Pillar 10
Antiviral Strategies and Antiviral Therapeutics

This research project identifies berbamine dihydrochloride as a potent inhibitor of SARS-CoV-2 entry and replication in human intestinal epithelial cells. Excitingly, berbamine displayed pan-SARS-CoV-2 antiviral activity by targeting machinery of the host autophagy pathway, including a striking nanomolar potency against SARS-CoV-2 Omicron subvariants. This work demonstrates that berbamine, a molecule derived from traditional Chinese medicinal herbs and under investigation for its anti-cancer properties, is a promising option for a cost-effective, over-the-counter antiviral that could be fast-tracked to reach COVID-19 patients.

This work also provides exciting mechanistic insights into the antiviral functioning of berbamine and underlines the relevancy of using autophagy-targeting antivirals. Host-directed therapies like these are an exciting alternative to direct-acting antivirals because they are able to boost cell-intrinsic antiviral defenses with a low likelihood of the development of drug resistance. Importantly, our collaborative research on the natural product berbamine is unraveling the importance of natural resources in discovering nature-based medicines to fight emerging viruses and is paving the way for innovative drug treatments against COVID-19 variants.

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Berbamine suppresses intestinal SARS-CoV-2 infection via a BNIP3-dependent autophagy blockade. Alexandra P.M. Cloherty, Anusca G. Rader, Karishma S. Patel, Jimena Pérez-Vargas, Connor A.H. Thompson, Siobhan Ennis, Masahiro Nikura, Manon E. Wildenberg, Vanessa Muncan, Renée R.C.E. Schreurs, and François Jean. Emerging Microbes & Infections. 2023.04.17. https://www.tandfonline.com/doi/full/10.1080/22221751.2023.2195020