%0 Journal Article
%T Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1.
%A Giammarino F
%A Sönnerborg A
%A Ceña-Diez R
%J Front Cell Infect Microbiol
%V 14
%N 0
%D 2024
%M 38915925
%F 6.073
%R 10.3389/fcimb.2024.1334126
%X <B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.