2. Academic Validation
  3. Structure-based Design of Novel Hepatitis B Virus Capsid Assembly Modulators

Structure-based Design of Novel Hepatitis B Virus Capsid Assembly Modulators

  • Bioorg Med Chem Lett. 2023 Sep 1;93:129412. doi: 10.1016/j.bmcl.2023.129412.
Elena Detta 1,  Angelica Corcuera 2,  Andreas Urban 2,  Thomas Goldner 3,  Susanne Bonsmann 2,  Florian Engel 2,  Marina M May 2,  Helmut Buschmann 2,  Mauro Fianchini 4,  Esther Alza 4,  Miquel A Pericàs 4,  Pavel A Pushkarev 5,  Anatolii O Varenyk 5,  Taras Y Yakovyuk 5,  Anton A Homon 5,  Pavlo A Sokoliuk 5,  Radomyr Smaliy 5,  Alastair Donald 2
Affiliations

Affiliations

  • 1 AiCuris Anti-infective Cures AG, Friedrich-Ebert-Str.475, 42117 Wuppertal, Germany; Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007 Tarragona, Spain.
  • 2 AiCuris Anti-infective Cures AG, Friedrich-Ebert-Str.475, 42117 Wuppertal, Germany.
  • 3 AiCuris Anti-infective Cures AG, Friedrich-Ebert-Str.475, 42117 Wuppertal, Germany. Electronic address: thomas.goldner@aicuris.com.
  • 4 Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007 Tarragona, Spain.
  • 5 Enamine Ltd, Chervonotkatska Street 78, 02094 Kyiv, Ukraine.
PMID: 37499987 DOI: 10.1016/j.bmcl.2023.129412
Abstract

Small-molecule capsid assembly modulators (CAMs) have been recently recognized as promising Antiviral agents for curing chronic hepatitis B virus (HBV) Infection. A target-based in silico screening study is described, aimed towards the discovery of novel HBV CAMs. Initial optimization of four weakly active screening hits was performed via focused library synthesis. Lead compound 42 and close analogues 56 and 57 exhibited in vitro potency in the sub- and micromolar range along with good physico-chemical properties and were further evaluated in molecular docking and mechanism of action studies.

Keywords

Capsid assembly; Hepatitis B; Molecular docking; Small molecules; Virtual screening.

Figures
Products