Comparative analysis of non structural protein 1 of SARS-CoV2 with SARS-CoV1 and MERS-CoV: An in silico study

Abstract

The recently emerged SARS-CoV2 caused a major pandemic of coronavirus disease (COVID-19). Non structural protein 1 (nsp1) is found in all beta coronavirus that causes several severe respiratory diseases. This protein is considered as a virulence factor and has an important role in pathogenesis. This study aims to elucidate the structural conformations of non structural protein 1 (nsp1), prediction of epitope sites and identification of important residues for targeted therapy against COVID-19. In this study, molecular modelling coupled with molecular dynamics simulations were performed to analyse the conformational change of nsp1 of SARS-CoV1, SARS-CoV2 and MERS-CoV at molecular level. Principal component analysis escorted by free energy landscape revealed that SARS-CoV2 nsp1 protein shows greater flexibility, compared to SARS-CoV1 and MERS-CoV nsp1. From the sequence alignment, it was observed that 28 mutations are present in SERS-CoV2 nsp1 protein compared to SERS-CoV1 nsp1. Several B-cell and T-cell epitopes were identified by immunoinformatics approach. SARS-CoV2 nsp1 protein binds with the interface region of the palm and finger domain of POLA1 by using hydrogen bond and salt bridge interactions. These findings can be used to develop therapeutics specific against COVID-19.