PDF(Pubmed)
Abstract：
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.
摘要：
3CL-Pro是SARS-CoV-2的主要蛋白酶(MPro)。它作为同源二聚体将大的多蛋白1ab转录物切割成病毒生长和复制所必需的蛋白质。3CL-Pro是研究最多的SARS-CoV-2蛋白之一，也是治疗的主要靶点。已经报道了一些候选药物，包括天然产品。这里,我们采用详细的计算方法来探索3CL-Pro蛋白的二聚化，我们制定了一个计算上下文来确定这个过程的潜在抑制剂。我们报道了福赛林（acacetin7-O-新橙皮苷），一种天然的黄酮类O-糖苷，其结构类似物是3CL-Pro二聚化的有效抑制剂，在体外抑制病毒空斑的形成。因此，我们为寻找对抗SARS-CoV-2和COVID-19的药物和膳食补充剂提供了新的基础。
