Ibrutinib inhibits the replication of multiple poxviruses by targeting the Bruton tyrosine kinase

Abstract

Poxviruses are important zoonotic pathogens affecting human and animal health. The recent outbreak of monkeypox virus (MPXV) highlights the persistent threat posed by poxviruses to public health. In addition, lumpy skin disease virus (LSDV) causes economic impact by affecting the cattle industry. Currently, there are no effective drugs to combat LSD, which poses a major challenge to livestock health and productivity. Therefore, there is an urgent need to develop antiviral drugs against multiple poxviruses. Through high-throughput screening of antiviral drugs targeting vaccinia virus (VACV), we identified ibrutinib as a candidate antiviral drug. In our study, ibrutinib effectively inhibited the replication of MPXV, VACV, and LSDV in vitro and in vivo . Knockdown of Bruton tyrosine kinase (BTK), the cellular target of ibrutinib, significantly inhibited virus replication, while overexpression of BTK enhanced virus replication, which displays its role as a pro-viral effector. Overall, ibrutinib is a promising anti-poxvirus agent that can combat various poxviruses by targeting BTK.