Summary 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.
Jianfa Qiu, Xuecong Xing, Jing-Feng Wang et al.· iScience· 0 citations
Summary Age-associated organ dysfunction markedly impairs quality of life and increases mortality in older adults. Aging frequently results in compromised mitochondrial function in organs with high energy demands, such as skeletal muscle, the brain, heart, kidneys, and liver. This impairment leads to excessive production of reactive oxygen species, increased inflammation, energy deficits, and aberrant cellular signaling, collectively fostering cellular senescence, and chronic diseases. Empirical research has demonstrated that regular physical exercise preserves mitochondrial integrity. This review summarizes common and specific responses to exercise in mitochondrial regulation across various organs and provides a comprehensive cross-organ analysis. The objective was to elucidate the molecular mechanisms through which exercise confers anti-aging effects and mitigates degenerative functional decline by restoring mitochondrial homeostasis. This review provides a theoretical foundation for developing targeted anti-aging interventions and for attenuating aging in multiple organs through lifestyle modifications.
Zhuoyang Zhou, Jianhong Gao, Minghui Wang et al.· iScience· 0 citations