Small molecule inhibitors of HIVgp41 N-heptad repeat trimer formation.

ABSTRACT: Identification of mechanistically novel anti-HIV fusion inhibitors was accomplished using a computer-aided structure-based design approach with the goal of blocking the formation of the N-heptad repeat (NHR) trimer of the viral protein gp41. A virtual screening strategy that included per-residue interaction patterns (footprints) was employed to identify small molecules compatible with putative binding pockets at the internal interface of the NHR helices at the core native viral six-helix bundle. From a screen of ∼2.8 million compounds using the DOCK program, 120 with favorable energetic and footprint overlap characteristics were purchased and experimentally tested leading to two compounds with favorable cell-cell fusion (IC50) and cytotoxicity profiles. Importantly, both hits were identifi

SUBMITTER: Allen WJ 

PROVIDER: S-EPMC4459904 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature