CDK抑制剂夫拉平度抗冠状病毒作用机制研究

The mechanism of anticoronaviral action of CDK inhibitor flavopiridol

冠状病毒属冠状病毒包含多种人类致病病毒,抗冠状病毒药物研发具有重要价值。开发靶向宿主细胞的抗病毒药物不仅有助于发展新的抗病毒策略,同时有利于解决病毒突变而带来的耐药性等问题。本课题组前期研究发现,细胞周期依赖性蛋白激酶(cell cycle-dependent protein kinases,CDKs)参与冠状病毒的复制,成为潜在的抗病毒靶点。本研究发现广谱CDK抑制剂夫拉平度显著抑制严重急性呼吸系统综合征冠状病毒2 (severe acute respiratory syndrome coronavirus 2,SARS-CoV-2) RNA依赖性RNA聚合酶(RNA dependent RNA polymerase,RdRp)活性。进一步研究表明,夫拉平度抑制SARS-CoV-2 RdRp的RNA合成效率。此外,夫拉平度能够有效抑制人类冠状病毒OC43 (human coronavirus OC43,HCoV-OC43)的复制。本研究表明,CDK抑制剂夫拉平度可能是潜在的抗冠状病毒药物。

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.