Title:Recent Advances in Computer-aided Antiviral Drug Design Targeting HIV-1 Integrase and Reverse Transcriptase Associated Ribonuclease H
Volume: 29
Issue: 10
关键词:
HIV-1整合酶、逆转录酶相关核糖核酸酶H、计算机辅助药物设计、耐药性预测、分子动力学、抗病毒药物。
摘要: Acquired immunodeficiency syndrome (AIDS) has been a chronic, life-threatening
disease for a long time. Though, a broad range of antiretroviral drug regimens is applicable
for the successful suppression of virus replication in human immunodeficiency virus type 1
(HIV-1) infected people. The mutation-induced drug resistance problems during the treatment
of AIDS forced people to continuously look for new antiviral agents. HIV-1 integrase (IN)
and reverse transcriptase associated ribonuclease (RT-RNase H), two pivotal enzymes in
HIV-1 replication progress, have gained popularity as druggable targets for designing novel
HIV-1 antiviral drugs. During the development of HIV-1 IN and/or RT-RNase H inhibitors,
computer-aided drug design (CADD), including homology modeling, pharmacophore, docking,
molecular dynamics (MD) simulation and binding free energy calculation, represent a
significant tool to accelerate the discovery of new drug candidates and reduce costs in antiviral
drug development. In this review, we summarized the recent advances in the design of single-
and dual-target inhibitors against HIV-1 IN or/and RT-RNase H as well as the prediction
of mutation-induced drug resistance based on computational methods. We highlighted the results
of the reported literatures and proposed some perspectives on the design of novel and
more effective antiviral drugs in the future.