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

The antiviral activity of POMs was first documented in 1970s, and they were later extensively studied in influenza, polioviruses, herpes simplex virus, etc. [13] [14] [15] . Especially, most POMs were found effective against HIV-1, HIV-2 and simian immunodeficiency virus (SIV) [21, 35] . HPA-23, known as antimonium tungstate, was one of the first-generation POM and the only one of all studied POMs so far that progressed to clinical trials. However, it caused adverse effects on the hepatic and renal functions [36] . POMs still suffer from the stigma of this failure, although new generations of POMs including Keggin structures, have been synthesized with less toxicity and greater efficacy, most studies have focused on cancer therapy [37, 38] , and very few studies have been conducted to investigate the anti-HIV potential in the past decade [39] . The mechanism of action has remained unclear. In the present work, we evaluated the potency and mechanism of action of a Keggin POM, PT-1 (K 6 HPTi 2 W 10 O 40 ) in preventing HIV-1 entry and replication. We demonstrated that PT-1 inhibited replication of multiple virus strains with IC 50 values in the nanomolar range. In addition to its remarkable high potency, it revealed low cytotoxicity and genotoxicity. The high therapeutic index (TI) makes PT-1 a good candidate for HIV-1 treatment.