To study the inhibitory activity of glycycoumarin against the main RNA polymerase of the novel coronavirus and to predict the inhibitory activity of coumarin small molecules against this target enzyme.
A cell-based novel coronavirus RNA polymerase catalytic reaction system was used to test the inhibitory activity of glycycoumarin against RNA polymerase. 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.
In the RNA polymerase inhibition assay, glycycoumarin showed inhibition rates were (29.68±4.06)%, (58.30±7.65)% and (86.85±5.78)% at concentrations 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.
Glycycoumarin has significant inhibitory activity against RNA polymerase. Coumarin small molecules can occupy the NTPs channel and inhibit the biological function of RNA polymerase. Structural modification based on the coumarin parent nucleus is a potential pathway for the development of anti-novel coronavirus drugs.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |