A Modified P1 Moiety Enhances In Vitro Antiviral Activity against Various Multidrug-Resistant HIV-1 Variants and In Vitro Central Nervous System Penetration Properties of a Novel Nonpeptidic Protease Inhibitor, GRL-10413.

ABSTRACT: We report here that GRL-10413, a novel nonpeptidic HIV-1 protease inhibitor (PI) containing a modified P1 moiety and a hydroxyethylamine sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC₅₀] of 0.00035 to 0.0018 μM), with minimal cytotoxicity (50% cytotoxic concentration [CC₅₀] = 35.7 μM). GRL-10413 blocked the infectivity and replication of HIV-1_NL4-3 variants selected by use of atazanavir, lopinavir, or amprenavir (APV) at concentrations of up to 5 μM (EC₅₀ = 0.0021 to 0.0023 μM). GRL-10413 also maintained its strong antiviral activity against multidrug-resistant clinical HIV-1 variants isolated from patients who no longer responded to various antiviral regimens

SUBMITTER: Amano M 

PROVIDER: S-EPMC5118983 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature