Betrixaban Activates cGAS and ERVs to Promote Dual Nucleic-Sensing Antiviral Immunity

ABSTRACT: Broad-spectrum host-directed antivirals are urgently needed, as virus-targeted drugs often suffer from narrow specificity and rapid resistance. Here, we reported that Betrixaban (BT), an FDA-approved oral Factor Xa inhibitor, induced a robust antiviral state through dual innate immune pathways. Mechanistically, we identified BT as the first small-molecule directly bound and activated the DNA sensor cGAS to induce cGAMP production. Concurrently, BT inhibited histone deacetylases (HDACs), leading to chromatin de-repression of endogenous retroviruses (ERVs) and production of immunostimulatory double-stranded RNA (dsRNA) that engaged RIG-I/MDA5. These combined signal cascades triggered strong type I interferon responses and conferred broad-spectrum antiviral protection against RNA and DNA viru

SUBMITTER: Xingyu Chen 

PROVIDER: S-SCDT-10_1038-S44321-025-00356-7 | biostudies-other |

REPOSITORIES: biostudies-other