Publication date: Dec 10, 2024
Infections caused by coronaviruses are persistent threats to human health in recent decades, necessitating the development of innovative anti-coronaviral therapies. RNA interference (RNAi) is a conserved cell-intrinsic antiviral mechanism in diverse eukaryotic organisms, including mammals. To counteract, many viruses encode viral suppressors of RNAi (VSRs) to evade antiviral RNAi, implying that targeting VSRs could be a promising strategy to develop antiviral therapies. Here, we designed a series of peptides specifically targeting the SARS-CoV-2-encoded VSR, nucleocapsid (N) protein. Among these peptides, one designated GL directly interacts with N protein and inactivates its VSR activity, which unlocks a potent RNAi response and effectively inhibits SARS-CoV-2 replication. Moreover, GL exhibited RNAi-dependent antiviral effects not only against various SARS-CoV-2 variants, including Delta, Omicron BA. 5, XBB and JN. 1, but also against other coronaviruses such as HCoV-229E, HCoV-OC43 and mouse hepatitis virus. The in vivo anti-coronaviral activity of GL was also confirmed. Our findings indicate that the VSR-targeting peptide GL has the potential to be further developed as a broad-spectrum anti-coronaviral treatment, highlighting the functional importance and therapeutic potential of antiviral RNAi.
Concepts | Keywords |
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Antiviral | Activity |
Coronaviruses | Anti |
Decades | Antiviral |
Eukaryotic | Coronaviral |
Necessitating | Coronaviruses |
Cov | |
Including | |
Peptides | |
Rnai | |
Sars | |
Targeting | |
Therapies | |
Viral | |
Vsr | |
Vsrs |
Semantics
Type | Source | Name |
---|---|---|
disease | MESH | Infections |
disease | IDO | cell |
disease | IDO | protein |
disease | IDO | replication |