title: Unorthodox inhibitors of HIV protease: looking beyond active-site-directed peptidomimetics.
abstract: HIV protease (PR) is a key target for antiviral drugs, and HIV protease inhibitors (PIs) are a prime example of successful structure-based drug design. PIs show clear therapeutic benefits, but their efficacy can be compromised by poor bioavailabilitity, unwanted side effects, and most importantly, development of antiviral drug resistance. Therefore, the quest for novel, highly active compounds with improved resistance profiles, better pharmacokinetic properties, and fewer adverse effects continues. In particular, the problem of cross-resistance could be circumvented by identifying novel compounds that show different binding modes to HIV PR than the current clinical inhibitors.
authors.forename: Jiri
authors.initials: J
authors.lastname: Schimer
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic. konval@uochb.cas.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Konvalinka
mesh_terms: D020134:Catalytic Domain; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy / Q000379:methods*; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D017320:HIV Protease Inhibitors; D057786:Peptidomimetics; D016333:HIV Protease