Recent progress in the research of small molecule HIV-1 RNase H inhibitors.
Reverse transcription of human immunodeficiency virus type 1 (HIV-1) is a crucial step in the life cycle initiated by the viral-coded reverse transcriptase (RT), functioning as RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) and the ribonuclease H (RNase H). The RNase H functions to degrade the RNA strand of the RNA:DNA heteroduplex, which makes it an attractive target for rational anti-HIV-1 drug design and development. Although development of drugs targeting the DNA polymerase have been highly successful, the discovery of drugable inhibitors of HIV RNase H is still in its infancy and none of RNase H inhibitors has reached the clinical development stage currently. This review describes the recent progress in the HIV-1 RNase H inhibitors, focusing on their chemical feature, mechanism and the structure-activity relationship (SAR).
Lili
L
Cao
Weiguo
W
Song
Erik
E
De Clercq
Peng
P
Zhan
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, P.R.China. zhanpeng1982@sdu.edu.cn.
Xinyong
X
Liu
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D054309:Ribonuclease H, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D054309:Ribonuclease H, Human Immunodeficiency Virus