NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2020, Vol. 32 ›› Issue (12): 1981-1991. doi: 10.16333/j.1001-6880.2020.12.001

Special Issue: No.1

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Screening of RdRp inhibitors against SARS-CoV-2 based on prescription mining and pharmacophore

LI Jing1,2,WEI Bin-qi1,LI Ke-xin1,SU Xue-yan 1,3,ZHANG Zhi-feng1,3*   

  1. 1College of Pharmmacy,Southwest Minzu University;2State Key Laboratory of Biotherapy,Sichuan University,Chengdu 610041,China;
    3Sichuan Provincial Qiang-Yi Medicinal Resources Protection and Utilization Technology Engineering Laboratory,Chengdu 610225,China

  • Online:2020-12-28 Published:2020-12-24

Abstract:

In order to screen the potential RdRp inhibitors against SARS-CoV-2 based on prescription mining and pharmacophore.A comprehensive mining and screening of commonly used prescriptions was conducted and the use frequency of Chinese herbal medicines was calculated.The active components were screened by Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature mining.RdRp ligand-based pharmacophore model was set up by collecting published literature.The constituents from candidate active ingredients were screened for the potential RdRp inhibitors through matching with the best pharmacophore model.Molecular docking was used to evaluate the interactions between potential active compounds and SARS-CoV-2 RdRp protein.A total of 31 prescriptions including 92 kinds of herbs were collected.One thousand three hundred and eighty-four compounds were collected by TCMSP and literature mining.The optimized pharmacophore model,which was validated by test set,contained one hydrogen bond donor and two hydrogen bond acceptor.One hundred and four potential RdRp inhibitory constituents from candidate active ingredients were matched with the optimized pharmacophore model.The top 30 compounds with higher FitValue and lower binding free energy were selected for the analysis.Liquiritin apioside,iridin,liquiritin,forsythiaside,procyanidin B-5,3′-O-gallate,and saikosaponin C showed higher FitValue and lower binding energy,which were considered as potential active compounds.Flavonoids may be the potential active structure of RdRp inhibitors.A pharmacophore model was constructed to screen the potential RdRp inhibitors from commonly used prescriptions,in order to provide some ideas for screening the active components against SARS-CoV-2.

Key words: novel coronavirus pneumonia, SARS-CoV-2, RdRp inhibitors, prescription of traditional Chinese Medicine, pharmacophore, molecular docking

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