ArticleNational science review2025
Phytochemical alkaloids orchestrate immunometabolism against viral infections.
Article in National science review, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The bidirectional immunoregulatory effects of Traditional Chinese Medicine on the cGAS-STING signaling pathway and their translational prospects.Chinese medicine · 2026Review
- Antiviral Efficacy of the Traditional Chinese Medicine Mixture Yuanzhixingrenheji Against Human Adenovirus-7 In Vitro, In Vivo, and in a Clinical Retrospective Study.Pathogens (Basel, Switzerland) · 2026Article
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Authors and funding
16 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The role of cholesterol metabolism in antiviral immunity has been established, but if and how this cholesterol-mediated immunometabolism can be regulated by specific small molecules is of particular interest in the quest for novel antiviral therapeutics. Here, we first demonstrate that NPC1 is the key cholesterol transporter for suppressing viral replication by changing cholesterol metabolism and triggering the innate immune response via systemic analyses of all possible cholesterol transporters. We then use the Connectivity Map (CMap), a systematic methodology for identifying functional connections between genetic perturbations and drug actions, to screen NPC1 inhibitors, and found that bis-benzylisoquinoline alkaloids (BBAs) exhibit high efficacy in the inhibition of viral infections. Among all potent BBAs that we tested, tetrandrine (Tet) is the most effective, by directly binding to NPC1 and inducing lysosomal cholesterol accumulation in order to resist viral entries. Through the NPC1-STING interface mechanism, Tet further blocks STING lysosomal degradation which leads to boosting of the interferon-based antiviral response against multiple viruses both
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