Antiviral profile of hepatitis B virus capsid assembly modulator ALG-001075, the parent of pevifoscorvir sodium
- Author(s)
- Debing, Y; Vanrusselt, H; Liu, C; Verheyen, J; Degrauwe, L; Kum, DB; Sanchez, AA; Francisco, AC; Wanicek, E; Netter, HJ; Ramsland, PA; Leis, A; Shakeel, S; Deval, J; Welch, M; Serebryany, V; Stoycheva, A; Beigelman, L; Raboisson, P; Vendeville, S; Lin, TI; Blatt, LM; SMITH, DB; Symons, JA; Lecoq, L; Jekle, A;
- Journal Title
- Antiviral Research
- Publication Type
- Aug 17
- Abstract
- Chronic hepatitis B virus (HBV) infection remains an important unmet medical need with 240 million patients worldwide. The HBV capsid assembly process has emerged as a key target for more efficient antiviral intervention. Pevifoscorvir sodium (ALG-000184), an oral prodrug of the potent HBV capsid assembly modulator (CAM) ALG-001075 showed significant reductions in HBV DNA, HBV RNA and other viral antigens (HBsAg, HBcrAg and HBeAg) in Phase I clinical participants with chronic HBV infection. We aim to characterize the antiviral properties of ALG-001075. ALG-001075 is a highly potent CAM that inhibited HBV DNA production in cellular settings with EC(50) values below 1 nM and an EC(99.9) value of only 22 nM. ALG-001075 was shown to induce the formation of empty, but not aberrant viral particles as demonstrated by fluorescence quenching, electron microscopy, size-exclusion chromatography, immunofluorescent staining and NMR analysis, thereby classifying it as a CAM-E. Notably, solid-state NMR spectra of wild-type capsids in the presence of ALG-001075 revealed a characteristic CAM-E fingerprint at atomic resolution. ALG-001075 showed potent antiviral activity against HBV strains from genotypes A-J, nucleoside analogue-resistant virus strains and known CAM-resistance mutations, with the exception of T33N, T33P and V124G, which induced 6-to-28-fold loss in ALG-001075 activity. The in vivo efficacy of ALG-001075 was confirmed in adeno-associated virus-HBV mice, where ALG-001075 demonstrated up to 5 log(10) reduction in circulating HBV DNA levels. Because of its robust antiviral potency and favorable preclinical resistance profile, ALG-001075 was selected for further clinical development under the form of its prodrug pevifoscorvir sodium.
- Keywords
- antiviral therapy; capsid assembly modulator; chronic hepatitis B; hepatitis B virus
- Research Division(s)
- Structural Biology
- PubMed ID
- 42607766
- Publisher's Version
- https://doi.org/10.1016/j.antiviral.2026.106510
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-08-28 10:52:05
Last Modified: 2026-08-28 10:56:27