HIV Integrase - Biology and Inhibitor Design
Pp. 185-265 (81)
Victoria Hann and Mark Ashton
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.
Allosteric, chelation, dolutegravir, elvitegravir, integrase,
LEDGF/p75, PIC, 3’-processing, strand transfer, raltegravir, retrovirus.
Department of Pharmacy, Health and Wellbeing, University of Sunderland, UK.