Research Article
Search for Low Molecular Weight Compounds that Inhibit Human Immunodeficiency Virus Type 1 Replication
| Chris Verathamjamras1#, Yu-Shi Tian2#, Norihito Kawashita2,3, Kousuke Okamoto2, Teruo Yasunaga3, Kazuyoshi Ikuta3, Kazushi Motomura1,3, Naokazu Takeda1,3, Tatsuya Takagi2,3* and Masanori Kameoka1,3,4* | ||
| 1Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Building 10, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi 11000, Thailand | ||
| 2Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan | ||
| 3Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan | ||
| 4Division of Infectious Diseases, Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142, Japan | ||
| #These authors equally contributed to this work. | ||
| Corresponding Authors : | Masanori Kameoka Division of Infectious Diseases, Department of International Health Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142, Japan Tel: +81 78 7964594 Fax: +81 78 7964594 E-mail: mkameoka@port.kobe-u.ac.jp |
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| Tatsuya Takagi Graduate School of Pharmaceutical Sciences Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan Tel: +81 6 68798244 Fax: +81 6 68798242 E-mail: satan@gen-info.osaka-u.ac.jp |
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| Received April 16, 2015; Accepted May 20, 2015; Published May 27, 2015 | ||
| Citation: Verathamjamras C, Tian Y, Kawashita N, Okamoto K, Yasunaga T, et al. (2015) Search for Low Molecular Weight Compounds that Inhibit Human Immunodeficiency Virus Type 1 Replication. J Infect Dis Ther 3:218. doi: 10.4172/2332-0877.1000218 | ||
| Copyright: © 2015 Verathamjamras C et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
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Abstract
Highly active antiretroviral (ARV) therapy has successfully reduced viral transmission, morbidity, and mortality associated with human immunodeficiency virus type 1 (HIV-1) disease; however, the emergence of drug-resistant viruses is a major obstacle associated with ARV . Therefore, the development of a new class of ARV drugs is urgently required. Cyclophilin A (CypA) is a host factor required for HIV-1 replication, and plays a role in viral replication by interacting with the HIV-1 capsid protein (CA). As such, it represents a potential target for novel ARV drugs. We here searched for low molecular weight compounds that inhibited HIV-1 replication by interfering with binding between CypA and HIV-1 CA. A total of 106 compounds were screened in an in silico docking study as candidates that were predicted to interact with the HIV-1 CA binding pocket of CypA. Biological tests were then conducted to evaluate the anti-HIV-1 activities as well as cytotoxicities of these test compounds, and 4 compounds that efficiently inhibited viral replication without exhibiting strong cytotoxicity were subsequently selected. The molecular mechanisms underlying the inhibition of HIV-1 replication by the 4 selected compounds have not been elucidated in the present study; however, we consider that these compounds will become the lead compounds for developing novel ARV drugs once more detailed studies are performed on the molecular mechanisms responsible for their anti-HIV-1 activities.
