Current Pharmaceutical Design - Volume 9, Issue 22, 2003

The selection of topics and authors was made with the intention to complement the first issue of anti-HIV Drug Design (Current Pharmaceutical Design, 2002, Volume 8, number 8). These articles present alternative approaches other than available chemotherapeutic agents against Human Immunodeficiency Virus (HIV). Several HIV protease inhibitors (PIs) show suboptimal pharmacological and pharmacokinetics properties Read More

Despite the efficiency of the present polytherapies against AIDS, HIV replication continues indicating difficulties in drug adherence, drug-drug interactions, resistance issues, and the existence of reservoirs or sanctuaries for the virus. Moreover, most of the current FDA-approved HIV protease inhibitors (PIs) display disadvantageous physicochemical and pharmacological properties such as low water solubility, low oral Read More

The worldwide epidemic of HIV / AIDS urges the development of an effective vaccine. With the identification of HIV as the cause of AIDS about two decades ago, it was once expected that a preventive vaccine would follow closely behind. But the early promise of HIV envelope gp120 as a preventive vaccine was not fulfilled. Broadly neutralizing antibodies and HIV-specific cytotoxic T lymphocytes (CTL) are two immune effe Read More

Integration of viral DNA into host cell chromosomal DNA to form a provirus is an essential step in the viral life cycle. This process is mediated by integrase (IN), a 32 KDa viral enzyme. The unique properties of IN makes it an ideal target for drug design. First, there are no cellular homologues to IN and the reactions catalyzed by IN are unique. Second, IN is absolutely required for viral replication and mutations in a number of k Read More

Acquired immunodeficiency syndrome (AIDS) is a worldwide epidemic caused by infection with HIV, a human retrovirus. Proteolysis occurs at many points of the retroviral life-cycle, and these events can be considered as targets for chemotherapy. The most well-known proteolytic action in the retroviral life-cycle is the processing of the Gag and Gag-Pro-Pol polyproteins with the virally encoded protease at the late phase of viral Read More

Among the non-nucleoside reverse transcriptase inhibitors, 1-[2-hydroxyethoxy-methyl]-6-(phenylthio) thymine (HEPT) derivatives have proved to be potent and selective inhibitors of human immunodeficiency virus (HIV-1). They are able to completely suppress virus replication in cell cultures. The quantitative structure-activity relationships (QSAR) try to describe the association between biological activities of a group of congen Read More