SARS-CoV-2 nsp15 enhances viral virulence by subverting host antiviral defenses.

doi:10.1073/pnas.2426528122

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Article

SARS-CoV-2 nsp15 enhances viral virulence by subverting host antiviral defenses.

Proceedings of the National Academy of Sciences of the United States of America - 17 Jun 2025

Caobi Allen, Su Chia-Ming, Beusch Christian M, Kenney Devin, Darling Tamarand L, Feng Shuchen, Semaan Marc, Wacquiez Alan, Sanders Nathan L, Tully Ena S, Chen Da-Yuan, Evdokimova Monika, Ding Zhen, Jones Dakota, Alysandratos Konstantinos-Dionysios, Mizgerd Joseph P, Kirchdoerfer Robert N, Kotton Darrell N, Douam Florian, Crossland Nicholas A, Boon Adrianus C M, Gordon David E, Baker Susan C, Saeed Mohsan

Abstract excerpt

SARS-CoV-2 encodes numerous virulence factors, yet their precise mechanisms of action remain unknown. We provide evidence that the SARS-CoV-2 nonstructural protein 15 (nsp15) enhances viral virulence by suppressing the production of viral double-stranded (dsRNA), a potent inducer of antiviral signaling. The viral variants lacking nsp15 endoribonuclease activity elicited higher innate immune responses and...

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Identifiers

PMID: 40504150
DOI: 10.1073/pnas.2426528122
PMCID: PMC12184426

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