title: Advances in non-peptidomimetic HIV protease inhibitors.
abstract: HIV protease plays a crucial role in the viral life cycle. It can cleave a series of heptamers in the viral Gag and GagPol precursor proteins to generate mature infectious virus particles. Successful inhibition of the protease will prevent this maturation step and hence block the spreading of HIV. However, the rapid emergence of drug resistance makes it urgent to develop new HIV protease inhibitors to combat the global disease. Besides, poor oral bioavailability, unacceptable side effects, high treatment cost and pill burden also trouble the application of HIV protease inhibitors. In such situations, non-peptidomimetic HIV protease inhibitors have drawn an increasing interest as a potential therapeutic option due to their small molecular weight, favorable bioavailability, high stability in vivo, low resistance and cost of production. In this review, we present the recent advances in non-peptidomimetic HIV protease inhibitors. Their design strategies, biological activities, resistance profiles, as well as clinical application will also be discussed.
authors.forename: X
authors.initials: X
authors.lastname: Pang
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. professorgxzhai@126.com.
authors.forename: G
authors.initials: G
authors.lastname: Zhai
mesh_terms: D015195:Drug Design; D024882:Drug Resistance, Viral; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology; D006678:HIV / Q000187:drug effects / Q000201:enzymology*; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D037741:Fullerenes; D017320:HIV Protease Inhibitors; D009942:Organometallic Compounds; D011753:Pyrones; D011759:Pyrrolidines; D013449:Sulfonamides; D014508:Urea; D016333:HIV Protease