In silico tracking of SARS-CoV-2 Nsp1 structural variants in helix-turn-helix motif

Abstract

SARS-CoV-2 non-structural protein 1 (Nsp1) is a virulence factor that inhibits the innate immune response and translation of host mRNAs. Despite the relevance of Nsp1, few studies have been conducted to understand the effect of mutations on Nsp1 structure and function. Here, we provide a molecular dynamics simulation of SARS-CoV-2 and SARS-CoV-1 Nsp1 conformational changes. Our data supports the idea that SARS-CoV-2 Nsp1 has a less compact structure than SARS-CoV-1 Nsp1. Moreover, several mutations in the helix-loop-helix motif of Nsp1 C-terminal that may affect the interactions of the Nsp1-ribosome complex were investigated. Disordered regions in Nsp1 probably affect host-virus interactions, cross-species transmission, and virus-host range. Overall, these findings reinforce the importance of studying Nsp1 conformational changes in new variants and its effect on virulence of SARS-CoV-2, by altering inhibition potency of host mRNA translation efficiency.

Next-Generation Bioinformatics Approaches and Resources for Coronavirus Vaccine Discovery and Development—A Perspective Review

“…In an in silico approach to track SARS-CoV-2 Nsp1 structural variants, Rezaei et al exploited the SARS-CoV-2 proteome 3D database to identify and retrieve the complex structure of the Nsp1 with the ribosomal 40S subunit and associated interaction details [ 28 ].…”