With the goal of suggesting dual inhibitors of HIV
reverse transcriptase (RT) and integrase (IN), herein we report the molecular
docking of an initial set of 556 compounds related to the pyridinone class.
Docking with multiple crystallographic structures of HIV-1 RT led to 160
potential binders of RT interacting with key amino acid residues at the
enzyme’s allosteric site. Compounds selected from the docking with RT were
further docked with a crystallographic structure of HIV-1 IN. A total of 31
structures had the potential to make contacts with Mg2+ ions located
in a small space between DNA and IN. Interactions with Mg2+ ions are
relevant because they participate in the stabilization of the IN-DNA complex.
In conclusion, 31 compounds synthetically accessible are proposed as dual
inhibitors of RT and IN. It is hypothesized that the suggested compounds will
inhibit RT by occupying the allosteric site for NNRTIs and will inhibit the
catalytic activity of IN by destabilizing the IN-DNA complex. The main
perspective of this work is the synthesis and biological testing of the
candidate molecules.
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