Discovery and optimization of novel small-molecule HIV-1 entry inhibitors using field-based virtual screening and bioisosteric replacement.

ABSTRACT: With the emergence of drug-resistant strains and the cumulative toxicities associated with current therapies, demand remains for new inhibitors of HIV-1 replication. The inhibition of HIV-1 entry is an attractive, yet underexploited therapeutic approach with implications for salvage and preexposure prophylactic regimens, as well as topical microbicides. Using the combination of a field-derived bioactive conformation template to perform virtual screening and iterative bioisosteric replacements, coupled with in silico predictions of absorption, distribution, metabolism, and excretion, we have identified new leads for HIV-1 entry inhibitors.

SUBMITTER: Tuyishime M 

PROVIDER: S-EPMC4355043 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature