Virtual screening, identification, and biochemical characterization of novel inhibitors of the reverse transcriptase of human immunodeficiency virus type-1.
作者： Alon Herschhorn , Amnon Hizi
DOI: 10.1021/JM800473D
关键词: Virology 、 Molecular biology 、 DNA polymerase 、 Virus 、 Enzyme inhibitor 、 Enzyme 、 Reverse-transcriptase inhibitor 、 Chemistry 、 RNA-Directed DNA Polymerase 、 Reverse transcriptase 、 Chemical library
摘要: The reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) is a leading target in current antiretroviral therapy. Unfortunately, drug-resistant RT mutants evolve under the pressure these drugs, and therefore, new anti-RT inhibitors are constantly required for HIV-1/AIDS treatment. We virtually screened large chemical library compounds against two crystal structures HIV-1 to identify novel inhibitors. Top-scoring were tested experimentally; 71 inhibited RT-associated DNA polymerase, while several also pseudovirus infection cell-based assay. A combination substituents from structurally related single molecule improved inhibition efficacy. This compound strongly suppressed activity protecting lymphocytes infection. by this was reversible noncompetitive. another unrelated potent known mutant affected moderately HIV-2 polymerase. These may serve as promising anti-HIV lead compounds.
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