Characterizing genomic variants and mutations in SARS-CoV-2 proteins from Indian isolates

Jayanta Kumar Das; Antara Sengupta; Pabitra Pal Choudhury; Swarup Roy

doi:10.1016/j.genrep.2021.101044

Characterizing genomic variants and mutations in SARS-CoV-2 proteins from Indian isolates

Gene Rep. 2021 Dec:25:101044. doi: 10.1016/j.genrep.2021.101044. Epub 2021 Feb 19.

Authors

Jayanta Kumar Das¹, Antara Sengupta², Pabitra Pal Choudhury³, Swarup Roy⁴

Affiliations

¹ Department of Pediatrics, School of Medicine, Johns Hopkins University, MD 21205, USA.
² Department of Computer Science and Engineering, University of Calcutta, India.
³ Applied Statistics Unit, Indian Statistical Institute, Kolkata 700108, India.
⁴ Network Reconstruction & Analysis (NetRA Lab), Department of Computer Applications, Sikkim University, Sikkim 737102, India.

Abstract

SARS-CoV-2 is mutating and creating divergent variants by altering the composition of essential constituent proteins. Pharmacologically, it is crucial to understand the diverse mechanism of mutations for stable vaccine or anti-viral drug design. Our current study concentrates on all the constituent proteins of 469 SARS-CoV-2 genome samples, derived from Indian patients. However, the study may easily be extended to the samples across the globe. We perform clustering analysis towards identifying unique variants in each of the SARS-CoV-2 proteins. A total of 536 mutated positions within the coding regions of SARS-CoV-2 proteins are detected among the identified variants from Indian isolates. We quantify mutations by focusing on the unique variants of each SARS-CoV-2 protein. We report the average number of mutation per variant, percentage of mutated positions, synonymous and non-synonymous mutations, mutations occurring in three codon positions and so on. Our study reveals the most susceptible six (06) proteins, which are ORF1ab, Spike (S), Nucleocapsid (N), ORF3a, ORF7a, and ORF8. Several non-synonymous substitutions are observed to be unique in different SARS-CoV-2 proteins. A total of 57 possible deleterious amino acid substitutions are predicted, which may impact on the protein functions. Several mutations show a large decrease in protein stability and are observed in putative functional domains of the proteins that might have some role in disease pathogenesis. We observe a good number of physicochemical property change during above deleterious substitutions.

Keywords: AA, amino acid; COVID-19; CP, codon position; CTD, C-terminal domain; CoV, coronaviruses; Codon position; Deleterious substitutions; Functional domain; HR, heptapeptide repeat; Mut, mutation; NS, non-synonymous; NTD, N-terminal domain; Non-synonymous mutations; Protein stability; SARS, severe acute respiratory syndrome; Syn, synonymous; TM, transmembrane domain.