{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:05:32Z","timestamp":1789628732566,"version":"build-2803163510"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFD1800700"],"award-info":[{"award-number":["2021YFD1800700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172822"],"award-info":[{"award-number":["32172822"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["Z211100002121021"],"award-info":[{"award-number":["Z211100002121021"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The recent surge in global monkeypox (mpox) outbreaks highlights the critical need for developing antiviral agents targeting orthopoxvirus infections. Ibrutinib, a selective Bruton tyrosine kinase (BTK) inhibitor initially approved by the FDA in 2013 for treating chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), has emerged as a potential antiviral candidate based on a high-throughput screening for its efficacy against vaccinia virus (VACV). This study evaluated the antiviral capability of ibrutinib against VACV, mpox virus (MPXV), and lumpy skin disease virus (LSDV), demonstrating its strong antiviral activity against multiple poxviruses.\n              <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n              assays confirmed that ibrutinib significantly inhibited the replication of VACV, MPXV, and LSDV across multiple cell lines.\n              <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n              studies using VACV-infected BALB\/c mice revealed that ibrutinib treatment extended survival, mitigated weight loss and lesion formation, and reduced viral loads in infected mice. Mechanistic investigations indicated that ibrutinib inhibited viral early and late protein synthesis as well as DNA replication. Furthermore, BTK manipulation influenced viral replication, underscoring ibrutinib\u2019s antiviral action through a cellular target. Notably, BTK phosphorylation and nuclear translocation were observed during poxvirus infection, suggesting its role in viral replication. Overall, our findings suggest that ibrutinib is a promising candidate for treating poxvirus infections and that its cellular target, BTK, contributes to poxvirus replication.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                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\n                <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                and\n                <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                . 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.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00517-25","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:00:35Z","timestamp":1755694835000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Ibrutinib inhibits the replication of multiple poxviruses by targeting the Bruton tyrosine kinase"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8677-9675","authenticated-orcid":false,"given":"Kang","family":"Niu","sequence":"first","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University","place":["Beijing, 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