The mechanism of anticoronaviral action of CDK inhibitor flavopiridol

VernacularTitle:CDK抑制剂夫拉平度抗冠状病毒作用机制研究
Author: Li-dan WANG ; Sai-sai GUO ; Shan CEN
Publication Type:Research Article
Keywords: flavopiridol; CDK inhibitor; coronavirus; antiviral; RNA dependent RNA polymerase
From: Acta Pharmaceutica Sinica 2024;59(5):1280-1285
CountryChina
Language:Chinese
Abstract: Coronaviruses of the genus Coronavirus contain a variety of human pathogenic viruses, and the development of anti-coronavirus drugs is of great value. The development of antiviral drugs targeting host cells is not only helpful for the development of new antiviral strategies, but also for solving problems such as drug resistance due to viral mutations. Our preliminary study identified that cell cycle-dependent protein kinases (CDKs) involved in coronavirus replication, for which they would be potential anticoronaviral targets. In this study, we found that the broad-spectrum CDK inhibitor flavopiridol significantly inhibited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA dependent RNA polymerase (RdRp) activity. Further studies showed that flavopiridol suppressed the RNA synthesis efficiency of SARS-CoV-2 RdRp. In addition, flavopiridol effectively restricted the replication of human coronavirus OC43 (HCoV-OC43). Therefore, our study suggested that the CDK inhibitor flavopiridol may be a potential anticoronaviral drug.