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

Although the antiviral activity of POMs has been documented, the mode of antiviral action has remained elusive. Previous studies have demonstrated that POMs could block the HIV-1 reverse transcriptase (RT) or protease [19, 40] . Thus, we conducted the assay to test the inhibition on RT, protease, and integrase. PT-1 exhibited a certain degree of inhibition on RT and integrase, but not protease. We also observed that the RT inhibition percentage was not comparable to the HIV-1 inhibition percentage, indicating that the anti-HIV-1 activity was not fully mediated via inhibition of RT or integrase activity. To learn more about which steps of the HIV-1 cycle were targeted by PT-1, we conducted a time-drug-addition assay to have a thorough investigation of possible targets of the HIV-1 life-cycle. By adding PT-1 at different time points, we showed that PT-1 exhibited inhibition at a very early step of virus replication. Moreover, PT-1 specifically interacted with the HIV-1 envelope and not with VSV-G, thus the viral entry process might be the most likely antiviral target of PT-1.