Host‐Directed Antiviral Activity of SB2960 Through Selective Induction and Remodeling of Stress Granules

Abstract The increasing prevalence of emerging infectious diseases highlights the urgent need for broad‐spectrum antiviral therapeutics. Here, the discovery of SB2960, a small molecule, is reported that promotes stress granule (SG) formation and exhibits potent antiviral activity across diverse viral species. SB2960 suppresses viral replication with minimal cytotoxicity by modulating host antiviral immune responses. Target identification studies reveal that SB2960 engages receptor for activated protein C kinase 1 (RACK1), a key regulator of SG dynamics. Integrated transcriptomic and proteomic analyses further demonstrate that SB2960 alters the composition of SG and modulates the expression of antiviral genes. These findings establish SB2960 as a promising host‐directed broad‐spectrum antiviral agent and a valuable probe for investigating SG biology in the context of viral infection.