Novel Dimeric Capsid Assembly Modulators as a Unique Class of Highly Potent Anti-HBV Agents
Approximately 250 million people are chronic HBV carriers and are at high risk of developing hepatitis, cirrhosis, and hepatocellular carcinoma. Several drugs are currently approved, but because they do not cure, lifelong therapies are the norm. HBV capsid assembly modulators (CAMs) have emerged as a promising option, as they lower several key markers of HBV replication. Novel dimeric structures (D-CAMs) were designed and evaluated. Their potency and mechanism of action were compared to those of monomeric D-CAMs, such as GLP-26. Among them, D-CAM-14 exhibited improved potency over GLP-26 and a unique effect on capsid morphology and kinetic assembly.
Authors
- Jéril Degrouard (ORCID: https://orcid.org/0000-0001-5024-4255)
- Lauren Matthews (ORCID: https://orcid.org/0000-0001-8843-5794)
- Franck Amblard (ORCID: https://orcid.org/0009-0002-6235-4050)
- Kalouna Kra (ORCID: https://orcid.org/0000-0001-7728-3262)
- Karen A. Kirby (ORCID: https://orcid.org/0000-0003-2468-4796)
- Laetitia Gargowitsch
- Dharmeshkumar Patel (ORCID: https://orcid.org/0000-0003-1601-256X)
- Alfred Jiang (ORCID: https://orcid.org/0009-0001-0517-9076)
- Guillaume Tresset (ORCID: https://orcid.org/0000-0002-3755-4109)
- Kiran Verma (ORCID: https://orcid.org/0000-0003-1871-2244)
- Leda Bassit (ORCID: https://orcid.org/0000-0001-9894-5587)
- Hugues de Rocquigny (ORCID: https://orcid.org/0000-0002-6585-8505)
- Eleftherios Michailidis (ORCID: https://orcid.org/0000-0002-9907-4346)
- Ana‐Andreea Arteni (ORCID: https://orcid.org/0000-0001-6462-905X)
- Virgile Rat (ORCID: https://orcid.org/0000-0002-6197-7523)
- Stefan G. Sarafianos (ORCID: https://orcid.org/0000-0002-5840-154X)
- David Durantel (ORCID: https://orcid.org/0000-0002-9226-3419)
- Raymond F. Schinazi (ORCID: https://orcid.org/0000-0002-6688-3614)
- Stéphane Bressanelli (ORCID: https://orcid.org/0000-0002-0921-6727)
- Zhe Chen (ORCID: https://orcid.org/0000-0002-3764-1587)
- Maedot Abate
- Mohammad Salman (ORCID: https://orcid.org/0009-0007-5677-9219)
- Antonis Athanasiadis (ORCID: https://orcid.org/0009-0000-6268-6683)
- S Ravichandran (ORCID: https://orcid.org/0009-0007-4960-3194)
- Georgios Dangas
- Julien Pronost
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Délégation Paris 5 (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Université Paris-Saclay (FR)
- Laboratoire de physique des Solides (FR)
- European Synchrotron Radiation Facility (FR)
- Hôpital Bretonneau (FR)
- Institut de Biologie Intégrative de la Cellule (FR)
- CEA Paris-Saclay (FR)
- Children's Healthcare of Atlanta (US)
- Centre International de Recherche en Infectiologie (FR)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1021/acs.jmedchem.5c01983
- Primary Topic
- Hepatitis B Virus Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00