Natural Polyphenols Inhibit the Dimerization of the SARS-CoV-2 Main Protease: The Case of Fortunellin and Its Structural Analogs

Molecules

Vangelis Daskalakis¹  Marios Dimitriou²  Ioannis Karakasiliotis²  Danai-Maria Kotzampasi³  Athanasios A. Panagiotopoulos³  Marilena Kampa³  Elias Castanas³  George Sourvinos⁴  Stergios Pirintsos⁵ 

[1] Department of Chemical Engineering, Cyprus University of Technology, 3603 Limassol, Cyprus;Laboratory of Biology, School of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece;Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, 71003 Heraklion, Greece;Laboratory of Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece;Nature Crete Pharmaceuticals, 71305 Heraklion, Greece;

关键词: SARS-CoV-2;    COVID-19;    molecular simulations;    metadynamics;    natural products;   

DOI  :  10.3390/molecules26196068

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown