EGCG as an anti-SARS-CoV-2 agent: Preventive versus therapeutic potential against original and mutant virus

• Published in: Biochimie Vol. 191; pp. 27 - 32
• Main Authors: Tsvetkov, Vladimir, Varizhuk, Anna, Kozlovskaya, Liubov, Shtro, Anna, Lebedeva, Olga, Komissarov, Andrey, Vedekhina, Tatjana, Manuvera, Valentin, Zubkova, Olga, Eremeev, Artem, Shustova, Elena, Pozmogova, Galina, Lioznov, Dmitry, Ishmukhametov, Aydar, Lazarev, Vassili, Lagarkova, Maria
• Format: Journal Article
• Language: English
• Published: France Elsevier B.V 01.12.2021; Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)
• Subjects: Animals; Antiviral Agents - pharmacology; Catechin - analogs & derivatives; Catechin - pharmacology; Chlorocebus aethiops; COVID-19 Drug Treatment; Epigallocatechin-3-gallate; Molecular Docking Simulation; Molecular Dynamics Simulation; Mutation; Preventive agent; SARS-CoV-2; SARS-CoV-2 - chemistry; SARS-CoV-2 - drug effects; SARS-CoV-2 - genetics; Spike viral proteins; Vero Cells; Viral Proteins - chemistry; Viral Proteins - metabolism; Virus Internalization - drug effects; SARS-CoV-2; Preventive agent; Spike viral proteins; Epigallocatechin-3-gallate
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2021.08.003

In the search for anti-SARS-CoV-2 drugs, much attention is given to safe and widely available native compounds. The green tea component epigallocatechin 3 gallate (EGCG) is particularly promising because it reportedly inhibits viral replication and viral entry in vitro. However, conclusive evidence for its predominant activity is needed. We tested EGCG effects on the native virus isolated from COVID-19 patients in two independent series of experiments using VERO cells and two different treatment schemes in each series. The results confirmed modest cytotoxicity of EGCG and its substantial antiviral activity. The preincubation scheme aimed at infection prevention has proven particularly beneficial. We complemented that finding with a detailed investigation of EGCG interactions with viral S-protein subunits, including S2, RBD, and the RBD mutant harboring the N501Y mutation. Molecular modeling experiments revealed N501Y-specific stacking interactions in the RBD-ACE2 complex and provided insight into EGCG interference with the complex formation. Together, these findings provide a molecular basis for the observed EGCG effects and reinforce its prospects in COVID-19 prevention therapy. •Epigallocatechin-3-gallate (EGCG) prevents SARS-CoV-2 infection in vitro.•Inhibitory assays with the live virus support pronounced protective activity of EGCG.•EGCG interacts with spike proteins of both original and mutant (B.1.1.7) SARS-CoV-2 variants.