Design of HIV Coreceptor Derived Peptides That Inhibit Viral Entry at Submicromolar Concentrations.

ABSTRACT: HIV/AIDS continues to pose an enormous burden on global health. Current HIV therapeutics include inhibitors that target the enzymes HIV protease, reverse transcriptase, and integrase, along with viral entry inhibitors that block the initial steps of HIV infection by preventing membrane fusion or virus-coreceptor interactions. With regard to the latter, peptides derived from the HIV coreceptor CCR5 were previously shown to modestly inhibit entry of CCR5-tropic HIV strains, with a peptide containing residues 178-191 of the second extracellular loop (peptide 2C) showing the strongest inhibition. Here we use an iterative approach of amino acid scanning at positions shown to be important for binding the HIV envelope, and recombining favorable substitutions to greatly improve the potency of 2C.

SUBMITTER: Bobyk KD 

PROVIDER: S-EPMC7261408 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature