Scientists identified small‑molecule inhibitors of SARS‑CoV‑2 papain‑like protease (PLpro) and the host kinase RIPK1 that, when combined, produced potent synergistic antiviral effects in a mouse COVID‑19 model. The study, published in Acta Pharmaceutica Sinica B, reports improved viral clearance and reduced pathology compared with single‑agent treatments, suggesting a combination strategy that targets both viral replication and host inflammatory signaling. The preclinical results support advancing these inhibitors toward translational studies and highlight a dual‑target approach that could retain activity against emerging variants by pairing direct‑acting antivirals with host‑directed modulators.