Targeting Viral Suppressor of RNAi for Combating SARS-CoV-2 Variants

RNA interference (RNAi) is a conserved cell-intrinsic antiviral mechanism in diverse eukaryotic organisms, including mammals, while many viruses encode viral suppressors of RNAi (VSRs) to evade the RNAi response, suggesting that targeting VSRs is a novel strategy to develop antiviral therapies.

In this study, we demonstrated that the dimerization is crucial or the VSR activity of SARS-CoV-2 nucleocapsid (N) protein. We designed a series of peptides specifically targeting the dimerization interface of N protein. Among them, a peptide designated GL directly interacted with the N protein, inhibiting its dimerization and thereby inactivating its VSR activity.