HIV-1 regulatory proteins: targets for novel drug development.
Due to the development of HIV-1 resistance to current antiviral drugs and the known toxicity of many of these drugs, there is a clear need to identify and develop novel compounds for use in the treatment of HIV-1 infected patients. The HIV-1 regulatory proteins, Tat and Rev, are required for HIV-1 replication and therefore represent two important viral targets for drug development. Novel drugs that target these proteins would increase the number of available treatment strategies for HIV-1 infection. This could result in better combination therapies in which many different viral targets could be inhibited simultaneously, thereby decreasing the likelihood of selecting for drug-resistant viruses. This review outlines many of the ways that Tat and Rev can be targeted for drug development, describes recently reported lead compounds as inhibitors of these proteins and discusses strategies for implementing drug screens for identifying novel inhibitors.
Ptak
Roger G
RG
Infectious Disease Research Department, Southern Research Institute, 431 Aviation Way, Frederick, Maryland 21701, USA. ptak@sri.org
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D024882:Drug Resistance, Viral; D015694:Gene Products, rev / Q000037:antagonists & inhibitors; D015696:Gene Products, tat / Q000037:antagonists & inhibitors; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D054334:Viral Regulatory and Accessory Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D015694:Gene Products, rev; D015696:Gene Products, tat; D054334:Viral Regulatory and Accessory Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus