tetano
Editor, Senior Moderator
Antiviral Res
. 2022 Mar 30;105296.
doi: 10.1016/j.antiviral.2022.105296. Online ahead of print.
The CDK1 inhibitor, Ro-3306, is a potential antiviral candidate against influenza virus infection
Lei Zhao[SUP] 1 [/SUP], Yunzheng Yan[SUP] 1 [/SUP], Qingsong Dai[SUP] 1 [/SUP], Zihao Wang[SUP] 1 [/SUP], Jiye Yin[SUP] 1 [/SUP], Yijie Xu[SUP] 1 [/SUP], Zhuang Wang[SUP] 1 [/SUP], Xiaojia Guo[SUP] 1 [/SUP], Wei Li[SUP] 1 [/SUP], Ruiyuan Cao[SUP] 2 [/SUP], Wu Zhong[SUP] 3 [/SUP]
Affiliations
Abstract
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.
Keywords: Antiviral; Cyclin-dependent kinases; Influenza virus; Mechanism; Ro-3306.
. 2022 Mar 30;105296.
doi: 10.1016/j.antiviral.2022.105296. Online ahead of print.
The CDK1 inhibitor, Ro-3306, is a potential antiviral candidate against influenza virus infection
Lei Zhao[SUP] 1 [/SUP], Yunzheng Yan[SUP] 1 [/SUP], Qingsong Dai[SUP] 1 [/SUP], Zihao Wang[SUP] 1 [/SUP], Jiye Yin[SUP] 1 [/SUP], Yijie Xu[SUP] 1 [/SUP], Zhuang Wang[SUP] 1 [/SUP], Xiaojia Guo[SUP] 1 [/SUP], Wei Li[SUP] 1 [/SUP], Ruiyuan Cao[SUP] 2 [/SUP], Wu Zhong[SUP] 3 [/SUP]
Affiliations
- PMID: 35367281
- DOI: 10.1016/j.antiviral.2022.105296
Abstract
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.
Keywords: Antiviral; Cyclin-dependent kinases; Influenza virus; Mechanism; Ro-3306.