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.

在寻找抗 SARS-CoV-2 药物的过程中，人们非常关注安全且广泛使用的天然化合物。绿茶成分表没食子儿茶素 3 没食子酸酯 (EGCG) 特别有前途，因为据报道它可以在体外抑制病毒复制和病毒进入. 然而，需要其主要活动的确凿证据。我们在两个独立的系列实验中测试了 EGCG 对从 COVID-19 患者分离出的天然病毒的影响，这些实验使用 VERO 细胞和每个系列中的两种不同治疗方案。结果证实了 EGCG 的适度细胞毒性及其显着的抗病毒活性。旨在预防感染的预孵育计划已被证明特别有益。我们通过详细研究 EGCG 与病毒 S 蛋白亚基（包括 S2、RBD 和携带 N501Y 突变的 RBD 突变体）的相互作用来补充这一发现。分子建模实验揭示了 RBD-ACE2 复合物中 N501Y 特异性堆积相互作用，并提供了对 EGCG 干扰复合物形成的深入了解。一起，