{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T18:30:23Z","timestamp":1784572223436,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Special Fund for the Construction of High-Level Universities in Guangdong Province","award":["88020032"],"award-info":[{"award-number":["88020032"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Influenza viruses persist as a significant global health challenge, with the emergence of drug-resistant strains limiting the effectiveness of current antiviral treatments. Inhibiting the early stages of viral replication is known to reduce virus-induced cytopathic effects; however, few therapeutics target these stages or the host factors supporting them, creating a critical gap in anti-influenza strategies development. This study aimed to address this gap by evaluating the antiviral potential of SB269970 HCl, a 5-HT7 receptor antagonist, against influenza viruses. We tested the efficacy of the compound using\n                    <jats:italic>in vitro<\/jats:italic>\n                    models (with multiple influenza strains) and an\n                    <jats:italic>in vivo<\/jats:italic>\n                    murine model of lethal influenza infection.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , SB269970 HCl effectively suppressed viral replication, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , it significantly improved survival rates and reduced the viral load in infected mice. Mechanistic experiments revealed that SB269970 HCl exerts its antiviral activity by blocking endocytosis of the influenza virus, a key step in the viral life cycle. Genetic knockdown of the 5-HT7 receptor inhibited viral entry, demonstrating the pivotal role of this receptor in facilitating viral internalization. These findings advance anti-influenza research by identifying the 5-HT7 receptor and its associated pathways as novel druggable targets. Unlike traditional antivirals, which are prone to resistance, SB269970 HCl targets host factors, offering a broad-spectrum strategy effective against diverse influenza strains, and establishing it as a promising candidate for further antiviral development.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1718860","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:51:56Z","timestamp":1774421516000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the 5-HT7 receptor to block influenza virus entry: mechanistic insights and therapeutic potential of SB269970 HCl"],"prefix":"10.3389","volume":"17","author":[{"given":"Yarou","family":"Gao","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingjian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Ke","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Lian","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lefang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xulin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/1743-422X-10-177","article-title":"Multiscale perspectives of virus entry via endocytosis","volume":"10","author":"Barrow","year":"2013","journal-title":"Virol. 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