Betrixaban is a broad anti-virus inhibitor by activating innate immunity

The innate immune system serves as the first line of defense against viral infections. Type I interferon (IFN-I) signaling, in particular, plays a crucial role in mediating antiviral immunity. Here, we identify Betrixaban (BT), a novel small-molecule compound that activates innate immune responses, leading to broad-spectrum antiviral effects. BT induces IFN-β production and upregulates interferon-stimulated genes (ISGs), effectively suppressing the replication of multiple viruses, including vesicular stomatitis virus (VSV), herpes simplex virus type 1 (HSV-1), murine hepatitis virus strain A59 (MHV-A59), encephalomyocarditis virus (EMCV), and influenza A virus (IAV). BT's antiviral activity relies on innate immune activation, with IRF3 playing a key role. The antiviral effect was significantly reduced upon loss of ISGs induction, including Mx1 and Mx2. <i>In vivo</i>, BT treatment markedly induced IFNB1 expression across multiple mouse tissues and significantly inhibited viral replication in VSV-infected wild-type mice, confirming the essential role of innate antiviral immune activation. These findings establish BT as a potent stimulator of the innate immune system, demonstrating broad-spectrum antiviral potential and highlighting its promise as a therapeutic agent.