Decoding the Terror Code: Genome Sequencing of SARS-CoV- Strains from Mumbai
The novel coronavirus (COVID-19) has infected over 92 million people globally and over 10.5 million people in India, and has led to death of almost 2 million people globally and over 0.15 million in India since Dec 2019. To get insights into this virus, laboratories from various countries affected with COVID-19 started sequencing genomes of SARS-CoV-2 strains obtained from infected patients and collected related clinical and epidemiological data associated with the newly emerging coronavirus, which is rapidly made available via the Global Initiative on Sharing All Influenza Data (GISAID)
The genome sequences of SARS-CoV-2 strains are important for designing/evaluating diagnostic tests, for tracking/tracing the ongoing COVID-19 outbreak and for identifying potential intervention options. It has been over a year since the first novel SARS-CoV-2 genome sequence was made publicly available and since then, it has resulted in unmatched growth in field of genomics, vaccine and diagnostic testing across the field of infection biology the world has ever seen. Currently, the GISAID database has over 350,000 SARS-CoV-2 genomes freely available to anyone interested in conducting genomic analysis. Whole genome sequencing within a matter of hours to days to determine the genomic characteristics of the virus has provided beneficial insights to what humans can do at the uncertain times of pandemic.
Unfortunately, there is currently a dearth of information on the viral strain types in India in the global database (with only over 4,300 strains from India, <0.05% cases sequenced), leading to lack of understanding and control over the viral strains in the country. In contrast, a country like UK
has sequenced over 5% of its cases (https://science.thewire.in/the-sciences/india-sars-cov-2-genome-sequencing-roadblocks-resources-b117-n440k-variants).
At the Foundation for Medical Research (FMR) we isolated the viral genomic RNA from 5 strains of SARS-CoV-2 collected from 5 COVID-19 patients between Aug-Sep 2020 (4 from nasopharyngeal swabs and 1 from membrane-lined N-95 mask) from Kasturba hospital. The sequence data obtained was analyzed to determine and understand the genomic structure and to find mutations (changes in the genome) in the 5 SARS-CoV-2 strains in comparison to the original Wuhan strain (Dec 2019) over time.
Mutations/changes (ranging from 8 to 22 mutations per genome) were observed in the genome of the 5 viral strains. All 5 SARS-CoV-2 strains were found to have the (D614G) mutation/change in the spike protein — a protein that is present on the surface of the virus and is required for the attachment of the virus to the host cell. This mutation/change leads to increased affinity of the virus to bind to the surface of the host cell and results in increase in efficiency of the virus to enter the host cell. Efficient entry of the virus into the host cells lead to increase in the intracellular viral load in patients having a viral strain with this genomic mutation/change. This predominant mutation/change has evolved in the viral strains since mid-Feb 2020 and is now found in almost all the SARS-CoV-2 strains globally. Another genomic mutation/change (c14408t in ORF1ab gene) was found in all 5 strains. This mutation/change is in the protein that produces new viral RNA in the host cell (it is part of the RNA dependent RNA polymerase) and has the potential to increase the rate of evolution of the virus leading to development of more virulent/infectious viral strains in future. All the strains belonged to the parent lineage B which is the pre-dominant lineage in the Indian population. The genome sequences of all the 5 strains have been uploaded on the GISAID database and are freely available for research use.
With the continuous evolution of the SARS-CoV-2 strains and concerns over the UK and South African variant strains that are notorious for their high transmission rates (70% more contagious) and increased immune evasion, respectively, it has become even more important to sequence as many viral strains as possible. In light of the new variant strains of SARS-CoV-2, prospective surveillance based on whole genome sequencing of 5% of the positive cases is being conducted by the National Task Force (NTF) in India through the Indian SARS-CoV-2 Genomics Consortium (INSACOG) labs — a group of 10 government labs. Considering the urgent sequencing need, FMR has also extended its support to the NTF for prospective surveillance by conducting genome sequencing of the SARS-CoV-2 strains from Mumbai (and Maharashtra) using Nanopore sequencing.
In near future, FMR plans to undertake additional studies on the genomics of SARS-CoV 2 not only for strain detection and surveillance but also to understand its activity through the integrity of the genome. This will allow us to understand what a positive RT-PCR test really means.
Dear Reader,
We are looking for financial support to undertake the study areas outline. If you wish to seek further details and contribute, please get in touch with us at fmr@fmrindia.org.
Thank you.
