Discovery of a Novel HIV-1 Integrase/p75 Interacting Inhibitor by Docking Screening, Biochemical Assay, and in Vitro Studies

Yan Wang, Huang Quan Lin, Ping Wang, Jian Shu Hu, Tsz Ming Ip, Liu Meng Yang, Yong Tang Zheng, David Chi-Cheong Wan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Protein-protein interaction between lens epithelium-derived growth factor (LEDGF/p75) and HIV-1 integrase becomes an attractive target for anti-HIV drug development. The blockade of this interaction by small molecules could potentially inhibit HIV-1 replication. These small molecules are termed as LEDGINs; and several newly identified LEDGINs have been reported to significantly reduce HIV-1 replication. Through this project, we have finished the docking screening of the Maybridge database against the p75 binding site of HIV-1 integrase using both DOCK and Autodock Vina software. Finally, we have successfully identified a novel scaffold LEDGINs inhibitor DW-D-5. Its antiviral activities and anticatalytic activity of HIV-1 integrase are similar to other LEDGINs under development. We demonstrated that the combination of DW-D-5 and FDA approved anti-HIV drugs resulted in additive inhibitory effects on HIV-1 replication, indicating that DW-D-5 could be an important component of combination pills for clinic use in HIV treatment.

Original languageEnglish (US)
Pages (from-to)2336-2343
Number of pages8
JournalJournal of Chemical Information and Modeling
Volume57
Issue number9
DOIs
StatePublished - Sep 25 2017

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