Eight-amino-acid sequence at the N-terminus of SARS-CoV-2 nsp1 is involved in stabilizing viral genome replication

Coronavirus disease 19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enveloped virus with a single-stranded positive-sense ribonucleic acid (RNA) genome. The CoV non-structural protein (nsp) 1 is a multifunctional protein that undergoes translation shutoff, messenger RNA (mRNA) cleavage, and RNA binding. The C -terminal region is involved in translational shutoff and RNA cleavage. The N-terminal region of SARS-CoV-2 nsp1 is highly conserved among isolated SARS-CoV-2 variants. However, the I-004 variant, isolated during the early SARS-CoV-2 pandemic, lost eight amino acids in the nsp1 region. In this study, we showed that the eight amino acids are important for viral replication in infected interferonincompetent cells and that the recombinant virus that lost these amino acids had low pathogenicity in the lungs of hamster models. The loss of eight amino acids-induced mutations occurred in the 5 ' untranslated region (UTR), suggesting that nsp1 contributes to the stability of the viral genome during replication.