Development of indole compounds as small molecule fusion inhibitors targeting HIV-1 glycoprotein-41.

ABSTRACT: Nonpeptide inhibition of fusion remains an important goal in anti-HIV research, due to its potential for low cost prophylaxis or prevention of cell-cell transmission of the virus. We report here on a series of indole compounds that have been identified as fusion inhibitors of gp41 through a structure-based drug design approach. Experimental binding affinities of the compounds for the hydrophobic pocket were strongly correlated to fusion inhibitory data (R(2) = 0.91), and corresponding inhibition of viral replication confirmed the hydrophobic pocket as a valid target for low molecular weight fusion inhibitors. The most active compound bound to the hydrophobic pocket and inhibited cell-cell fusion and viral replication at submicromolar levels. A common binding mode for the inhibitors in this

SUBMITTER: Zhou G 

PROVIDER: S-EPMC3234170 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature