Viability of a drug-resistant human immunodeficiency virus type 1 protease variant: structural insights for better antiviral therapy.

ABSTRACT: Under the selective pressure of protease inhibitor therapy, patients infected with human immunodeficiency virus (HIV) often develop drug-resistant HIV strains. One of the first drug-resistant mutations to arise in the protease, particularly in patients receiving indinavir or ritonavir treatment, is V82A, which compromises the binding of these and other inhibitors but allows the virus to remain viable. To probe this drug resistance, we solved the crystal structures of three natural substrates and two commercial drugs in complex with an inactive drug-resistant mutant (D25N/V82A) HIV-1 protease. Through structural analysis and comparison of the protein-ligand interactions, we found that Val82 interacts more closely with the drugs than with the natural substrate peptides. The V82A mutation com

SUBMITTER: Prabu-Jeyabalan M 

PROVIDER: S-EPMC140781 | biostudies-literature | 2003 Jan

REPOSITORIES: biostudies-literature