{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:02:59Z","timestamp":1791396179655,"version":"4.3.3"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005612","name":"Shionogi & Co., Ltd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005612","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>S-337395 is a novel inhibitor of the respiratory syncytial virus (RSV) L-protein, and a potential oral antiviral against RSV. This phase 2a, randomized, double-blind, placebo-controlled, single-center, proof-of-concept trial conducted in the United Kingdom (April-October 2024) evaluated the efficacy, safety, and dose-response relationship of S-337395 against RSV infection in a human challenge model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Healthy adults aged 18\u201355 years meeting predefined eligibility criteria were inoculated with RSV-A Memphis 37b on Day 0. Nasal washes were collected for quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assessment twice daily on Days 2\u201312 and once on Day 13. Participants were randomized 5:13:13:13:13 to receive S-337395 (1, 10, 30, or 300 mg) or placebo, once daily for 5 days upon evidence of infection. Efficacy analyses were conducted in participants with confirmed RSV infection in intent-to-treat infected (ITT-I) set. Safety was assessed in all randomized participants. Dose-response was evaluated across a wide dose range (1\u2013300 mg).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 114 randomized participants, 60 comprised the ITT-I set. Covariate-adjusted mean viral load area under the curve (VL-AUC) was significantly lower in the 30- and 300-mg groups by qRT-PCR (64.87% and 88.94% reductions, respectively, both P &amp;lt; .05) and by viral culture assay (72.32% and 86.17% reductions, respectively, both P &amp;lt; .05). Total symptom score AUC was 78.15% lower in the 300-mg group (P &amp;lt; .05). S-337395 was well-tolerated without any safety concerns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>S-337395 significantly reduced viral load, viral titer, and symptoms, and was well-tolerated in this human challenge study.<\/jats:p>\n                    <jats:p>Clinical Trial Registration: ISRCTN24865912.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag367","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T11:26:26Z","timestamp":1781522786000},"page":"e652-e660","source":"Crossref","is-referenced-by-count":0,"title":["Phase 2a Randomized Placebo-Controlled Human Challenge Trial of the Respiratory Syncytial Virus L-Protein Inhibitor S-337395 for Respiratory Syncytial Virus Infection"],"prefix":"10.1093","volume":"83","author":[{"given":"Stuart","family":"Byrne","sequence":"first","affiliation":[{"name":"Drug Development and Regulatory Science Division, Shionogi & Co., Ltd. , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4968-2642","authenticated-orcid":false,"given":"Takamichi","family":"Baba","sequence":"additional","affiliation":[{"name":"Drug Development and Regulatory Science Division, Shionogi & Co., Ltd. , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9382-2382","authenticated-orcid":false,"given":"Nao","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Drug Development and Regulatory Science Division, Shionogi & Co., Ltd. , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3013-3975","authenticated-orcid":false,"given":"Atsuko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd. , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Nakano","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd. , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Dorrepaal","sequence":"additional","affiliation":[{"name":"Shionogi B.V. Medical Science Department, , London, England ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Londt","sequence":"additional","affiliation":[{"name":"hVIVO Services Limited Clinical Sciences Department, , London, England ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3744-4604","authenticated-orcid":false,"given":"Alex","family":"Mann","sequence":"additional","affiliation":[{"name":"hVIVO Services Limited Clinical Sciences Department, , London, England ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay","family":"Veselinski","sequence":"additional","affiliation":[{"name":"hVIVO Services Limited hSite Medical Operations, , London, England ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5853-9426","authenticated-orcid":false,"given":"Takeki","family":"Uehara","sequence":"additional","affiliation":[{"name":"Drug Development and Regulatory Science Division, Shionogi & Co., Ltd. , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"2026100713440983700_ciag367-B1","doi-asserted-by":"crossref","first-page":"103352","DOI":"10.1016\/j.eclinm.2025.103352","article-title":"Global outbreaks of respiratory syncytial virus infections from 1960 to 2025: a systematic review and meta-analysis","volume":"86","author":"Duan","year":"2025","journal-title":"eClinicalMedicine"},{"key":"2026100713440983700_ciag367-B2","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S0140-6736(24)01716-1","article-title":"Severe respiratory syncytial virus infection in 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