title: Structure-based identification of small molecule compounds targeting cell cyclophilin A with anti-HIV-1 activity.
abstract: Cyclophilin A acts as protein folding chaperones and intracellular transports in many cellular processes. Previous studies have shown that cyclophilin A can interact with HIV-1 (human immunodeficiency virus type 1) gag protein and enhance viral infectivity. Many cyclophilin A inhibitors such as cyclosporin A can inhibit HIV-1 replication in vitro. Here, we report a structure-based identification of novel non-peptidic cyclophilin A inhibitors as anti-HIV lead compounds. Following a computer-aided virtual screening and subsequent surface plasmon resonance (SPR) analysis, 12 low molecular weight cyclophilin A ligands were selected for further evaluation of their in vitro inhibition of peptidyl-prolyl cis-trans isomerase (PPIase) activity of cyclophilin A and HIV-1 replication. Five of these compounds (FD5, FD8, FD9, FD10 and FD12) exhibited inhibition against both PPIase activity and HIV-1 infection. These active compounds will be used as leads for structure and activity relationship (SAR) and optimization studies in order to design more effective anti-HIV-1 therapeutics, and as probes for investigating the effect of cyclophilins on HIV-1 replication.
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, People's Republic of China.
authors: Shuai
authors: S
authors: Chen
authors: Xuemei
authors: X
authors: Zhao
authors: Jinzhi
authors: J
authors: Tan
authors: Hong
authors: H
authors: Lu
authors: Zhi
authors: Z
authors: Qi
authors: Qiang
authors: Q
authors: Huang
authors: Xianzhuo
authors: X
authors: Zeng
authors: Mingjun
authors: M
authors: Zhang
authors: Shibo
authors: S
authors: Jiang
authors: Hualiang
authors: H
authors: Jiang
authors: Long
authors: L
authors: Yu
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D021984:Cyclophilin A / Q000037:antagonists & inhibitors*; D016572:Cyclosporine / Q000494:pharmacology; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors*; D020349:Surface Plasmon Resonance; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D016572:Cyclosporine; D021984:Cyclophilin A; D019696:Peptidylprolyl Isomerase