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

We further examined the ability of PT-1 to inhibit the viral protease, reverse transcriptase and integrase. Pepstatin A, nevirapine (NVP), and RAL were used as positive controls, respectively. PT-1 did not suppress protease activity ( Figure 5A ) but blocked reverse transcriptase activity ( Figure 5B ) and HIV-1 integrase 3 processing ( Figure 5C ) only at the highest concentration (17.6 µM). The maximum inhibition rates of reverse transcriptase and integrase 3 processing were approximately 70% and 60%, respectively. These data implied that in vitro reduction of reverse transcriptase and integrase activity was unlikely to be major mechanism of PT-1 induced HIV-1 inhibition at nanomolar concentrations. (A) Protease activity was assessed using a commercial kit, and pepstatin A was used as a positive control; (B) Reverse transcriptase activity was analyzed using a commercial kit with colorimetric assays; the percent inhibition was calculated as compared with the reverse transcriptase control. Nevirapine (NVP, 5 µM) was included as a positive control; (C) Integrase 3′-processing activity was analyzed by fluorescence resonance energy transfer. RAL was used as a positive control. All data were means ± standard deviations (SD) and were representative of three independent experiments.