The CDK1 inhibitor, Ro-3306, is a potential antiviral candidate against influenza virus infection.

Many viruses use the host cell division cycle to facilitate replication. Cyclin-dependent kinases (CDKs) are a group of serine/threonine kinases that play a central role in regulating cell cycle progression. However, the prospect of using CDKs for anti-influenza virus treatment remains to be elucidated. We conducted this study to investigate the potential of the CDK1 inhibitor Ro-3306 in preventing influenza virus infection and to elucidate the underlying mechanism. We showed that Ro-3306, a CDK1 inhibitor, exerts anti-influenza activity both in vitro and in vivo. Proof-of-concept studies revealed that knockdown of host CDK1 might affect the splicing of M2 viral mRNA, leading to the restriction of viral replication. Moreover, Ro-3306 directly bound to viral PB2 protein and inhibited viral RNA replication. Transcriptome analysis further revealed that Ro-3306 treatment inhibited the expression of MAPK-regulated genes, which might also contribute to the antiviral activity of Ro-3306. This study highlighted the multifunctional role of Ro-3306 as a novel anti-influenza virus agent.