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

Abstract

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.

SARS-CoV-2 neutralizing activity of polyphenols in a special green tea extract preparation

“…It has also been shown in vitro that EGCG treatment decreased 3CL-protease activity of HCoV-OC43 and HCoV-229E, as well as HCoV-OC43-induced cytotoxicity ( Liu et al, 2021b , Jang et al, 2021 ). Other studies have shown that EGCG effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor ( Joseph et al, 2021 ; Liu et al, 2021a ) and EGCG has been suggested for prevention COVID-19 ( Tsvetkov et al, 2021 ). It was also shown, that EGCG blocks not only the entry of SARS-CoV-2, but also MERS- and SARS-CoV pseudo-typed lentiviral vectors and inhibited virus infections in vitro ( Henss et al, 2021 ).…”

Potential of green tea EGCG in neutralizing SARS-CoV-2 Omicron variant with greater tropism toward the upper respiratory tract

“… The IC 50 of EGCG for CPE was 5.0 μM and CPE was almost fully inhibited by EGCG at the doses of 25 and 50 μM. Tsvetkov et al (2021) Partial EGCG treatment in which SARS-CoV-2 was pre-incubated with EGCG prior to the infection. The IC 50 of EGCG for CPE was 0.6 μM.…”

“… The IC 50 of EGCG for plaque formation was 4.0 μM and the plaque formation was highly inhibited by EGCG at a dose of 20 μM. Tsvetkov et al (2021) Partial EGCG treatment in which SARS-CoV-2 was pre-incubated with EGCG prior to the infection and EGCG was added to cells after infection. The IC 50 of EGCG for plaque formation was 3.8 μM and the plaque formation was fully inhibited by EGCG at a dose of 44 μM, which did not cause cytotoxicity after a 48-h incubation.…”

“…Tsvetkov et al examined the effect of partial EGCG treatment in which EGCG was added to Vero cells prior to the infection ( Tsvetkov et al, 2021 ). After 2 h incubation of SARS-CoV-2 and EGCG at 37 °C, the mixture was added to EGCG-exposed Vero cells, and the cells were incubated for an additional 2 h at 37 °C.…”

Molecular Mechanisms of Possible Action of Phenolic Compounds in COVID-19 Protection and Prevention

“…EGCG, previously mentioned as a potential M pro inhibitor, has also been shown to interact with viral S protein subunits, including S2 and RBD domains of both original and UK strain mutant virus, thus interrupting interaction with ACE2. EGCG binds to the RBD domain of the UK strain mutant slightly more effectively [115].…”