{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T09:15:44Z","timestamp":1780823744435,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012322","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000}}],"reference-count":81,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI078881"],"award-info":[{"award-number":["R01-AI078881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-OD011095"],"award-info":[{"award-number":["R01-OD011095"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI116868"],"award-info":[{"award-number":["R01-AI116868"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound frequently occurs following treatment interruption. Consequently, functional cure rates of chronic HBV infection remain low and there is increased interest in a novel treatment modality, capsid assembly modulators (CAMs). Here, we develop a multiscale mathematical model of CAM treatment in chronic HBV infection. By fitting the model to participant data from a phase I trial of the first-generation CAM vebicorvir, we estimate the drug\u2019s dose-dependent effectiveness and identify the physiological mechanisms that drive the observed biphasic decline in HBV DNA and RNA, and mechanistic differences between HBeAg-positive and negative infection. Finally, we demonstrate analytically and numerically that the relative change of HBV RNA more accurately reflects the antiviral effectiveness of a CAM than the relative change in HBV DNA.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012322","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T13:58:35Z","timestamp":1746539915000},"page":"e1012322","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B"],"prefix":"10.1371","volume":"21","author":[{"given":"Sarafa A.","family":"Iyaniwura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0757-0017","authenticated-orcid":true,"given":"Tyler","family":"Cassidy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruy M.","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-0002","authenticated-orcid":true,"given":"Alan S.","family":"Perelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"pcbi.1012322.ref001","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.81070","article-title":"The forgotten people: Hepatitis B virus (HBV) infection as a priority for the inclusion health agenda","volume":"12","author":"E Martyn","year":"2023","journal-title":"Elife"},{"issue":"7734","key":"pcbi.1012322.ref002","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/d41586-018-07592-7","article-title":"The silent epidemic killing more people than HIV, malaria or TB","volume":"564","author":"I Graber-Stiehl","year":"2018","journal-title":"Nature"},{"key":"pcbi.1012322.ref003","unstructured":"WHO. 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