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Cristina Cantale

The Viral Integrases

The Integrase Protein

Therapeutical implications

Integration of viral DNA is a fundamental step in life cycle of retroviruses, necessary for the production of progeny viruses.
Mutation in the 3' proximal portion of the gene of HIV, in the region coding for IN, produce mutants identical to the wild type except for integration. Proviral DNA is not formed and the infection slowly disappears(Goff S.P.,92). However the absolute requirement of integration for productive HIV-1 infection has not yet been unequivocally established. On the contrary, examples are reported about virus infection without integration.
In any case, integration is a target for designing drugs against retroviruses, mainly with reference to AIDS.
A great research effort is going on to identify inhibitors of different steps of integration that can be used at therapeutical level.

Some substances that show inhibition against the catalytic activity of IN, including caffeic acid phenylethyl ester (CAPE) (Fesen M.R. et al., 93), topoisomerase inhibitors and bis-catechols have been reported. Often they are not selective for IN.
Recently a new class of compounds derived from caffeic acid has been tested , obtaining encouraging results. These compounds are two dicaffeoylquinic acids (DCQAs) extracted from medicinal plants (Achyrocline satureioides), together with a synthetic compound, L-chicoric acid (Robinson W.E. et al., 96). They are reported to be inhibitors of HIV-1 in biochemical assays and also in in vitro assays of disintegration, the latter evidence suggesting an interaction with the catalytic core domain of HIV IN. The effect on host DNA is unknown but their selectivity in tissue culture is promising.
Besides, a Fab fragment (Fab 35) of a specific monoclonal antibody (MAb35) has been characterized (Barsov E.V. et al., 96). It is able to bind to an epitope on the C-terminal domain of HIV-1 IN and block every activity. It has been suggested that it interacts with the multimerization of IN.

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Last updated 25th Oct '96