基于计算机辅助药物设计的新冠病毒抑制剂的虚拟筛选及其活性验证  

Virtual Screening and Activity Verification of Novel Coronavirus Inhibitors Based on Computer-Aided Drug Design

作　　者：李震 王瑞 LI Zhen;WANG Rui(School of Pharmacy,Liaocheng University,Liaocheng 252059,China)

机构地区：[1]聊城大学药学院,山东聊城252059

出　　处：《聊城大学学报（自然科学版）》2022年第5期72-78,共7页Journal of Liaocheng University:Natural Science Edition

基　　金：国家自然科学基金项目(31401217);山东省抗体药物协同创新中心开放项目(CIC-AD1825)资助。

摘　　要：当下新冠病毒(SARS-CoV-2)已经在全球范围内造成了严重的健康和经济危机。新冠病毒通过S蛋白受体结合域(RBD)与宿主细胞的血管紧张素转化酶2(ACE2)结合,进而入侵细胞,这为开发相应的药物为阻断新冠病毒进入宿主细胞提供了一种有效的策略。利用Discovery Studio(DS)软件的ZDOCK和CDOCKER对接模块以及单点突变和多点突变来设计多肽阻断剂,并通过与RBD对接以及计算亲和力与hACE2,21~43肽进行比较,最后进行体外细胞实验验证多肽是否具有阻断新冠假病毒入侵细胞的能力。通过对接发现30~38肽在Zdock评分和ZRank评分上与野生型ACE2和21~43肽相似,将其设为初始肽段并通过突变进一步提高其亲和力,体外细胞实验验证多肽活性。通过DS软件设计的多肽长度较短且亲和力相当,具备阻断新冠病毒入侵细胞的能力,是潜在的新冠病毒的抑制剂。The new coronavirus(SARS-COV-2)has caused serious health and economic crisis in the world.The novel coronavirus invades cells by binding to the host cell’s ACE2 through the S protein receptor binding domain(RBD),this provides an effective strategy for the development of drugs to block the entry of coronaviruses into host cells.Peptide blockers were designed by using ZDOCK and CDOCKER docking modules of Discovery Studio(DS)software,single point mutation and multi-point mutation,and compared with RBD docking and calculation of affinity to hACE2,21~43 peptide,finally,in vitro cell experiments were performed to verify whether the peptides had the ability to block the invasion of new coronavirus into cells.The 30~38 peptide was found to be similar to wild type ACE2 and 21~43 peptide in Zdock score and ZRank score,and its affinity was further improved by mutation.The peptide designed by DS software is short in length and has similar affinity,which can block the invasion of new coronavirus and is a potential inhibitor of new coronavirus.

关 键 词：新冠病毒 DS 蛋白抑制剂 对接 突变 

分 类 号：R730[医药卫生—肿瘤]