Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor.

摘要: Inhibitors of the human immunodeficiency virus type 1 protease represent a promising class antiviral drugs for treatment AIDS, and several are now in clinical trials. Here, we report vitro selection viral variants with decreased sensitivity to C2-symmetric inhibitor (A-77003). We show that single amino acid substitution (Arg Gln or Lys) at position 8 results substantial decrease inhibitory activity drug on enzyme comparable increase resistance. These findings, when analyzed by using three-dimensional structure protease-drug complex, provide strategic guide future development inhibitors protease.