 5′ cap structure and 3′ polyadenylation tract. Upon infection of an appropriate host cell, the 5′-most open reading frame (ORF) of the viral genome is translated into a large polyprotein that is cleaved by viral-encoded proteases to release several nonstructural proteins, including an RNA-dependent RNA polymerase (Rep) and an adenosine triphosphatase (ATPase) helicase (Hel). These proteins, in turn, are responsible for replicating the viral genome as well as generating nested transcripts that are used in the synthesis of the viral proteins. The mechanism by which these subgenomic mRNAs are made is not fully understood.
The viral membrane proteins, including the major proteins S (Spike) and M (membrane), are inserted into the endoplasmic reticulum (ER) Golgi intermediate compartment while full-length replicated RNA plus strands assemble with the N (nucleocapsid) protein. This RNA-protein complex then associates with the M protein embedded in the membranes of the ER, and virus particles form as the nucleocapsid complex buds into the lumen of the ER. The virus then migrates through the Golgi complex and eventually exits the cell, likely by exocytosis.
The site of viral attachment to the host cell resides within the S protein.
The coronaviruses include a large number of viruses that infect different animal species. The predominant diseases associated with these viruses are respiratory and enteric infections, although hepatic and neurological diseases also occur.
Purification of viral particles and RNA, and DNA sequencing. Virus isolation was performed on a bronchoalveolar lavage specimen of a fatal SARS case belonging to the original case cluster from Toronto, Canada. Viral particles from this Tor2 isolate were purified, and the genetic material (RNA) was extracted from the Tor2 isolate.The RNA was converted to cDNA by means of a combined random-priming and oligo(dT) priming strategy.
Predicted protein coding features of the Tor2 SARS-CoV genome sequence.
ORFs were determined initially through sequence similarity to known coronavirus proteins. This approach identified replicases 1a and 1b, the S protein, the small envelope (E) protein, the M protein, and the N protein. ORFs that did not match database sequences were identified if they were larger than 40 amino acids, unless a strong match to the TRS consensus was found close to and upstream of the potential initiating methionine residue.
Reproduction of Corona Viruses
An animal virus for which the normal host is currently unknown recently mutated and developed the ability to productively infect humans. There also remains the possibility that the SARS virus evolved from a previously harmless human coronavirus. However, preliminary evidence suggests that antibodies to this virus are absent in people not infected with SARS-CoV.
The availability of the SARS virus genome sequence is important from a public health perspective. It will allow the rapid development of PCR-based assays for this virus that capitalize on novel sequence features, enabling discrimination between this and other circulating coronaviruses. Such assays will allow the diagnosis of SARS virus infection in humans and, critically, will consolidate the association of this virus with SARS. If the association is further borne out, SARS virus genome–based PCR assays may form an important part of a public health strategy to control the spread of this syndrome. In the longer term, this information will assist in the development of antiviral treatments, including neutralizing antibodies and development of a vaccine to treat this emerging and deadly disease.
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