Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight

Abstract

A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. In this study, we have made an attempt to investigate the SARS-CoV-2 genome reported from 13 different countries, identification of mutations in major coronavirus proteins of these different SARS-CoV-2 genomes and compared with SARS-CoV. These thirteen complete genome sequences of SARS-CoV-2 showed high identity (>99%) to each other, while they shared 82% identity with SARS-CoV. Here, we performed a very systematic mutational analysis of SARS-CoV-2 genomes from different geographical locations, which enabled us to identify numerous unique features of this viral genome. This includes several important country-specific unique mutations in the major proteins of SARS-CoV-2 namely, replicase polyprotein, spike glycoprotein, envelope protein and nucleocapsid protein. Indian strain showed mutation in spike glycoprotein at R408I and in replicase polyprotein at I671T, P2144S and A2798V,. While the spike protein of Spain & South Korea carried F797C and S221W mutation, respectively. Likewise, several important country specific mutations were analyzed. The effect of mutations of these major proteins were also investigated using various in silico approaches. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. It was found that the R60C mutation in Mpro affects the protein dynamics, thereby, affecting the binding of inhibitor within its active site. The implications of mutation on structural characteristics were determined. The information provided in this manuscript holds

Sensitivity evaluation of 2019 novel coronavirus (SARS-CoV-2) RT-PCR detection kits and strategy to reduce false negative

“…In addition, multiple mutations were detected over the entire genomes of SARS-CoV-2 [43][44][45]. Variations are speculated to influence the rate of disease transmission and mortality [6,30,46] and also that the false-negative rate might be elevated if the mutation occurs at the current target genes of SARS-CoV-2. Except for the variations found throughout the genome, mutations of SARS-CoV-2 virus were also found at the primer-or probe-binding sites [47], which might lower the sensitivity of the current targeting genes.…”

Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity

“…Since then, the R408I mutant has attracted research attention from a significant number of researchers. Both computational and experimental studies have been performed to further investigate its molecular characteristics and potential immune effects [31][32][33][34][35][36][37][38] . In addition, commercial synthesis of the R408I recombinant RBD protein has been offered by serval companies (Acro Biosystems, Creative Dianostics, SinoBiological, and Creative Biolabs) for immuno-binding and diagnostic testing.…”

Isolating SARS-CoV-2 Strains From Countries in the Same Meridian: Genome Evolutionary Analysis

“…Furthermore, a comparison of viral genomes of SARS-CoV-2 strains from 13 countries identified differences in the protein-coding sequences. For example, an Indian strain showed a mutation in the spike glycoprotein at R408I and in the replicase polyprotein at I671T, P2144S, and A2798V, whereas the spike protein of Spain and South Korean strains carried an F797C and a S221W mutation, respectively [ 27 ]. Moreover, recently conducted integrative analyses of SARS-CoV-2 genomes of strains from different geographical locations reveal unique features that are potentially consequential to host-virus interaction and pathogenesis [ 28 ].…”