Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility

Abstract

Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S 2 domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S D domain) and G1124V (in S 2 subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird's eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India.

Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: An endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations

“…RNA viruses display a characteristic feature of high mutability and with no exception, SARS-CoV-2 being a positive strand RNA virus has been evolving at a rapid rate since its emergence in Wuhan during the end of 2019. In the span of six months (December, 2019-June, 2020), the circulating SARS-CoV-2 strains have accumulated a large number of mutations which might result in altered virulence, infectivity and transmissibility [3,4].…”

PAN-INDIA 1000 SARS-CoV-2 RNA Genome Sequencing Reveals Important Insights into the Outbreak

“…An interesting set of mutations which has enriched during the course of the outbreak in India has been the emergence of the RG203KR in the N gene. Since its detection in few sequences obtained from individuals in April 2020 (15), this mutation has been found to gain abundance, especially in the West, South and North region but not in the East in our sequence data. Further analysis and studies are required to be undertaken to understand the implication of this observation, since this mutation is expected to alter potential miRNA binding sites and cause changes in the structure of the nucleocapsid.…”

“…Since the initial sequence data from the first reported cases, there have been attempts by various medical and scientific research organisations to generate whole-genome sequence data from infected cases in India (12)(13)(14)(15). Understanding the necessity of generation of large scale viral wholegenome sequences representing geographic locations all over the country and at different time points of the outbreak, a PAN-INDIA 1000 SARS-CoV-2 RNA Genome Sequencing Consortium of scientific research organisations and their collaborating clinical partners was formed under the aegis of Department of Biotechnology, Ministry of Science and Technology, Government of India (Figure 1).…”

Identification of novel mutations in SARS-COV-2 isolates from Turkey

“…At NSP12/RdRP gene, alanine/valine substitution was observed at site 4489 in a single sequence (EPI_ISL_455719, Turkey / Mardin) on April 9th, 2020 which was not found in any other sequence in this report. In a previous report by Maitra et al [34], this unique mutation was also depicted in two infected individuals of India.…”