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

• Main Authors: Xiaoli Wang, Jiao Wang, Wenmei Zhang, Boye Li, Ying Zhu, Qin Hu, Yishu Yang, Xiaoguang Zhang, Hong Yan, Yi Zeng
• Format: Article
• Language: English
• Published: MDPI AG 2018-05-01
• Series: Viruses
• Subjects: human immunodeficiency virus type 1; Keggin polyoxometalate; entry inhibition; CD4; gp41 NHR
• Online Access: http://www.mdpi.com/1999-4915/10/5/265
• ISSN: 1999-4915

Here, we report the anti-human immunodeficiency virus (HIV) potency and underlying mechanisms of a Keggin polyoxometalate (PT-1, K6HPTi2W10O40). Our findings showed that PT-1 exhibited highly potent effects against a diverse group of HIV type 1 (HIV-1) strains and displayed low cytotoxicity and genotoxicity. The time-addition assay revealed that PT-1 acted at an early stage of infection, and these findings were supported by the observation that PT-1 had more potency against Env-pseudotyped virus than vesicular stomatitis virus glycoprotein (VSVG) pseudotyped virus. Surface plasmon resonance binding assays and flow cytometry analysis showed that PT-1 blocked the gp120 binding site in the CD4 receptor. Moreover, PT-1 bound directly to gp41 NHR (N36 peptide), thereby interrupting the core bundle formation of gp41. In conclusion, our data suggested that PT-1 may be developed as a new anti-HIV-1 agent through its effects on entry inhibition.