Synthesis and evaluation of highly potent HBV capsid assembly modulators (CAMs).
Antiviral
CAE
CAM
Drug
HBV capsid
Hepatitis
Ritonavir
Small molecules
Virus
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
received:
08
09
2023
revised:
10
10
2023
accepted:
16
10
2023
medline:
3
11
2023
pubmed:
24
10
2023
entrez:
23
10
2023
Statut:
ppublish
Résumé
Chronic hepatitis B virus (HBV) infection remains a major global health burden. It affects more than 290 million individuals worldwide and is responsible for approximately 900,000 deaths annually. Anti-HBV treatment with a nucleoside analog in combination with pegylated interferon are considered first-line therapy for patients with chronic HBV infection and liver inflammation. However, because cure rates are low, most patients will require lifetime treatment. HBV Capsid Assembly Modulators (CAMs) have emerged as a promising new class of compounds as they can affect levels of HBV covalently closed-circular DNA (cccDNA) associated with viral persistence. SAR studies around the core structure of lead HBV CAM GLP-26 (Fig. 1B) was performed and led to the discovery of non-toxic compound 10a displaying sub-nanomolar anti-HBV activity. Advanced toxicity and cellular pharmacology profiles of compounds 10a were also established and the results are discussed herein.
Identifiants
pubmed: 37871391
pii: S0045-2068(23)00584-9
doi: 10.1016/j.bioorg.2023.106923
pii:
doi:
Substances chimiques
Antiviral Agents
0
Capsid Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
106923Subventions
Organisme : NIAID NIH HHS
ID : R01 AI132833
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148740
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Drs. Schinazi, Amblard, Bassit, and Emory University, are entitled to equity and royalties related to anti-HBV products licensed to Aligos Therapeutics, Inc., being further evaluated in the research described in this paper. Emory University has reviewed and approved the terms of this arrangement per its conflict-of-interest policies.