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

Abstract

Accumulation of mutations within the genome is the primary driving force for viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility as well as antigenic shift to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we aimed at genome-wide analyses of circulating SARS-CoV-2 viruses for the emergence of novel co-existing mutations and trace their spatial distribution within India. Comprehensive analysis of whole genome sequences of 441 Indian SARS-CoV-2 strains revealed the occurrence of 33 different mutations, 21 being distinctive to India. Emergence of novel mutations were observed in S glycoprotein (7/33), NSP3 (6/33), RdRp/NSP12 (4/33), NSP2 (2/33) and N (2/33). Non-synonymous mutations were found to be 3.4 times more prevalent than synonymous mutations. We classified the Indian isolates into 22 groups based on the co-existing mutations. Phylogenetic analyses revealed that representative strain of each group divided themselves into various sub-clades within their respective clades, based on the presence of unique co-existing mutations. India was dominated by A2a clade (55.60%) followed by A3 (37.38%) and B (7%), but exhibited heterogeneous distribution among various geographical regions. The A2a clade mostly predominated in East India, Western India and Central India, whereas A3 clade prevailed in South and North India. In conclusion, this study highlights the divergent evolution of SARS-CoV-2 strains and co-circulation of multiple clades in India. Monitoring of the emerging mutations would pave ways for vaccine formulation and designing of antiviral drugs.

Genomic surveillance and phylodynamic analyses reveal emergence of novel mutation and co-mutation patterns within SARS-CoV2 variants prevalent in India

“…across Indian states and union territories compared over the three time terms. We observed a large number of non-clade defining mutations to co-occur within SARS-CoV2 strains from the states and union territories during the 'Term2' and 'Term3' which is consistent with earlier reports based on the sequences collected mostly in 'Term1' period (17). Consequently, a larger number of unique combinations among these cooccurred mutations were appeared during the latter half of the year 2020.…”

“…Several thousands of whole-genome sequences of the SARS-CoV2 from various parts of the country have been sequenced and subsequently deposited in global databases such as GISAID (16). Multiple works from India have highlighted the genomic diversity and the phylogenetic profiles of the prevalent strains in the country (7,17). However, more than 75% of the SARS-CoV2 sequences (2521 out of 3277 complete genomes from India) were deposited in the latter half of the year 2020.…”

SARS-CoV-2 presented moderately during two episodes of the infection with lack of antibody responses

“…The acquisitive features usually lead to severe infectivity, altered virulence and better transmissibility besides antigenic shifting which facilitates host immunity escape. This also might compromise the vaccines efficacy and antiviral drugs ( Sadat et al, 2021 ; Sarkar et al, 2021 ).…”

Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19

“…The ACE2 protein belongs to the membrane-bound carboxypeptidase family and is responsible for converting angiotensin II to angiotensin [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. It is widely distributed throughout the human body, with supramaximal levels in the small intestine, testis, kidneys, heart, thyroid, adipose tissue, colon, liver, bladder, adrenal glands and lungs (mainly in type II alveolar cells) and macrophages.…”

“…Finally, only in December 2020, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom and the Food and Drug Administration (FDA) in the United States of America (USA) authorized the emergency use of Pfizer/BioNTech’s and Moderna’s vaccines against COVID-19 [ 5 ]. Nevertheless, worldwide vaccine plans are yet to be implemented and novel mutations of the SARS-CoV-2 are rapidly emerging [ 6 , 7 ] demanding continuous research on therapeutics to manage COVID-19. By the end of February 2021, the number of global deaths related to COVID-19 was close to 2.5 million.…”