Discovery of novel low-molecular-weight HIV-1 inhibitors interacting with cyclophilin A using in silico screening and biological evaluations |
| |
Authors: | Yu-Shi Tian Chris Verathamjamras Norihito Kawashita Kousuke Okamoto Teruo Yasunaga Kazuyoshi Ikuta Masanori Kameoka Tatsuya Takagi |
| |
Institution: | 1. Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan 2. Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Building 10, Department of Medical Sciences, Ministry of Public Health, Tiwanon Rd., Muang, Nonthaburi, 11000, Thailand 3. Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan 4. Department of Virology, Research Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
|
| |
Abstract: | Cyclophilin A has attracted attention recently as a new target of anti-human immunodeficiency virus type 1 (HIV-1) drugs. However, so far no drug against HIV-1 infection exhibiting this mechanism of action has been approved. To identify new potent candidates for inhibitors, we performed in silico screening of a commercial database of more than 1,300 drug-like compounds by using receptor-based docking studies. The candidates selected from docking studies were subsequently tested using biological assays to assess anti-HIV activities. As a result, two compounds were identified as the most active. Specifically, both exhibited anti-HIV activity against viral replication at a low concentration and relatively low cytotoxicity at the effective concentration inhibiting viral growth by 50 %. Further modification of these molecules may lead to the elucidation of potent inhibitors of HIV-1. Figure Docking poses of two compounds (23 and 12)?with anti-HIV activity |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|