title: Virtual screening application of a model of full-length HIV-1 integrase complexed with viral DNA.
abstract: To address the absence of experimental data on the full-length structure of HIV-1 integrase and the way it binds to viral and human DNA, we had previously [Karki, R. G.; Tang, Y.; Burke, T. R., Jr.; Nicklaus, M. C. J. Comput. Aided Mol. Des.2004, 18, 739] constructed models of full-length HIV-1 integrase complexed with models of viral and human DNA. Here we describe the discovery of novel HIV-1 integrase strand transfer inhibitors based on one of these models. Virtual screening methods including docking and filtering by predicted ADME/Tox properties yielded several microM level inhibitors of the strand transfer reaction catalyzed by wild-type HIV-1 integrase.
authors: Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA.
authors: Chenzhong
authors: C
authors: Liao
authors: Rajeshri G
authors: RG
authors: Karki
authors: Christophe
authors: C
authors: Marchand
authors: Yves
authors: Y
authors: Pommier
authors: Marc C
authors: MC
authors: Nicklaus
mesh_terms: D002384:Catalysis; D004279:DNA, Viral / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase