Pharmacomodulation of a ligand targeting the HBV capsid hydrophobic pocket

Autor: Mathilde Briday, François Hallé, Lauriane Lecoq, Sylvie Radix, Juliette Martin, Roland Montserret, Marie Dujardin, Marie-Laure Fogeron, Michael Nassal, Beat H. Meier, Thierry Lomberget, Anja Böckmann
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Chemical Science, 13 (30)
ISSN: 2041-6520
2041-6539
DOI: 10.3929/ethz-b-000559203
Popis: Hepatitis B virus (HBV) is a small enveloped retrotranscribing DNA virus and an important human pathogen. Its capsid-forming core protein (Cp) features a hydrophobic pocket proposed to be central notably in capsid envelopment. Indeed, mutations in and around this pocket can profoundly modulate, and even abolish, secretion of enveloped virions. We have recently shown that Triton X-100, a detergent used during Cp purification, binds to the hydrophobic pocket with micromolar affinity. We here performed pharmacomodulation of pocket binders through systematic modifications of the three distinct chemical moieties composing the Triton X-100 molecule. Using NMR and ITC, we found that the flat aromatic moiety is essential for binding, while the number of atoms of the aliphatic chain modulates binding affinity. The hydrophilic tail, in contrast, is highly tolerant to changes in both length and type. Our data provide essential information for designing a new class of HBV antivirals targeting capsid-envelope interactions.
Chemical Science, 13 (30)
ISSN:2041-6520
ISSN:2041-6539
Databáze: OpenAIRE