Naturally occurring dipeptide from elite controllers with dual anti-HIV-1 mechanism.

We have reported enhanced levels of a dipeptide, WG-am, among elite controllers, patients who spontaneously control their HIV-1 infection. The aim of the present work was to evaluate its anti-HIV-1 activity and mechanism of action. Our data suggest that WG-am binds to the CD4 binding pocket of HIV-1 gp120 and blocks its binding to the host cell receptors. Additionally, our time course assay showed that WG-am inhibited HIV-1 also at 4-6h post-infection, suggesting a second antiviral mechanism. Drug sensitivity assays under acidic wash conditions confirmed the ability of WG-am to internalize into the host cell in an HIV independent manner. Proteomic studies showed a clustering of all samples treated with WG-am independent on the number of doses or presence or absence of HIV-1. Differentially expressed proteins due to the WG-am treatment indicated an effect on HIV-1 reverse transcription, which was confirmed by RT-PCR. Naturally occurring in HIV-1 elite controllers, WG-am stands out as a new kind of antiviral compound with two independent inhibitory mechanisms of action on HIV-1 replication. WG-am halts HIV-1 entry to the host cell by binding to HIV-1 gp120, thereby blocking the binding of HIV-1 to the host cell. It has also a post-entry, but pre-integration antiviral effect related to inhibition of RT-activity.