Pharmacological intervention of HIV-1 maturation.
10.1016/j.apsb.2015.05.004
- Author:
Dan WANG
1
;
Wuxun LU
1
;
Feng LI
2
;
Author Information
1. Department of Biology and Microbiology, South Dakota State University, Brookings 57007, USA.
2. Department of Biology and Microbiology, South Dakota State University, Brookings 57007, USA
- Publication Type:Journal Article
- Keywords:
BMS, Bristol-Myers Squibb;
Bevirimat;
CA, capsid;
GSK, GlaxoSmithKline;
Gag processing;
Gag-drug interaction;
HIV, human immunodeficiency virus;
HIV-1 maturation inhibitors;
MA, matrix;
MI, maturation inhibitor;
PI, protease inhibitor;
PR, protease;
SIV, Simian immunodeficiency virus;
SP1, spacer protein 1
- From:
Acta Pharmaceutica Sinica B
2015;5(6):493-499
- CountryChina
- Language:English
-
Abstract:
Despite significant advances in antiretroviral therapy, increasing drug resistance and toxicities observed among many of the current approved human immunodeficiency virus (HIV) drugs indicate a need for discovery and development of potent and safe antivirals with a novel mechanism of action. Maturation inhibitors (MIs) represent one such new class of HIV therapies. MIs inhibit a late step in the HIV-1 Gag processing cascade, causing defective core condensation and the release of non-infectious virus particles from infected cells, thus blocking the spread of the infection to new cells. Clinical proof-of-concept for the MIs was established with betulinic acid derived bevirimat, the prototype HIV-1 MI. Despite the discontinuation of its further clinical development in 2010 due to a lack of uniform patient response caused by naturally occurring drug resistance Gag polymorphisms, several second-generation MIs with improved activity against viruses exhibiting Gag polymorphism mediated resistance have been recently discovered and are under clinical evaluation in HIV/AID patients. In this review, current understanding of HIV-1 MIs is described and recent progress made toward elucidating the mechanism of action, target identification and development of second-generation MIs is reviewed.
