# Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1

## TL;DR

A naturally occurring dipeptide, Tryptophylglycine (WG), shows strong synergy with antiretrovirals against drug-resistant HIV-1 strains.

## Contribution

WG demonstrates synergistic antiviral activity with multiple antiretrovirals against multi-drug resistant HIV-1 isolates.

## Key findings

- WG-am showed strong synergism with raltegravir, tenofovir, efavirenz, and darunavir against drug-resistant HIV-1 isolates.
- Combination of WG-am with antiretrovirals inhibited all drug-resistant isolates with over 95% reduction.
- Highest selectivity indexes were observed in isolates resistant to integrase strand transfer inhibitors.

## Abstract

The naturally occurring dipeptide Tryptophylglycine (WG) is enhanced in human immunodeficiency virus (HIV-1) infected Elite Controllers (EC). We have shown that this dipeptide has an anti-HIV-1 effect and evaluated now its synergistic antiretroviral activity, in combination with current antiretrovirals against multi-drug resistant HIV-1 isolates.

Drug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay’s Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism.

WG-am had a moderate/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: <0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50/ED50) were in INSTI-resistant isolates.

Our data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV-1 compounds.