Phylogenomic analysis of SARS-CoV-2 genomes from western India reveals unique linked mutations

Abstract

India has become the third worst-hit nation by the COVID-19 pandemic caused by the SARS-CoV-2 virus. Here, we investigated the molecular, phylogenomic, and evolutionary dynamics of SARS-CoV-2 in western India, the most affected region of the country. A total of 90 genomes were sequenced. Four nucleotide variants, namely C241T, C3037T, C14408T (Pro4715Leu), and A23403G (Asp614Gly), located at 5'UTR, Orf1a, Orf1b, and Spike protein regions of the genome, respectively, were predominant and ubiquitous (90%). Phylogenetic analysis of the genomes revealed four distinct clusters, formed owing to different variants. The major cluster (cluster 4) is distinguished by mutations C313T, C5700A, G28881A are unique patterns and observed in 45% of samples. We thus report a newly emerging pattern of linked mutations. The predominance of these linked mutations suggests that they are likely a part of the viral fitness landscape. A novel and distinct pattern of mutations in the viral strains of each of the districts was observed. The Satara district viral strains showed mutations primarily at the 3′ end of the genome, while Nashik district viral strains displayed mutations at the 5′ end of the genome. Characterization of Pune strains showed that a novel variant has overtaken the other strains. Examination of the frequency of three mutations i.e., C313T, C5700A, G28881A in symptomatic versus asymptomatic patients indicated an increased occurrence in symptomatic cases, which is more prominent in females. The age-wise specific pattern of mutation is observed. Mutations C18877T, G20326A, G24794T, G25563T, G26152T, and C26735T are found in more than 30% study samples in the age group of 10-25. Intriguingly, these mutations are not detected in the higher age range 61-80. These findings portray the prevalence of unique linked mutations in SARS-CoV-2 in western India and their prevalence in symptomatic patients.

Mutational landscape and dominant lineages in the SARS-CoV-2 infections in the state of Telangana, India

“…Apart from these four mutations, the nsp3 protein region within ORF1a also displayed a higher frequency of mutations, G4354A, A4372G, C5700A, C6027T, C6573T, the latter three being missense mutations. Of these, C5700 along with a silent C313T mutation has been reported to co-occur in samples collected from Western state of Maharashtra, India 16 . The nsp4 and nsp5 proteins each harbored one high frequency missense mutation each namely C9693T and C10815T, respectively.…”

Phase II Clinical trial for Evaluation of BCG as potential therapy for COVID-19

“…Such a reduction in viral titers on BCG administration have also been seen in case of other viruses like respiratory syncytial virus, influenza A virus and herpes simplex virus type 2 possibly through macrophage activation [29-31]. However this sensitivity was not seen in later half of the study indicating that perhaps there were 2 strains of the virus as suggested by Paul et al [32]. Sequencing the virus strains is underway at present which will make this clear and could possibly provide an explanation of the heterogeneous nature of Covid-19 progression and outcomes in various populations and/or in the same population /center at different times.…”

A comprehensive profile of genomic variations in the SARS-CoV-2 isolates from the state of Telangana, India

“…G4354A, A4372G, C5700A, C6027T, C6573T, the latter three being missense mutations. Of these, C5700 along with a silent C313T mutation has been reported to co-occur in samples collected from the Western state of Maharashtra, India [31]. The nsp4 and nsp5 proteins each harboured one high-frequency missense mutation each namely C9693T and C10815T, respectively.…”