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Dryad

Data from: Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure

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Mar 12, 2024 version files 263.09 GB

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.