Researchers reported that combining inhibitors targeting SARS‑CoV‑2 papain‑like protease (PLpro) with host RIPK1 inhibitors produced potent, synergistic antiviral effects in a mouse COVID‑19 model. The team published preclinical results showing combination therapy reduced viral loads and improved survival compared with single agents. The report, appearing in Acta Pharmaceutica Sinica B, indicates dual targeting of viral proteases and host inflammatory kinases can both suppress replication and blunt pathogenic host responses. The compounds demonstrated favorable safety signals in the small‑animal study but remain preclinical. The finding suggests a two‑pronged antiviral strategy—direct antiviral plus host‑directed immunomodulation—could extend therapeutic choices against variants that partially escape current direct‑acting antivirals. Companies developing PLpro inhibitors or RIPK1 modulators may find routes to rapid combination development, but translation will require detailed toxicology and human efficacy trials.