Tsai Ming-Shao, Yang Yao-Hsu, Lin Yu-Shih, Chang Geng-He, Hsu Cheng-Ming, Yeh Reming-Albert, Shu Li-Hsin, Cheng Yu-Ching, Liu Hung-Te, Wu Yu-Huei, Wu Yu-Heng, Shen Rou-Chen, Wu Ching-Yuan
Department of Otolaryngology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Faculty of Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; School of Chinese medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Biomed Pharmacother. 2021 Oct;142:112011. doi: 10.1016/j.biopha.2021.112011. Epub 2021 Aug 5.
Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike protein and subsequently increase the infectivity of the beta variant. The L452R mutation in the epsilon variant (the B.1.427/B.1.429 variants) also reduced neutralizing activity of monoclonal antibodies. In this study, we discovered that 300 μg/mL GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and wild-type (Wuhan type) RBD spike protein. GB-2 can inhibit the binding between ACE2 and RBD with K417N-E484K-N501Y mutation in a dose-dependent manner. GB-2 inhibited the binding between ACE2 and the RBD with a single mutation (K417N or N501Y or L452R) except the E484K mutation. In the compositions of GB-2, glycyrrhiza uralensis Fisch. ex DC., theaflavin and (+)-catechin cannot inhibit the binding between ACE2 and wild-type RBD spike protein. Theaflavin 3-gallate can inhibit the binding between ACE2 and wild-type RBD spike protein. Our results suggest that GB-2 could be a potential candidate for the prophylaxis of some SARS-CoV-2 variants infection in the further clinical study because of its inhibition of binding between ACE2 and RBD with K417N-E484K-N501Y mutations or L452R mutation.
自中国武汉爆发2019冠状病毒病以来，向世界卫生组织报告的该疾病确诊病例已超过1.5亿例。β变异株（B.1.351谱系）是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的突变谱系，由于刺突蛋白中的多个突变，其传播性和对中和抗体的抗性有所增加。受体结合域（RBD）区域中的N501Y、K417N和E484K可能会诱导刺突蛋白的构象变化，进而增加β变异株的传染性。ε变异株（B.1.427/B.1.429变异株）中的L452R突变也降低了单克隆抗体的中和活性。在本研究中，我们发现来自嘉义朴子配天宫天上圣母的300μg/mL GB-2可抑制血管紧张素转换酶2（ACE2）与野生型（武汉型）RBD刺突蛋白之间的结合。GB-2能以剂量依赖的方式抑制ACE2与具有K417N-E484K-N501Y突变的RBD之间的结合。除E484K突变外，GB-2抑制ACE2与具有单个突变（K417N或N501Y或L452R）的RBD之间的结合。在GB-2的成分中，甘草、茶黄素和（+）-儿茶素不能抑制ACE2与野生型RBD刺突蛋白之间的结合。茶黄素-3-没食子酸酯可抑制ACE2与野生型RBD刺突蛋白之间的结合。我们的结果表明，由于GB-2能抑制ACE2与具有K417N-E484K-N501Y突变或L452R突变的RBD之间的结合，在进一步的临床研究中，它可能是预防某些SARS-CoV-2变异株感染的潜在候选药物。
