Inhibition of Human Immunodeficiency Virus Type 1 Entry by a Keggin Polyoxometalate

Wang, Xiaoli; Wang, Jiao; Zhang, Wenmei; Li, Boye; Zhu, Ying; Hu, Qin; Yang, Yishu; Zhang, Xiaoguang; Yan, Hong; Zeng, Yi

Human immunodeficiency virus type 1 (HIV-1) is the major cause of acquired immunodeficiency syndrome (AIDS). It has infected more than 36 million people worldwide by the end of 2015, according to the United Nations Joint Programme on HIV/AIDS (UNAIDS) reports. Significant success has been achieved in HIV-1 treatment since the introduction of highly active antiretroviral therapy (HAART) in the 1990s [1] . Current antiretroviral therapy, with three to four anti-HIV-1 drugs used in combination, targets multiple steps in the HIV-1 life cycle, including the viral reverse transcriptase, integrase, protease, viral entry, and fusion. Viral entry and fusion inhibitors are some of the most attractive agents in HIV-1 therapy [2] . In the last several decades, great progress has been made in the understanding of the mechanisms of HIV-1 entry into host cells. It involves the binding of viral glycoprotein gp120 to the cellular CD4 receptor, and subsequent reconfiguration of gp120 to allow the interaction of gp120 and a cellular coreceptor, i.e., CCR5 or CXCR4. The interaction was followed by additional conformational changes in the viral envelope, resulting in exposure of gp41 transmembrane protein and ultimately driving the fusion of the viral envelope with the host membrane [3] [4] [5] [6] [7] [8] . To date, the CCR5 antagonists maraviroc (MVC) and the fusion inhibitor targeting gp41, T20 (enfuvirtide) have been approved for clinical use, and many other inhibitors targeting various stages of viral entry are still in development [9, 10] .