PPS96 Projects PPS96 Projects
Cristina Cantale
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.
PPS96
List of Contents
3D structure
About phylogenyReferences
Last updated 25th Oct '96