{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:27:29Z","timestamp":1792787249418,"version":"4.5.0"},"reference-count":59,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Guizhou Provincial Respiratory Critical Disease Clinical Research and Prevention and Treatment Talent Base Project","award":["[2020]8"],"award-info":[{"award-number":["[2020]8"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360001"],"award-info":[{"award-number":["82360001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Commission of Guizhou Provincial","award":["gzwkj2023-17"],"award-info":[{"award-number":["gzwkj2023-17"]}],"id":[{"id":"https:\/\/ror.org\/027yzwq33","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018555","name":"Science and Technology Project of Guizhou Province","doi-asserted-by":"publisher","award":["ZK[2022]581"],"award-info":[{"award-number":["ZK[2022]581"]}],"id":[{"id":"10.13039\/501100018555","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Bureau of Zunyi","award":["Zun City Kehe HZ character (2023) No. 14"],"award-info":[{"award-number":["Zun City Kehe HZ character (2023) No. 14"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections in infants, older adults, and immunocompromised individuals, but therapeutic options for active infection remain limited. Interleukin-6 (IL-6) contributes to RSV replication and RSV-induced inflammation, and the IKK\u03b2\/NF-\u03baB pathway is a major regulator of IL-6 expression. Bardoxolone methyl (BXM) was identified by network medicine as a potential anti-RSV compound, with molecular docking suggesting interactions with the IKK\u03b2\/NF-\u03baB pathway. We investigated whether BXM inhibits RSV infection through modulation of the IKK\u03b2\/NF-\u03baB\/IL-6 axis in RSV-infected BEAS-2B cells and BALB\/c mice. RSV infection increased IL-6 expression and activated IKK\u03b2\/NF-\u03baB signaling, whereas IL-6 knockdown reduced viral replication and inflammatory mediator expression. BXM significantly suppressed RSV replication, as shown by RT-qPCR, TCID\u2085\u2080, plaque reduction assays, and Western blotting, and decreased IL-6 expression\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Mechanistically, BXM attenuated RSV-induced phosphorylation of IKK\u03b2 and NF-\u03baB. The IKK\u03b2 inhibitor TPCA-1 produced similar inhibitory effects, whereas recombinant human IL-6 add-back partially restored inflammatory mediator expression in BXM-treated RSV-infected cells. In mice, BXM reduced lung viral titers, RSV-F expression, IL-6 expression, IKK\u03b2\/NF-\u03baB activation, and RSV-induced lung injury. These findings suggest that BXM suppresses RSV replication and inflammation, at least in part, by modulating the IKK\u03b2\/NF-\u03baB\/IL-6 axis, supporting its potential as a therapeutic candidate for RSV infection.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Respiratory syncytial virus (RSV) is a major cause of respiratory illness, especially in infants, older adults, and people with weakened immune systems. Although preventive strategies are available for some high-risk groups, treatment options for active RSV infection remain limited. This study identifies bardoxolone methyl (BXM) as a potential anti-RSV compound and shows that it can reduce both viral replication and virus-induced inflammation in cell and mouse models. Importantly, our findings suggest that BXM acts, at least in part, by reducing IL-6-related inflammatory signaling, which is closely associated with RSV disease severity. These results provide experimental evidence supporting BXM as a promising candidate for further development against RSV infection and offer insight into a potential host-targeted therapeutic strategy.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03825-25","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:01:58Z","timestamp":1789736518000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Bardoxolone methyl exerts an inhibitory effect on respiratory syncytial virus infection by downregulating IL-6 via the IKK\u03b2\/NF-\u03baB signaling 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