ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Targeting viral suppressor of RNAi confers anti-coronaviral activity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Rational Design of Broad-Spectrum Anti-Enteroviral Molecular Glues Targeting Enteroviral RNAi Suppressors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Host-virus molecular arms race: RNAi-mediated antiviral defense and viral suppressor of RNAi.Cell insight · 2025Review
- Getting the host antiviral machinery back on track: Targeting viral suppressors of RNA interference.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 severe acute respiratory syndrome coronavirus 2 (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 human coronavirus (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.
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