{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:42:28Z","timestamp":1792208548685,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"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":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:p>\n                    Dengue virus (DENV) infection is a significant global health threat. Mosnodenvir (JNJ\u201064281802) is a pan\u2010serotype small molecule antiviral blocking DENV replication. A Phase IIa study (NCT05048875) evaluated the antiviral activity, safety, and pharmacokinetics of mosnodenvir as prophylaxis against DENV\u20103 in a controlled human infection model (CHIM). A combined population pharmacokinetic (PopPK) and viral dynamic model (VDM) was developed to estimate the prophylactic effect of mosnodenvir and to inform dose selection. The PopPK model is a two\u2010compartment model based on plasma pharmacokinetic data from three Phase I studies and Cohort 1 of the Phase IIa study. Mosnodenvir exposure metrics were estimated for participants receiving high, medium, or low doses. A VDM with an immune response compartment adequately described DENV\u20103 RNA profiles for placebo participants and was subsequently extended by including a sigmoid\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    relationship with average mosnodenvir concentration at steady state (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>avg,ss<\/jats:sub>\n                    ) to capture the antiviral effect on virion production rate. Simulations supported daily and weekly mosnodenvir dosing regimens to further characterize the pharmacokinetic\/pharmacodynamic relationship in Cohort 2. Based on the complete Phase IIa study data, the basic reproductive number for DENV\u20103 in this CHIM was estimated at 21.7, and the typical\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>avg,ss<\/jats:sub>\n                    required to achieve complete virus eradication was estimated to be 1,410\u2009ng\/mL. In conclusion, the combined PopPK and VDM approach effectively informed dose selection and characterized the pharmacokinetic\u2010antiviral activity relationship, supporting the development of mosnodenvir as a prophylactic treatment for dengue infection.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70439","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:48:32Z","timestamp":1786337312000},"page":"1379-1388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Viral Dynamic Model\u2010Informed Dose Selection of Mosnodenvir Prophylaxis against\n                    <scp>DENV<\/scp>\n                    \u20103 in a Controlled Human Infection Model"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0526-5318","authenticated-orcid":false,"given":"Nele","family":"Goeyvaerts","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9400-5803","authenticated-orcid":false,"given":"Xavier Woot","family":"de Trixhe","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0959-3924","authenticated-orcid":false,"given":"Martine","family":"Neyens","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6857-2572","authenticated-orcid":false,"given":"Thomas N.","family":"Kakuda","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-9854","authenticated-orcid":false,"given":"Liesbeth","family":"Van Wesenbeeck","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0216-348X","authenticated-orcid":false,"given":"Annemie","family":"Buelens","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0943-5599","authenticated-orcid":false,"given":"Freya","family":"Rasschaert","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-2851","authenticated-orcid":false,"given":"Anna","family":"Durbin","sequence":"additional","affiliation":[{"name":"John Hopkins Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-5200","authenticated-orcid":false,"given":"Oliver","family":"Ackaert","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"Centers for Disease Control and Prevention.Dengue. About a dengue vaccine<https:\/\/www.cdc.gov\/dengue\/vaccine\/index.html> (2025). Accessed March 3 2025."},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00290"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11081328"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03771-y"},{"key":"e_1_2_10_5_1","unstructured":"Centers for Disease Control and Prevention.Storage & handling for dengue vaccine<https:\/\/www.cdc.gov\/vaccines\/vpd\/dengue\/hcp\/storage\u2010handling.html#:~:text=Storage%20and%20Handling%20for%20Dengue%20Vaccine \u2010Storage%20and%20Handling&text=Sanofi%2DPasteur%20will%20stop%20manufacturing specific%20to%20the%20dengue%20vaccine> (2024). 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