To explore the inhibitory activity of phloretin on the RNA polymerase of the novel coronavirus,and predict the target enzyme inhibitory activity of three small analogs molecules.
Molecular docking was employed to investigate the binding mode of phloretin with the active site of RNA polymerase. The inhibitory activity of phloretin on RNA polymerase was evaluated using a cell-based assay system for the catalytic reaction of the novel coronavirus RNA polymerase nsp7/nsp8/nsp12. Three small molecules from traditional Chinese medicine which was similar to the structure of rhizobin were selected to predict the inhibitory activity of the targeted enzyme,and the binding mode between them and the target enzyme activity site was studied by molecular docking method.
Phloretin exhibited favorable binding to the active site of RNA polymerase,occupying the NTPs channel and obstructing the entry of nucleotide substrates,thereby inhibiting RNA polymerase-directed nucleic acid replication. The results of pharmacological testing for the inhibition of RNA polymerase at the cellular level demonstrated that phloretin possesses significant inhibitory activity against the novel coronavirus RNA polymerase,albeit with weaker activity compared to remdesivir. However,phloretin exhibited lower cytotoxicity compared to remdesivir. It is predicted that phloretin analogs can also inhibit RNA polymerase and have pharmacological effects against novel coronavirus.
This study reveals the RNA polymerase inhibitory activity of phloretin,and predict that the small molecules of the rhizetin analogs also have RNA polymerase inhibitory activity,providing a potential reference 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 |