2. Academic Validation
  3. Novel Dimeric Capsid Assembly Modulators as a Unique Class of Highly Potent Anti-HBV Agents

Novel Dimeric Capsid Assembly Modulators as a Unique Class of Highly Potent Anti-HBV Agents

  • J Med Chem. 2025 Nov 27;68(22):24196-24212. doi: 10.1021/acs.jmedchem.5c01983.
Franck Amblard 1,  Zhe Chen 1,  Kalouna Kra 2 3,  Dharmeshkumar Patel 1,  Leda Bassit 1,  Laetitia Gargowitsch 2,  Jéril Degrouard 2,  Virgile Rat 4,  Ana-Andreea Arteni 3,  Lauren Matthews 5,  Shreya M Ravichandran 1,  Alfred Jiang 1,  Antonis Athanasiadis 1,  Georgios Dangas 1,  Maedot Abate 1,  Guillaume Tresset 2,  Julien Pronost 6,  Mohammad Salman 1,  Kiran Verma 1,  Karen A Kirby 1,  Eleftherios Michailidis 1,  Hugues de Rocquigny 4,  David Durantel 6,  Stéphane Bressanelli 3,  Stefan G Sarafianos 1,  Raymond F Schinazi 1
Affiliations

Affiliations

  • 1 Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States.
  • 2 Université Paris-Saclay, CNRS, Laboratoire de Physique des Solides, 91405 Orsay, France.
  • 3 Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France.
  • 4 Morphogenèse et Antigénicité du VIH et des Virus des Hépatites, Inserm - U1259 MAVIVH, Hôpital Bretonneau, Tours 75018, France.
  • 5 European Synchrotron Radiation Facility, 38043 Grenoble, France.
  • 6 International Center for Research in Infectiology (CIRI), INSERM U1111, Université Claude Bernard Lyon, CNRS, UMR5308, ENS, Lyon 69365, France.
PMID: 41196228 DOI: 10.1021/acs.jmedchem.5c01983
Abstract

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-179265
    HBV Capsid Assembly Modulator
    HBV