Faysal, KM Rifat;
Walsh, James C;
Renner, Nadine;
Márquez, Chantal L;
Shah, Vaibhav B;
Tuckwell, Andrew J;
Christie, Michelle P;
... Böcking, Till; + view all
(2024)
Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure.
Elife
, 13
, Article e83605. 10.7554/eLife.83605.
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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.
Type: | Article |
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Title: | Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure |
Location: | England |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.7554/eLife.83605 |
Publisher version: | http://dx.doi.org/10.7554/elife.83605 |
Language: | English |
Additional information: | © 2024, Faysal, Walsh et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
Keywords: | HIV-1, capsid, drug mechanism of action, infectious disease, microbiology, molecular biophysics, none, structural biology |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
URI: | https://discovery.ucl.ac.uk/id/eprint/10187888 |
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