Nsp1 of SARS-CoV-2 Stimulates Host Translation Termination (preprint)

ABSTRACT

The Nsp1 protein of SARS-CoV-2 regulates the translation of host and viral mRNAs in cells. Nsp1 inhibits host translation initiation by binding to the entry channel of the 40S ribosome subunit. The structural study of SARS-CoV-2 Nsp1-ribosomal complexes reported post-termination 80S complex containing Nsp1 and the eRF1 and ABCE1 proteins. Considering the presence of Nsp1 in the post-termination 80S ribosomal complex simultaneously with eRF1, we hypothesized that Nsp1 may be involved in translation termination. We show the direct influence of Nsp1 on translation termination. Using a cell-free translation system and reconstituted in vitro translation system, we reveal that Nsp1 stimulates translation termination in the stop codon recognition stage. We identify that activity of Nsp1 in translation termination is localized in its N-terminal domain. The data obtained will enable an investigation of new classes of potential therapeutic agents from coronavirus infection competing with Nsp1 for binding with the termination complex.