tetano
Editor, Senior Moderator
iScience
. 2026 Jul 20;29(8):116899.
doi: 10.1016/j.isci.2026.116899. eCollection 2026 Aug 21.
A functional genomics-pharmacotranscriptomics framework identifies host-directed anti-influenza agents
Jianfa Qiu[SUP] 1 2 [/SUP], Xuecong Xing[SUP] 1 2 [/SUP], Jingfeng Wang[SUP] 2 [/SUP], Weijing Yuan[SUP] 2 [/SUP], Xiaorong Li[SUP] 2 [/SUP], Aiping Wu[SUP] 2 [/SUP], Zhimin Gu[SUP] 2 [/SUP], Zhuo Zhou[SUP] 2 [/SUP], Jianwei Wang[SUP] 1 3 [/SUP]
Affiliations
Influenza A virus (IAV) remains a major threat to human and animal health, while the emergence of drug-resistant strains necessitates new antiviral strategies. Here, we developed an integrative host-directed drug discovery framework combining functional genomics and pharmacotranscriptomics. By aggregating published genome-wide screens, we assigned host genes functional scores reflecting their effects on IAV replication and used these scores to estimate the antiviral status of host cells. Screening nearly 20,000 drug-induced transcriptional signatures identified compounds that shift host gene expression toward an antiviral state. Among 54 selected hits, 18 showed anti-IAV activity. Notably, lithocholic acid and ALW-II-49-7 inhibited viral replication in vitro and protected mice from lethal infection in vivo. This host-targeted framework provides a systematic and scalable strategy for discovering antivirals that are less susceptible to resistance and potentially applicable to other rapidly evolving pathogens.
Keywords: antiviral status; drug repurposing; functional genomics; influenza A virus.
. 2026 Jul 20;29(8):116899.
doi: 10.1016/j.isci.2026.116899. eCollection 2026 Aug 21.
A functional genomics-pharmacotranscriptomics framework identifies host-directed anti-influenza agents
Jianfa Qiu[SUP] 1 2 [/SUP], Xuecong Xing[SUP] 1 2 [/SUP], Jingfeng Wang[SUP] 2 [/SUP], Weijing Yuan[SUP] 2 [/SUP], Xiaorong Li[SUP] 2 [/SUP], Aiping Wu[SUP] 2 [/SUP], Zhimin Gu[SUP] 2 [/SUP], Zhuo Zhou[SUP] 2 [/SUP], Jianwei Wang[SUP] 1 3 [/SUP]
Affiliations
- PMID: 42495532
- PMCID: PMC13393819
- DOI: 10.1016/j.isci.2026.116899
Influenza A virus (IAV) remains a major threat to human and animal health, while the emergence of drug-resistant strains necessitates new antiviral strategies. Here, we developed an integrative host-directed drug discovery framework combining functional genomics and pharmacotranscriptomics. By aggregating published genome-wide screens, we assigned host genes functional scores reflecting their effects on IAV replication and used these scores to estimate the antiviral status of host cells. Screening nearly 20,000 drug-induced transcriptional signatures identified compounds that shift host gene expression toward an antiviral state. Among 54 selected hits, 18 showed anti-IAV activity. Notably, lithocholic acid and ALW-II-49-7 inhibited viral replication in vitro and protected mice from lethal infection in vivo. This host-targeted framework provides a systematic and scalable strategy for discovering antivirals that are less susceptible to resistance and potentially applicable to other rapidly evolving pathogens.
Keywords: antiviral status; drug repurposing; functional genomics; influenza A virus.