Molecules 2011, 16(5), 4264-4277; doi:10.3390/molecules16054264
Article

Mangiferin, an Anti-HIV-1 Agent Targeting Protease and Effective against Resistant Strains

Rui-Rui Wang 1,† , Yue-Dong Gao 2,3,† , Chun-Hui Ma 4 , Xing-Jie Zhang 1,3 , Cheng-Gang Huang 4,* email, Jing-Fei Huang 2,* email and Yong-Tang Zheng 1,* email
1 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 2 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 3 Graduate School of Chinese Academy of Sciences, Beijing 100039, China 4 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China † These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 25 February 2011; in revised form: 6 May 2011 / Accepted: 13 May 2011 / Published: 24 May 2011
(This article belongs to the Special Issue Antivirals)
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Abstract: The anti-HIV-1 activity of mangiferin was evaluated. Mangiferin can inhibit HIV-1ⅢB induced syncytium formation at non-cytotoxic concentrations, with a 50% effective concentration (EC50) at 16.90 μM and a therapeutic index (TI) above 140. Mangiferin also showed good activities in other laboratory-derived strains, clinically isolated strains and resistant HIV-1 strains. Mechanism studies revealed that mangiferin might inhibit the HIV-1 protease, but is still effective against HIV peptidic protease inhibitor resistant strains. A combination of docking and pharmacophore methods clarified possible binding modes of mangiferin in the HIV-1 protease. The pharmacophore model of mangiferin consists of two hydrogen bond donors and two hydrogen bond acceptors. Compared to pharmacophore features found in commercially available drugs, three pharmacophoric elements matched well and one novel pharmacophore element was observed. Moreover, molecular docking analysis demonstrated that the pharmacophoric elements play important roles in binding HIV-1 protease. Mangiferin is a novel nonpeptidic protease inhibitor with an original structure that represents an effective drug development strategy for combating drug resistance.
Keywords: mangiferin; HIV-1; protease; anti-HIV agents; drug resistance

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MDPI and ACS Style

Wang, R.-R.; Gao, Y.-D.; Ma, C.-H.; Zhang, X.-J.; Huang, C.-G.; Huang, J.-F.; Zheng, Y.-T. Mangiferin, an Anti-HIV-1 Agent Targeting Protease and Effective against Resistant Strains. Molecules 2011, 16, 4264-4277.

AMA Style

Wang R-R, Gao Y-D, Ma C-H, Zhang X-J, Huang C-G, Huang J-F, Zheng Y-T. Mangiferin, an Anti-HIV-1 Agent Targeting Protease and Effective against Resistant Strains. Molecules. 2011; 16(5):4264-4277.

Chicago/Turabian Style

Wang, Rui-Rui; Gao, Yue-Dong; Ma, Chun-Hui; Zhang, Xing-Jie; Huang, Cheng-Gang; Huang, Jing-Fei; Zheng, Yong-Tang. 2011. "Mangiferin, an Anti-HIV-1 Agent Targeting Protease and Effective against Resistant Strains." Molecules 16, no. 5: 4264-4277.

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