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- Title
Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure.
- Authors
Faysal, K. M. Rifat; Walsh, James C.; Renner, Nadine; Márquez, Chantal L.; Shah, Vaibhav B.; Tuckwell, Andrew J.; Christie, Michelle P.; Parker, Michael W.; Turville, Stuart G.; Towers, Greg J.; James, Leo C.; Jacques, David A.; Böcking, Till
- 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.
- Subjects
GILEAD Sciences Inc.; HIV; ANTIRETROVIRAL agents; DRUG approval; ANTIVIRAL agents
- Publication
eLife, 2024, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.83605