hiv-1 ribonuclease h structure, catalytic mechanism and inhibitorshiv - 1 h核糖核酸酶的结构、催化机理和抑制剂.pdfVIP

Viruses 2010, 2, 900-926; doi:10.3390/v2040900 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review HIV-1 Ribonuclease H: Structure, Catalytic Mechanism and Inhibitors Greg L. Beilhartz and Matthias Götte * Department of Microbiology and Immunology, McGill University, Lyman Duff Medical Building (D6), 3775 University St., Montreal, QC, H3A 2B4, Canada * Author to whom correspondence should be addressed; E-Mail: matthias.gotte@mcgill.ca; Tel.: +1-514-398-1365; Fax: +1-514-398-7052. Received: 28 January 2010; in revised form: 22 March 2010 / Accepted: 24 March 2010 / Published: 30 March 2010 Abstract: Since the human immunodeficiency virus (HIV) was discovered as the etiological agent of acquired immunodeficiency syndrome (AIDS), it has encouraged much research into antiviral compounds. The reverse transcriptase (RT) of HIV has been a main target for antiviral drugs. However, all drugs developed so far inhibit the polymerase function of the enzyme, while none of the approved antiviral agents inhibit specifically the necessary ribonuclease H (RNase H) function of RT. This review provides a background on structure-function relationships of HIV-1 RNase H, as well as an outline of current attempts to develop novel, potent chemotherapeutics against a difficult drug target. Keywords: HIV; reverse transcriptase; RNa