Targeting Viral Suppressor of RNAi confers anti-coronaviral activity.

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
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

Original Article

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