Computer-Aided Perspective for the Design of Flexible HIV Non- Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): de-novo Drug Design, Virtual Screening and Molecular Dynamics Simulations
Mahmoud E. S. Soliman.
Flexible hydroquinone-based compounds were previously proposed as potential mutant-resistant NNRTIs inhibitors,
however, experimental or computational evidences did not support this proposal. Herewith, using an integrated
in-silico computational approach involving de-novo drug design, structure-based virtual screening (SBVS), molecular dynamics
simulations and post-dynamic per-residue binding energy decomposition analysis, the binding affinity as well as
the interaction landscape of novel flexible hydroquinone-based compounds were investigated to explore their activity as
potential NNRTIs. The proposed leads were found to exhibit improved binding affinity when compared to FDA-approved
NNRTIs, rilpvirine, nevirapine and efavirenz, however, the bioavailability profile of these compounds could hamper their
uses as effective drugs. Results obtained from this extensive study could assist medicinal and biochemistry researchers
with further experimental investigations.
Keywords: Flexible HIV-1 inhibitors, Non-nucleoside reverse transcriptase inhibitors, de-novo drug design, Virtual screening,
Molecular dynamic simulations.
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