Document Type
Article
Publication Date
4-2011
Abstract
3-O-(3′,3′-Dimethylsuccinyl) betulinic acid (DSB), also known as PA-457, bevirimat (BVM), or MPC-4326, is a novel HIV-1 maturation inhibitor. Unlike protease inhibitors, BVM blocks the cleavage of the Gag capsid precursor (CA-SP1) to mature capsid (CA) protein, resulting in the release of immature, noninfectious viral particles. Despite the novel mechanism of action and initial progress made in small-scale clinical trials, further development of bevirimat has encountered unexpected challenges, because patients whose viruses contain genetic polymorphisms in the Gag SP1 (positions 6 to 8) protein do not generally respond well to BVM treatment. To better define the role of amino acid residues in the HIV-1 Gag SP1 protein that are involved in natural polymorphisms to confer resistance to the HIV-1 maturation inhibitor BVM, a series of Gag SP1 chimeras involving BVM-sensitive (subtype B) and BVM-resistant (subtype C) viruses was generated and characterized for sensitivity to BVM. We show that SP1 residue 7 of the Gag protein is a primary determinant of SP1 polymorphism-associated drug resistance to BVM.
Publication Title
Antimicrobial Agents and Chemotherapy
Volume
62
Issue
7
First Page
3324
Last Page
3329
Format
application/pdf
Language
en
DOI of Published Version
10.1128/AAC.01435-10
Publisher
American Society of Microbiology
Recommended Citation
Lu, Wuxun; Salzwedel, Karl; Wang, Dan; Chakravarty, Suvobrata; Freed, Eric O.; Wild, Carl T.; and Li, Feng, "A Single Polymorphism in HIV-1 Subtype C SP1 Is Sufficient To Confer Natural Resistance to the Maturation Inhibitor Bevirimat" (2011). Chemistry and Biochemistry Faculty Publications. 21.
https://openprairie.sdstate.edu/chem_pubs/21
Comments
Copyright © 2011, American Society for Microbiology