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Highly resistant HIV-1 proteases and strategies for their inhibition.

Authors :
Weber IT
Kneller DW
Wong-Sam A
Source :
Future medicinal chemistry [Future Med Chem] 2015; Vol. 7 (8), pp. 1023-38.
Publication Year :
2015

Abstract

The virally encoded protease is an important drug target for AIDS therapy. Despite the potency of the current drugs, infections with resistant viral strains limit the long-term effectiveness of therapy. Highly resistant variants of HIV protease from clinical isolates have different combinations of about 20 mutations and several orders of magnitude worse binding affinity for clinical inhibitors. Strategies are being explored to inhibit these highly resistant mutants. The existing inhibitors can be modified by introducing groups with the potential to form new interactions with conserved protease residues, and the flexible flaps. Alternative strategies are discussed, including designing inhibitors to bind to the open conformation of the protease dimer, and inhibition of the protease-catalyzed processing of the Gag-Pol precursor.

Details

Language :
English
ISSN :
1756-8927
Volume :
7
Issue :
8
Database :
MEDLINE
Journal :
Future medicinal chemistry
Publication Type :
Academic Journal
Accession number :
26062399
Full Text :
https://doi.org/10.4155/fmc.15.44