The current status of the NNRTI family of antiretrovirals used in the HAART regime against HIV infection

• Type: Another Publication in an International Scientific Journal
• Date: 2008

Authors

Silvia Martins (Author) Other; Maria Joao Ramos (Author) FCUP; Pedro Alexandrino Fernandes (Author) FCUP

Journal

Title: Current Medicinal Chemistry

Vol. 15 No. 22

Pages: 1083-1095

ISSN: 0929-8673

Publisher: Bentham Science

Indexing

ISI Web of Knowledge - 55 Citations

Scopus - 62 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-003-ZKR

DOI: 10.2174/092986708784221467

Abstract (EN): Acquired immunodeficiency syndrome (AIDS) remains, after 25 years of its discovery, as one of the major threats to human life. Reverse Transcriptase is an essential enzyme for virus replication, and therefore constitutes a major target in HIV-1 therapy. Among the different types of drugs targeting RT, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) act by binding in an induced-fit allosteric pocket. In this review, we explore the several NNRTIs' structures and binding interactions, as well as their mechanisms of action. The conformational changes that they cause in RT and their effects on the topology of the active site are discussed. The emergence of mutant, resistant viruses is analysed, focussing on the mutations responsible for the loss of antiviral efficacy of NNRTIs. Explanations for the role of those mutations are presented. Emergent drugs in the pipeline, together with the underlying strategies for drug development, are also analysed.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13