Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure.
Elife
; 132024 Feb 13.
Article
em En
| MEDLINE
| ID: mdl-38347802
ABSTRACT
The HIV-1 capsid has emerged as a tractable target for antiretroviral therapy. Lenacapavir, developed by Gilead Sciences, is the first capsid-targeting drug approved for medical use. Here, we investigate the effect of lenacapavir on HIV capsid stability and uncoating. We employ a single particle approach that simultaneously measures capsid content release and lattice persistence. We demonstrate that lenacapavir's potent antiviral activity is predominantly due to lethal hyperstabilisation of the capsid lattice and resultant loss of compartmentalisation. This study highlights that disrupting capsid metastability is a powerful strategy for the development of novel antivirals.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Fármacos Anti-HIV
Limite:
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Austrália