甘草香豆素抑制新型冠状病毒RNA聚合酶的实验研究及香豆素小分子的酶抑制活性预测OA

Objective To study the inhibitory activity of glycycoumarin against the main RNA polymerase of the novel corona-virus and to predict the inhibitory activity of coumarin small molecules against this target enzyme.Methods A cell-based novel coronavirus RNA polymerase catalytic reaction system was used to test the inhibitory activity of glycycoumarin against RNA poly-merase.Molecular docking technology was used to study the interaction mode of glycycoumarin and coumarin small molecules with amino acids at the active site of the main RNA polymerase of the novel coronavirus.Results In the RNA polymerase inhibi-tion assay,glycycoumarin showed inhibition rates were(29.68±4.06)％,(58.30±7.65)％and(86.85±5.78)％at concen-trations of 10,25,50 μmol/L,respectively.Glycycoumarin can enter the active site of RNA polymerase and interact with amino acids in the NTPs channel,releasing free energy of 7.6 kcal/mol during the binding process.Coumarin small molecules can bind to the active site of RNA polymerase and hinder the entry of normal substrate nucleotides.Conclusion Glycycoumarin has signifi-cant inhibitory activity against RNA polymerase.Coumarin small molecules can occupy the NTPs channel and inhibit the biologi-cal function of RNA polymerase.Structural modification based on the coumarin parent nucleus is a potential pathway for the de-velopment of anti-novel coronavirus drugs.