新型冠状病毒相关靶点小分子抑制剂虚拟筛选

为确定治疗新型冠状病毒(SARS-CoV-2)感染的候选药物,开展了针对SARS-CoV-2的药物虚拟筛选研究。以SARS-CoV-2的刺突蛋白(S蛋白)和3CL蛋白酶(主蛋白酶)作为药物靶点,以美国食品药品监督管理局(FDA)批准上市的2 726个小分子药物作为候选,通过分子对接方法,筛选出了3种(阿巴瑞克(Abarelix)、西曲瑞克(Cetrorelix)、鞣酸(Tannic acid))与S蛋白具有较强结合能力的小分子药物,1种(戈舍瑞林(Goserelin))与3CL蛋白酶具有较好结合能力的小分子药物,它们理论上都具有抑制新型冠状病毒复制的效果。将靶向3CL蛋白酶的候选药物与辉瑞公司开发的药物Paxlovid进行比较,发现其作用位点均集中于3CL蛋白酶的第130-200位的残基周围,具有相似的结合位点与相互作用。此外也对候选药物的物理与化学性质及与基因相互作用进行了分析。本研究可为开发新型冠状病毒感染的治疗药物提供参考。

Virtual screening of small molecular inhibitors for SARS-CoV-2 related targets

In order to identify drug candidates for the treatment of SARS-CoV-2 infection, a virtual screening of drugs against SARS-CoV-2 was conducted. Using Spike protein (S protein) and 3CL protease (Main protease) as targets and 2 726 small molecular drugs approved by the US Food and Drug Administration (FDA) as candidates for molecular docking, we screened three small molecule drugs (Abarelix, Cetrorelix and Tannic acid) with strong binding effect with S protein and one small molecule drug(Goserelin) with strong binding effect with 3CL protease, all of which have the ability to inhibit SARS-CoV-2 replication process theoretically. Drug candidates targeting 3CL protease were compared with Paxlovid developed by Pfizer Inc and each drug had similar binding sites and interactions near the 130^th-200^th residues of 3CL protease. In addition, the physical and chemical properties of drug candidates and their interactions with genes were analyzed. This research may provide a reference for the development of drugs for treatment of SARS-CoV-2 infection.