Chapter 6

HIV Integrase - Biology and Inhibitor Design

Victoria Hann and Mark Ashton

Abstract

In recent years, HIV integrase has emerged as an important target for the development of new HIV inhibitors. Following the synthesis of viral DNA by reverse transcriptase, integrase performs two functions; 3’-processing and strand transfer/ integration. The catalysis of both functions by the enzyme relies on the presence of magnesium ions (Mg2+) in the active site. All three of the current FDA approved integrase inhibitors operate as strand transfer inhibitors and have chelation of the Mg2+ ion as an integral part of their respective pharmacophores. Interesting new developments in the field involve the targeting of one or more of the range of cellular cofactors involved in the integration process and inhibitors with a novel mode of action known as allosteric inhibitors.

Total Pages: 185-265 (81)

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