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

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.