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Article Abstract
Targeting the capsid protein of the hepatitis B virus (HBV) has emerged as a promising strategy for developing new antiviral therapies. In this study, we report the discovery of a novel series of pyrrole oxo-carboxamide compounds as HBV capsid assembly modulators (CAMs) that block viral replication. Through a process of focused structure-activity relationship (SAR) optimization, we identified compound (VNRX-9945), which exhibited excellent and broad antiviral activity against multiple HBV genotypes in vitro, along with favorable pharmacokinetic profiles across multiple species. Additionally, demonstrated robust efficacy in the adeno-associated virus mouse model of HBV (AAV-HBV) infection. This compound has advanced into Phase 1 clinical trials to evaluate its safety and pharmacokinetics in healthy volunteers, to enable treatment of chronic HBV infections.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257411 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.5c00315 | DOI Listing |
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