1. Natural Polyphenols Inhibit the Dimerization of the SARS-CoV-2 Main Protease: The Case of Fortunellin and Its Structural Analogs
- Author
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Athanasios A. Panagiotopoulos, Ioannis Karakasiliotis, Danai-Maria Kotzampasi, Marios Dimitriou, George Sourvinos, Marilena Kampa, Stergios Pirintsos, Elias Castanas, and Vangelis Daskalakis
- Subjects
SARS-CoV-2 ,COVID-19 ,molecular simulations ,metadynamics ,natural products ,Organic chemistry ,QD241-441 - Abstract
3CL-Pro is the SARS-CoV-2 main protease (MPro). It acts as a homodimer to cleave the large polyprotein 1ab transcript into proteins that are necessary for viral growth and replication. 3CL-Pro has been one of the most studied SARS-CoV-2 proteins and a main target of therapeutics. A number of drug candidates have been reported, including natural products. Here, we employ elaborate computational methods to explore the dimerization of the 3CL-Pro protein, and we formulate a computational context to identify potential inhibitors of this process. We report that fortunellin (acacetin 7-O-neohesperidoside), a natural flavonoid O-glycoside, and its structural analogs are potent inhibitors of 3CL-Pro dimerization, inhibiting viral plaque formation in vitro. We thus propose a novel basis for the search of pharmaceuticals as well as dietary supplements in the fight against SARS-CoV-2 and COVID-19.
- Published
- 2021
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