A Hybrid pharmacophore and structure-based drug design approach, aided by binding mode analysis, molecular
dynamics simulations and per-residue energy contribution calculations, was used to design five novel structural scaffolds
as potential bifunctional anti-HIV/TB inhibitors. Binding free energy calculations demonstrated that the proposed
compounds exhibited better binding affinities towards HIV PR and BlaC enzymes when compared to prototype drugs, darunavir
and meropenem, respectively. The lead design strategy presented in this work could serve as a useful tool for developing
bifunctional inhibitors against wide range of biological targets.
Keywords: Dual acting HIV/TB inhibitors, HIV-1 protease inhibitors, B-lactamase inhibitors, TB, computer-aided drug design,
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