Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure

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., The raw TIRF microscopy image stacks were collected using Micromanager (https://micro-manager.org/) and saved in TIFF format conforming to the OME standard (https://www.openmicroscopy.org/)., , # Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure

[https://doi.org/10.5061/dryad.18931zd49](https://doi.org/10.5061/dryad.18931zd49)

**Primary Depositor:** James Walsh
**Institution:** University of New South Wales
**Email:** [[e-mail]](mailto:[e-mail])
**ORCID:** 0000-0003-0447-2323
**Date:** The date of microscopy data acquisition is specified in the file name of each TIFF image stack, typically in the format YYYYMMDD.
**Location:** All data was collected at UNSW Sydney.
**Secondary Contact:** Till Boecking
**Email:** [[e-mail]](mailto:[e-mail])
**ORCID:** 0000-0003-1165-3122
**Funding:** National Health and Medical Research Council (APP1182212), National Health and Medical Research Council (APP1194263), Australian Research Council (DP160101874) and Australian Research Council (DP200102871), Wellcome Trust (214344/Z/18/Z).

This repository contains data collected for the pap...