摘要
新型冠状病毒仍在全球范围内传播,至今尚未有针对此病毒的特效药上市。为了找到对新型冠状病毒3-胰凝乳样蛋白酶(3CL pro)具有潜在抑制活性的分子,以3CL pro晶体复合物结构(PDB ID:6LU7)为受体,运用分子对接方法对内部构建的由天然氨基酸构成的二肽分子库进行虚拟筛选。结合对接打分、自由能计算、分子有效性及相互作用模式分析,挑选具有潜在抗病毒活性的小肽分子,并对潜在活性分子进行药代动力学性质及毒性预测。结果发现,3个小肽分子(氨基酸组成:YH,YN,TW)不仅与3CL pro结合口袋处His41,Cys145,Glu166,Gln189等关键氨基酸残基存在重要相互作用,而且无毒性且药代动力学性质合理,具备良好的成药性,可为抗新冠病毒药物研发提供先导化合物资源。
The SARS-CoV-2 is still spreading widely around the world,and there is no specific medicine for this virus on the market.This study is to discover a molecule with potential inhibitory activity against the SARS-CoV-23-chymotrypsin-like protease.Using the 3CL^(pro) crystal complex structure(PDB ID:6LU7)as the receptor,molecular docking was employed to virtual screen the internal constructed dipeptide compound library which was constructed by natural amino acids.Combining docking score,free energy calculation,molecular effectiveness and interaction mode analysis,the small peptide molecule which had potential antiviral activity was selected,and the pharmacokinetic properties and toxicity of the potential active molecules was predicted.Three small peptide molecules(amino acid constitution:YH,YN,TW)not only had important interactions with key amino acid residues in the 3CL^(pro) binding pocket,such as His41,Cys145,Glu166,Gln189,but also had reasonable pharmacokinetic properties,as well as without no toxicity.This study can provide leading compound resources for the development of anti SARS-CoV-2 drugs.
作者
陈姣
肖静
陈林
刘隆臻
CHEN Jiao;XIAO Jing;CHEN Lin;LIU Longzhen(Laboratory of Cell and Molecular Biology,Hospital of Integrated Chinese and Western Medicine Affiliated to Nanjing University of Traditional Chinese Medicine,Nanjing 210028,China;Dept.of Pharmacy,Ji’an Hospital of Shanghai Dongfang Hospital,Ji’an 343000,China;Dept.of Respiratory Medicine,Ji’an Hospital of Shanghai Dongfang Hospital,Ji’an 343000,China;College of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China;Dept.of Pharmacy,The Second Hospital of Zhuzhou City,Zhuzhou 412000,China)
出处
《江苏海洋大学学报（自然科学版）》
CAS
2021年第3期69-75,共7页
Journal of Jiangsu Ocean University:Natural Science Edition
基金
江西省卫生健康委员会科技计划项目(202140994)
吉安市指导性科技计划项目[2020](80)。
