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April 16, 2020 – Report on the Ongoing SARS-CoV-2 Pandemic causing the COVID-19 Disease

Reporter and Curator: Mr. Srinjoy Chakraborty (Junior Research Fellow) and Dr. Sudipta Saha, Ph.D.

 

Introduction:

In December 2019, several cases of viral pneumonia of unknown origin were reported in the city of Wuhan, China. Further investigation by the national regulatory authorities revealed that many of the registered cases had links to the Huanan wholesale seafood market. A novel corona virus was identified after broncho-alveolar lavage fluid from patients with pneumonia of unknown origin was inoculated in human airway epithelial cells and Vero E6 and Huh7 cell lines. A few days later, the whole genome sequence of this novel virus was published, and it was named as the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses because of its close resemblance to the SARS-CoV, which had infected approximately 8000 individuals worldwide.

The first SARS-CoV-2­-related death was reported on the 11^th of January, 2020. Today, having spread to approximately 213 countries and territories and claiming a total of 1,30,885 lives worldwide (as of 16^th April 2020), the SARS-CoV-2 pandemic has left several leading economies in ruins.

 

Genome and Phylogenetics:

The novel SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus that belongs to the broad family of viruses known as coronaviridae. The viruses belonging to this family are further divided into four genera: Alpha-, Beta-, Gamma-, and Delta-coronavirus. Other viruses belonging to this family are known to cause illnesses ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS).

The SARS-Cov-2 is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV and the original SARS-CoV. With a diameter of approximately 65–125 nm, the genome of the coronavirus is approximately 30 kb-long. The four important structural components of the virus are the envelope protein (E) membrane protein (M) spike protein (S) and nucleocapsid protein (N).

Phylogenetic analysis of SARS-CoV-2 that were isolated from patients in Wuhan revealed that it was closely related to a SARS-like (SL) CoV, RaTG13, which was obtained from infected Rhinolophus sinicus in a cave in Yunnan, China, in 2013. These two viruses share approximately 96% of nucleotide sequence identities, thus confirming it to be of zoonotic origin

 

Biochemistry and mechanism of infection:

Biochemical and structural studies have revealed that the SARS-CoV-2 utilizes a densely glycosylated spike (S) protein to enter host cells. The two functional domains of the S protein are a receptor binding domain and a domain that mediates fusion of the viral and cell membranes. A furin like cleavage site in the S protein results in the cleavage of the protein, thus mediating fusion of the viral and cell membranes.

The receptor binding domain (RBD) of the S protein binds to angiotensin-converting enzyme 2 (ACE2) in host cells with higher affinity compared to severe acute respiratory syndrome (SARS)-CoV. ACE2 is a membrane-associated aminopeptidase that is expressed in vascular endothelia, renal and cardiovascular tissue, and epithelia of the small intestine and testes. Several studies have demonstrated that overexpression of ACE2 enhanced the severity of the disease in mouse, human and other animal models. It has been reported that the epithelial cells that line the respiratory tract, especially the lung epithelia and the alveolar epithelial type 2 cells, are more susceptible to infection by the virus and that these cells act as reservoirs for viral invasion. These viruses cause acute lung injury and acute respiratory disease syndrome.

India and SARS-CoV-2:

With a steady increase in the number of patients who are testing positive for SARS-CoV-19, national and international regulatory bodies are taking crucial and radical steps to curb and reduce the number of cases. On the 14th of April, the Indian government extended the ongoing lockdown till the 3rd of May, 2020. Social distancing has been the most effective way of avoiding the spread of this disease. Various organisations in the private and public sectors are engaged in developing diagnostic kits and possible therapies for tackling this pandemic.

Based on the reports and protocols in China, the Indian Council of Medical Research (ICMR) started screening passengers arriving from China and other countries from the 18th of January. Several citizens who were evacuated from the pandemic hit areas across the globe were screened upon their arrival to the country. Samples were first sent to the National Institute of Virology for screening. After genome sequence of the SARS-CoV-2 virus was published in China, candidate diagnostic real-time reverse transcription-polymerase chain reaction (rRTPCR) assays were designed and made available in the public domain for researchers. This method targeted the SARS-CoV-2-specific E gene. Confirmatory assays targeted the ‘RdRp gene’, ‘N gene’ and ‘ORF-1b’. An optimized method of the same assay was developed by the ICMR-National Institute of Virology to detect various genomic regions of the SARS-Cov-2. Recently, the ICMR also approved a diagnostic kit for detecting antibodies in blood samples. This kit detects IgM and IgG antibodies in blood samples. This method is not only a cheaper alternative but also a rapid test. However, as of 13th April, 2020, this testing is yet to begin in India as the country is currently awaits the import of rapid test kits. Housing the country’s only biosafety level 4 laboratory, scientists at the NIV recently published an electron micrograph image of the SARS-CoV-2 viral particle.

Although much is known about the physiology and the mode of action of SARS-CoV-2, we are still far away from developing a vaccine or a treatment. Several promising vaccine candidates against SARS-Cov-2 include live viruses, recombinant protein subunits, and nucleic acids. Several pharmaceutical organizations and universities are now attempting to fast track ways of developing a vaccine as soon as possible.

Social distancing and mass awareness continue to be the most effective way in tackling the spread of this disease. We must also consider the fact that COViD-19 is the 3rd pandemic caused by a virus belonging to the coronavirus family in the last 20 years; SARS in 2002, MERS in 2012, and now COVID-19. Therefore stockpiling and developing vaccines, testing kits, personal protective equipment, as well as identifying international funding mechanisms to support the development, manufacture, and storage of vaccines and therapeutic alternatives is of utmost priority today.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/32259829

 

https://www.ncbi.nlm.nih.gov/pubmed/32257431

 

https://www.ncbi.nlm.nih.gov/pubmed/32166607

 

https://www.ncbi.nlm.nih.gov/pubmed/32259480

 

http://www.who.int/emergencies/diseases/novel-coronavirus-2019

 

https://www.ncbi.nlm.nih.gov/pubmed/32075877

 

https://www.ncbi.nlm.nih.gov/pubmed/32284615

 

https://www.ncbi.nlm.nih.gov/pubmed/32278175

 

https://www.ncbi.nlm.nih.gov/pubmed/32125455

 

https://www.ncbi.nlm.nih.gov/pubmed/32242875

 

http://www.theweek.in/news/india/2020/03/25/niv-studies-covid-19-virus-long-way-from-vaccine-development.html

 

https://www.ncbi.nlm.nih.gov/pubmed/32219057