Virtual Screening and Toxicology Prediction of Novel Potential Non- Nucleoside Reverse Transcriptase Inhibitors

The enzyme reverse transcriptase (RT) is essential in the replication of human immunodeficiency virus (HIV). Non-nucleoside reverse transcriptase inhibitors or NNRTI's are a promising class of anti-HIV drugs, which block the chemical step of DNA polymerization reaction by binding at the allosteric site of RT, leading to a viral suppression. A major limitation to the success of therapy with NNRTIs is the rapid development of drug-resistant mutants. In this work we have used molecular modeling, virtual screening, flexible docking, molecular interaction field, pharmacophoric alignment, toxicology predictions, and molecular dynamics simulations in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over K103N RT enzyme, which is the most common mutation to emerge.