Analysis of Indian SARS-CoV-2 Genomes Reveals Prevalence of D614G Mutation in Spike Protein Predicting an Increase in Interaction With TMPRSS2 and Virus Infectivity

Abstract

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has emerged as a global pandemic worldwide. In this study, we used ARTIC primers–based amplicon sequencing to profile 225 SARS-CoV-2 genomes from India. Phylogenetic analysis of 202 high-quality assemblies identified the presence of all the five reported clades 19A, 19B, 20A, 20B, and 20C in the population. The analyses revealed Europe and Southeast Asia as two major routes for introduction of the disease in India followed by local transmission. Interestingly, the19B clade was found to be more prevalent in our sequenced genomes (17%) compared to other genomes reported so far from India. Haplotype network analysis showed evolution of 19A and 19B clades in parallel from predominantly Gujarat state in India, suggesting it to be one of the major routes of disease transmission in India during the months of March and April, whereas 20B and 20C appeared to evolve from 20A. At the same time, 20A and 20B clades depicted prevalence of four common mutations 241 C > T in 5′ UTR, P4715L, F942F along with D614G in the Spike protein. D614G mutation has been reported to increase virus shedding and infectivity. Our molecular modeling and docking analysis identified that D614G mutation resulted in enhanced affinity of Spike S1–S2 hinge region with TMPRSS2 protease, possibly the reason for increased shedding of S1 domain in G614 as compared to D614. Moreover, we also observed an increased concordance of G614 mutation with the viral load, as evident from decreased Ct value of Spike and the ORF1ab gene.

Respiratory Co-Infections: Modulators of SARS-CoV-2 Patients’ Clinical Sub-Phenotype

“…Another missense SNP at position C6312A within Nsp 3 protein was observed in 99% of the viral isolates in our sample set. This mutation is found to be predominant in viral isolates from India and is a defining variant for clade I/A3i (Raghav et al, 2020).…”

Global variation in SARS-CoV-2 proteome and its implication in pre-lockdown emergence and dissemination of 5 dominant SARS-CoV-2 clades

“…As SARS-CoV-2 variants having Spike:D614G mutation (which has enhanced infectivity and transmissibility ( Korber et al, 2020 ; Zhang et al, 2020c ; Plante et al, 2021 ; Gobeil et al, 2021 ; Raghav et al, 2020 )) have conquered the wild-type across the globe, it is important to analyze the occurrence of high and moderate recurrent mutations along with Spike:D614G. Luckily, the availability of the mutations present in the SARS-CoV-2 proteome enables the understanding of the prevalence of certain mutations along with Spike:D614G (TableSD29.xlsx).…”

Investigating the Links Between Vaccination Against COVID-19 and Public Attitudes Toward Protective Countermeasures: Implications for Public Health

“…By June 15, 2021, the WHO had been officially notified about mutations of SARS-CoV-2 since its emergence. The variants of concern are mainly related to the B.1.1.7 mutation in United Kingdom (Alpha variant), the B.1.351 mutation in South Africa (Beta variant), the P.1 mutation in Brazil (Gamma variant), and the B.1.617.2 mutation in India (Delta variant) ( 41 , 42 ). Epsilon, Zeta, Eta, Theta, Iota, Kappa, and Lambda are variants of interest named by the WHO.…”