{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:25:45Z","timestamp":1787199945143,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Respiratory syncytial virus (RSV) infection can result in a range of disease severity from mild upper respiratory tract symptoms to lower respiratory tract illness, with clinical manifestations dependent on age, co\u2010morbidities, and immune status. At present, there is no antiviral approved for adults with RSV disease, and only one treatment option with limited utilization is available for pediatric patients. While several RSV antiviral candidates have demonstrated virological efficacy in healthy adult challenge studies, to date they have subsequently failed to show efficacy in patients. Mechanistically understanding the translation of efficacy from preclinical to challenge to patient studies is essential in addressing this unmet medical need in children and adults with RSV disease. This work uses a quantitative systems pharmacology (QSP) approach to mathematically represent the underlying pathophysiology of RSV infection to simulate and predict the effects of investigational direct acting RSV antiviral therapeutics. We developed virtual populations that capture viral load dynamics in viral challenge studies, where the participants are healthy adult volunteers, upon treatment with the F\u2010protein inhibitor sisunatovir and the N\u2010protein inhibitor zelicapavir. Due to underlying differences in dynamics between key populations, we also developed a pediatric patient virtual population to match the results from the zelicapavir pediatric Phase 2 study. This work projects that for a minimum coverage &gt;\u20091\u00d7 free EC\n                    <jats:sub>90<\/jats:sub>\n                    at C\n                    <jats:sub>min<\/jats:sub>\n                    , a treatment window of 5 to 7\u2009days post\u2010symptom onset is feasible for observing virological efficacy in pediatric patients and may lead to potential success in a phase 3 pivotal RSV antiviral drug trial.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70308","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:21:56Z","timestamp":1785558116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Utilizing Virtual Clinical Trials to Inform Target Coverage That Drives\n                    <scp>RSV<\/scp>\n                    Antiviral Efficacy"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6240-9950","authenticated-orcid":false,"given":"J. Cody","family":"Herron","sequence":"first","affiliation":[{"name":"Pfizer Inc. Translational Clinical Sciences  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2148-9883","authenticated-orcid":false,"given":"Kathryn G.","family":"Link","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Translational Clinical Sciences  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Meacham","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Translational Clinical Sciences  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-5780","authenticated-orcid":false,"given":"Negar Niki","family":"Alami","sequence":"additional","affiliation":[{"name":"Pfizer Inc., R&amp;D  Pearl River New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7852-852X","authenticated-orcid":false,"given":"Daniel W.","family":"Brookes","sequence":"additional","affiliation":[{"name":"Pfizer Inc., R&amp;D, UK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2725-4279","authenticated-orcid":false,"given":"Elaine","family":"Thomas","sequence":"additional","affiliation":[{"name":"Pfizer Inc., R&amp;D, UK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Adams","sequence":"additional","affiliation":[{"name":"Pfizer Inc., R&amp;D  Pearl River New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sima S.","family":"Toussi","sequence":"additional","affiliation":[{"name":"Pfizer Inc., R&amp;D  Pearl River New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Franke","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Translational Clinical Sciences  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3003-0169","authenticated-orcid":false,"given":"Cynthia J.","family":"Musante","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Translational Clinical Sciences  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Najera","sequence":"additional","affiliation":[{"name":"Pfizer Inc., R&amp;D  Pearl River New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8038-9452","authenticated-orcid":false,"given":"Richard","family":"Allen","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Translational Clinical Sciences  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3624-9177","authenticated-orcid":false,"given":"Britton","family":"Boras","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Preclinical &amp; Translational Sciences  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1612"},{"key":"e_1_2_10_3_1","unstructured":"Division C.\u2010N.C.f.I.a.R.D.C.a.O.R.V \u201cClinical Overview of RSV \u201d(2025) https:\/\/www.cdc.gov\/rsv\/hcp\/clinical\u2010overview\/index.html."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1413456"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02152"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac404"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-976489"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit038"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/v5010211"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2313551"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.173"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-024-00625-x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12574"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009753"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-18244-2"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00285-019-01364-1"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.24506"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2108903"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01884-19"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/567589"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192645"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2018.07.029"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2018.07.027"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1413275"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1401184"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201002-0221OC"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy227"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir494"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy655"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0288271"},{"key":"e_1_2_10_31_1","unstructured":"Janssen Research & Development L. \u201cA Study of Rilematovir in Infants and Children and Subsequently in Neonates Hospitalized With Acute Respiratory Tract Infection due to Respiratory Syncytial Virus (RSV) (DAISY) \u201d(2025) https:\/\/clinicaltrials.gov\/study\/NCT04583280."},{"key":"e_1_2_10_32_1","unstructured":"hVIVO. 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