ArticleVirologica Sinica2024
Bis-benzylisoquinoline alkaloids inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy.
Article in Virologica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Transient receptor potential channels inChannels (Austin, Tex.) · 2026Review
- Cross-Family Mechanistic Analysis of Plant Alkaloids Against Neglected Arboviruses and Related RNA Viruses.Molecules (Basel, Switzerland) · 2026Review
- A novel small molecule inhibitor targeting KHSRP methylation suppresses colon cancer progression.Acta pharmaceutica Sinica. B · 2026Article
- Targeting virus-interacting host ion channels as a novel antiviral strategy.Acta pharmacologica Sinica · 2026Review
- Discovery of Two Novel Scorpion Venom Peptides Activating TRPML2 to Impair ZIKV Internalization.Toxins · 2026Article
- Smart Nanoparticles Disrupting Energy Supply through Triple Mechanisms to Kill Tumors via Dual Disruption of Mitochondria and Lysosomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fangchinoline (2021-2026): A Multitarget Bisbenzylisoquinoline Alkaloid With Emerging Anti-Infective Potential.Journal of tropical medicine · 2026Review
- Virtual reality and cheminformatics-driven discovery of a potential broad-spectrum natural antagonist against flaviviral methyltransferases and its cytotoxicity evaluation.Journal of computer-aided molecular design · 2025Article
- Virucidal activity of Cannabis sativa L. (hemp) root and stem extracts against Japanese encephalitis virus: role of stigmasterol.Archives of virology · 2025Article
- DENV-2 3'UTR dumbbell structure is a critical factor for viral infection and dissemination inJournal of virology · 2025Article
- Bioactive Plant-Derived Compounds as Novel Perspectives in Oral Cancer Alternative Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Bisbenzylisoquinoline alkaloids inhibit influenza virus replication by disrupting endosomal acidification.Virology journal · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
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Abstract
Flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV), represent a substantial public health challenge as there are currently no approved treatments available. Here, we investigated the antiviral effects of bis-benzylisoquinoline alkaloids (BBAs) on flavivirus infections. We evaluated five specific BBAs-berbamine, tetrandrine, iso-tetrandrine, fangchinoline, and cepharanthine-and found that they effectively inhibited infections by ZIKV, DENV, or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle. Furthermore, we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes, causing lysosomal pH alkalization. Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels, leading to lysosomal dysfunction and reducing the expression of NCAM1, a key receptor for the entry of ZIKV into cells, thereby decreasing cells susceptibility to ZIKV infection. Additionally, BBAs inhibited the fusion of autophagosomes and lysosomes, significantly reducing viral RNA replication. Collectively, our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy, respectively, underscoring the potential of BBAs as therapeutic agents against flavivirus infections.
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