摘要
目的从理论上筛选出新型冠状病毒(SARS-CoV-2)的RNA依赖的RNA聚合酶(RdRp)抑制剂。方法依据SARS-CoV-2的RNA聚合酶与SARS聚合酶结构(6NUR)具有高度的同源性,以SARS的RNA聚合酶为模板构建SARS-CoV-2的RNA聚合酶的三维结构,利用分子对接软件Autodock Vina研究选中15个化合物与模型靶酶的相互作用,评估化合物对SARS-CoV-2的RNA聚合酶的抑制活性。结果研究发现,所选化合物均与靶酶的活性位点有一定相互作用,其中瑞德西韦活性形式、法匹拉韦活性形式、黄酮及异黄酮类化合物与靶酶的相互作用较强,以瑞德西韦活性形式与靶酶的结合能最低(为-7.9kal/mol),化合物1、2、8、13、14与酶的结合作用相对弱,提示对靶酶的抑制活性弱于瑞德西韦等,而化合物15没有酶抑制活性。结论通过虚拟筛选,得到了SARS-CoV-2 RNA聚合酶的一些抑制剂,其中的某些中药"活性成分"与目前临床上应用方剂的疗效具有较大的相关性,与清肺排毒汤等中医药治疗方案相互佐证。本研究为开发实施有效的抗新型冠状病毒治疗方案提供一定的理论参考,具体作用机制可进行进一步深入的研究验证。
Objective To screen RNA polymerase inhibitors for SARS-CoV-2 theoretically.Methods The RNA polymerase of SARS-CoV-2 shared high homology with SARS polymerase structure(6 NUR).In the present study,three-dimensional structure of SARS-CoV-2 RNA polymerase was constructed by using RNA polymerase as a template.Molecular docking software Autodock Vina was used to study the interaction of 15 selected compounds and model target enzyme.Results All other fourteen compounds had certain interactions with the active site of the target enzyme.Among them,the active form of Remdesivir or Favipiravir,flavonoids or isoflavones showed stronger interactions with target enzyme of SARS-CoV-2 RNA polymerase.The binding energy between the active form of Remdesivir and target enzyme was the lowest(-7.9 kal/mol).The interaction effect of compounds 1,2,8,13 or 14 and the target enzyme seemed to be weaker than that of Remdesivir,suggesting that the inhibitory activities of these compounds on the target enzyme were also weaker.The compound 15 had no inhibitory activity on the target enzyme.Conclusion Several RNA polymerase inhibitors for SARS-CoV-2 were obtained in silico screening.Among them,some compounds were the active components of traditional Chinese medicine.These results showed a great correlation with the therapeutic effect of current prescriptions strategy,supporting that the treatment of traditional Chinese medicine,such as Qingfei Paidu Decoction,would be effective.The present study provided some theoretical evidence for the development of effective treatment strategy for SARS-CoV-2 infection.The action mechanism of the above drugs should be further studied and identified.
作者
苏彦雷
段绪红
许文成
赵玲
关世奎
SU Yanlei;DUAN Xuhong;XU Wencheng;ZHAO Ling;GUAN Shikui(Department of Pharmacy,The 980th Hospital of The Logistics Support Force of The Chinese Peoples Liberation Army,Shjazhuang 050082,Hebei,China;Hebei Province Academy of Chinese Medicine Sciences,Shijiazhuang 050030,Hebei,China;Department of Pharmacy,Hubei Provinvial Hospital of Traditional Chinese Medicine,Wuhan 430064,Hubei,China;School of Biology and Pharmaceutical Engineering,W uhan Polytechnic University,Wuhan 430023,Hubei,China;Beidaihe Sanatorinm of the Joint Logistics Support Force of the Chinese Peoples Liberation Army,Beidaihe 066100,Hebei,China)
出处
《中华中医药学刊》
CAS
北大核心
2020年第5期7-13,I0011,I0012,共9页
Chinese Archives of Traditional Chinese Medicine
