[Progress in antiretroviral drugs].

HIV-1, causative agent of acquired immunodeficiency syndrome, was identified in the early 1980s . The plague quickly spread throughout the world and today 40 million people are living with HIV/AIDS. The first anti-HIV drug "zidovudine", was discovered in 1985, and many other inhibitory compounds have been developed successfully in the last decade. Today, three classes 17 antiretroviral drugs are available in Japan. This article overviews the history of anti-HIV drug discovery, present HIV-1 treatment, and on-going drug discovery.

[1]  N. Parkin,et al.  Activities of Atazanavir (BMS-232632) against a Large Panel of Human Immunodeficiency Virus Type 1 Clinical Isolates Resistant to One or More Approved Protease Inhibitors , 2003, Antimicrobial Agents and Chemotherapy.

[2]  J Desmyter,et al.  Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro. , 1987, Biochemical and biophysical research communications.

[3]  J A Grobler,et al.  Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. , 2000, Science.

[4]  I B Duncan,et al.  Rational design of peptide-based HIV proteinase inhibitors. , 1990, Science.

[5]  E. Clercq Potential of acyclic nucleoside phosphonates in the treatment of DNA virus and retrovirus infections. , 2003 .

[6]  L. Resnick,et al.  U-90152, a potent inhibitor of human immunodeficiency virus type 1 replication , 1993, Antimicrobial Agents and Chemotherapy.

[7]  Jan Balzarini,et al.  In Vitro Evaluation of Nonnucleoside Reverse Transcriptase Inhibitors UC-781 and TMC120-R147681 as Human Immunodeficiency Virus Microbicides , 2004, Antimicrobial Agents and Chemotherapy.

[8]  H. Mitsuya,et al.  Spirodiketopiperazine-Based CCR5 Inhibitor Which Preserves CC-Chemokine/CCR5 Interactions and Exerts Potent Activity against R5 Human Immunodeficiency Virus Type 1 In Vitro , 2004, Journal of Virology.

[9]  L. Naeger,et al.  ATP-Dependent Removal of Nucleoside Reverse Transcriptase Inhibitors by Human Immunodeficiency Virus Type 1 Reverse Transcriptase , 2002, Antimicrobial Agents and Chemotherapy.

[10]  J F Davies,et al.  Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. , 1997, Journal of medicinal chemistry.

[11]  Myriam Witvrouw,et al.  New Class of HIV Integrase Inhibitors that Block Viral Replication in Cell Culture , 2002, Current Biology.

[12]  David A. Stock,et al.  BMS-232632, a Highly Potent Human Immunodeficiency Virus Protease Inhibitor That Can Be Used in Combination with Other Available Antiretroviral Agents , 2000, Antimicrobial Agents and Chemotherapy.

[13]  E. Furfine,et al.  Preclinical Pharmacology and Pharmacokinetics of GW433908, a Water-Soluble Prodrug of the Human Immunodeficiency Virus Protease Inhibitor Amprenavir , 2004, Antimicrobial Agents and Chemotherapy.

[14]  S. Vasavanonda,et al.  ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Lambert,et al.  Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Michael A. Parniak,et al.  A Tight-Binding Mode of Inhibition Is Essential for Anti-Human Immunodeficiency Virus Type 1 Virucidal Activity of Nonnucleoside Reverse Transcriptase Inhibitors , 2002, Antimicrobial Agents and Chemotherapy.

[17]  E. De Clercq,et al.  Marked in vivo antiretrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine, a selective anti-human immunodeficiency virus agent. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Amy S. Espeseth,et al.  Diketo acid inhibitor mechanism and HIV-1 integrase: Implications for metal binding in the active site of phosphotransferase enzymes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  P. Darke,et al.  L-735,524: the design of a potent and orally bioavailable HIV protease inhibitor. , 1994, Journal of medicinal chemistry.

[20]  Richard A. Rode,et al.  Identification of Genotypic Changes in Human Immunodeficiency Virus Protease That Correlate with Reduced Susceptibility to the Protease Inhibitor Lopinavir among Viral Isolates from Protease Inhibitor-Experienced Patients , 2001, Journal of Virology.

[21]  E. De Clercq,et al.  Cellular uptake of phosphonylmethoxyalkylpurine derivatives. , 1991, Antiviral research.

[22]  E. De Clercq,et al.  Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine , 1993, Antimicrobial Agents and Chemotherapy.

[23]  H. Mitsuya,et al.  Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D W Barry,et al.  3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Cervia,et al.  Enfuvirtide (T-20): a novel human immunodeficiency virus type 1 fusion inhibitor. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  David E. Martin,et al.  PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[27]  E. De Clercq,et al.  Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Neil Parkin,et al.  Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. , 2004, The Journal of infectious diseases.

[29]  J. Pagano,et al.  Novel acyclic adenosine analogs inhibit Epstein-Barr virus replication , 1987, Antimicrobial Agents and Chemotherapy.

[30]  D. Smee,et al.  Characterization of Wild-Type and Cidofovir-Resistant Strains of Camelpox, Cowpox, Monkeypox, and Vaccinia Viruses , 2002, Antimicrobial Agents and Chemotherapy.

[31]  M. Wainberg,et al.  Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2'-deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog , 1991, Antimicrobial Agents and Chemotherapy.

[32]  J. Adams,et al.  Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. , 1990, Science.

[33]  Mark Embrey,et al.  A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[34]  P. Anderson,et al.  L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase , 1995, Antimicrobial agents and chemotherapy.