A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B

Iyaniwura, Sarafa A.; Cassidy, Tyler; Ribeiro, Ruy M.; Perelson, Alan S.

doi:10.1371/journal.pcbi.1012322

A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B

Journal Article · Tue May 06 00:00:00 EDT 2025 · PLoS Computational Biology (Online)

DOI:https://doi.org/10.1371/journal.pcbi.1012322· OSTI ID:2570045

Iyaniwura, Sarafa A. ^[1]; ^[2]; ^[3]; ^[3]

Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Fred Hutchinson Cancer Center, Seattle, WA (United States)
University of Leeds (United Kingdom)
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

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’s 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.

View Accepted Manuscript (DOE)

Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); National Institutes of Health

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 2570045

Report Number(s):: LA-UR--25-23462; 10.1371/journal.pcbi.1012322; 1553-7358

Journal Information:: PLoS Computational Biology (Online), Journal Name: PLoS Computational Biology (Online) Journal Issue: 5 Vol. 21; ISSN 1553-7358

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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