ABSTRACT
The COVID-19 pandemic caused by SARS-CoV-2 results almost 3 M death worldwide and till continuing in spite of having several vaccine against the virus. One of the main reasons is the mutations occur in the virus to cope with the environment. Detail study of genomics and proteomics level of each components may help to combat the situation. Spike (S) protein that covers the surface of the virus helps in entry by encountering the host receptor Human Angiotensin-Converting Enzyme-2 (hACE-2) with other different roles. In this study, we accomplish our work with the mutations in receptor binding domain (RBD) of Spike (S) protein considering different aspects like the hACE-2 variants in human populations to get an idea about the varying infectivity of different strains for different population. Several other parameters affecting the viral infectivity and in different diseased condition were also studied which may guide to a better insight in developing future therapeutics.
ABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an enveloped RNA virus transmits by droplet infection thus affects the respiratory system. Different genomes have been reported globally for SARS-CoV-2 with moderate level of mutation which makes it harder to combat the virus. Mutational profiling and the relevant evolutionary aspect of coronavirus proteins namely spike glycoprotein, membrane protein, envelope protein, nucleoprotein, ORF1ab, ORF3a, ORF6, ORF7a, ORF7b and ORF8 were studied by in silico experiments. Clustering of the protein sequences and calculation of residue relative abundance were done to get an idea about the protein conservancy as well as finding out some representative sequences for phylogenetic and ancestral reconstruction. By mutational profiling and mutation analysis, the effect of mutations on the protein stability and their functional implication were studied. This study indicates the mutational effect on the proteins and their relevance in evolution, which directs us towards a better understanding of these variations and diversification of SARS-CoV-2 for useful future therapeutic study and thus aid in designing therapeutic agents keeping the highly variable regions in mind.
Subject(s)
COVID-19/genetics , Computer Simulation , Genome, Viral , Mutation , Phylogeny , SARS-CoV-2/genetics , Viral Proteins/genetics , HumansABSTRACT
COVID-19 caused by SARS-CoV-2 have become a global pandemic with serious rate of fatalities. SARS-CoV and MERS-CoV have also caused serious outbreak previously but the intensity was much lower than the ongoing SARS-CoV-2. The main infectivity factor of all the three viruses is the spike glycoprotein. In this study we have examined the intrinsic dynamics of the prefusion, lying state of trimeric S protein of these viruses through Normal Mode Analysis using Anisotropic Network Model. The dynamic modes of the S proteins of the aforementioned viruses were compared by root mean square inner product (RMSIP), spectral overlap and cosine correlation matrix. S proteins show homogenous correlated or anticorrelated motions among their domains but direction of Cα atom among the spike proteins show less similarity. SARS-CoV-2 spike shows high vertically upward motion of the receptor binding motif implying its propensity for binding with the receptor even in the lying state. MERS-CoV spike shows unique dynamical motion compared to the other two S protein indicated by low RMSIP, spectral overlap and cosine correlation value. This study will guide in developing common potential inhibitor molecules against closed state of spike protein of these viruses to prevent conformational switching from lying to standing state.