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Nucleocapsid Annealing-Mediated Electrophoresis NAME Assay Allows the Rapid Identification of HIV-1 Nucleocapsid Inhibitors
Published on: January 19, 2015
Rotten to the core: antivirals targeting the HIV-1 capsid core
William M McFadden1, Alexa A Snyder1, Karen A Kirby1,2
1Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Abstract:
The capsid core of HIV-1 is a large macromolecular assembly that surrounds the viral genome and is an essential component of the infectious virus. In addition to its multiple roles throughout the viral life cycle, the capsid interacts with multiple host factors. Owing to its indispensable nature, the HIV-1 capsid has been the target of numerous antiretrovirals, though most capsid-targeting molecules have not had clinical success until recently. Lenacapavir, a long-acting drug that targets the HIV-1 capsid, is currently undergoing phase 2/3 clinical trials, making it the most successful capsid inhibitor to-date. In this review, we detail the role of the HIV-1 capsid protein in the virus life cycle, categorize antiviral compounds based on their targeting of five sites within the HIV-1 capsid, and discuss their molecular interactions and mechanisms of action. The diverse range of inhibition mechanisms provides insight into possible new strategies for designing novel HIV-1 drugs and furthers our understanding of HIV-1 biology.
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