{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:21:36Z","timestamp":1789611696223,"version":"build-2803163510"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and young children. In addition, RSV causes significant morbidity and mortality in hospitalized elderly and immunocompromised patients. Currently, only palivizumab, a monoclonal antibody against the RSV fusion (F) protein, and inhaled ribavirin are approved for the prophylactic and therapeutic treatment of RSV, respectively. Therefore, there is a clinical need for safe and effective therapeutic agents for RSV infections. GS-5806, discovered via chemical optimization of a hit from a high-throughput antiviral-screening campaign, selectively inhibits a diverse set of 75 RSV subtype A and B clinical isolates (mean 50% effective concentration [EC\n            <jats:sub>50<\/jats:sub>\n            ] = 0.43 nM). The compound maintained potency in primary human airway epithelial cells and exhibited low cytotoxicity in human cell lines and primary cell cultures (selectivity &gt; 23,000-fold). Time-of-addition and temperature shift studies demonstrated that GS-5806 does not block RSV attachment to cells but interferes with virus entry. Follow-up experiments showed potent inhibition of RSV F-mediated cell-to-cell fusion. RSV A and B variants resistant to GS-5806, due to mutations in F protein (RSV A, L138F or F140L\/N517I, and RSV B, F488L or F488S), were isolated and showed cross-resistance to other RSV fusion inhibitors, such as VP-14637, but remained fully sensitive to palivizumab and ribavirin. In summary, GS-5806 is a potent and selective RSV fusion inhibitor with antiviral activity against a diverse set of RSV clinical isolates. The compound is currently under clinical investigation for the treatment of RSV infection in pediatric, immunocompromised, and elderly patients.\n          <\/jats:p>","DOI":"10.1128\/aac.01497-15","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T04:43:50Z","timestamp":1450154630000},"page":"1264-1273","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":81,"title":["GS-5806 Inhibits a Broad Range of Respiratory Syncytial Virus Clinical Isolates by Blocking the Virus-Cell Fusion Process"],"prefix":"10.1128","volume":"60","author":[{"given":"Michel","family":"Perron","sequence":"first","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Stray","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April","family":"Kinkade","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy","family":"Theodore","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Lee","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sangi","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Jordan","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A.","family":"Piedra","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffery L.","family":"Toms","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Mackman","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Cihlar","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804877"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/01.inf.0000069765.43405.3b","article-title":"Risk factors for bronchiolitis-associated deaths among infants in the United States","volume":"22","author":"Holman RC","year":"2003","unstructured":"Holman RC, Shay DK, Curns AT, Lingappa JR, Anderson LJ. 2003. 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