Molecular docking analysis of novel Non-Nucleoside Reverse Transcriptase Inhibitors in development: implication for rational drug design

Abstract

Background Human immunodeficiency virus (HIV) from a family of retroviruses is a causative organism for acquired immuno deficiency syndrome (AIDS), affecting more than 40 million people worldwide [1]. Reverse transcription of the HIV single-stranded RNA genome into double-stranded DNA is one of the essential key step in the virus replication life-cycle and acts as lucrative target for drug action. Till date, out of 20 anti-HIV drugs approved for the treatment of HIV infection, eleven approved anti-HIV drugs target RT, and encompass three classes of agents that inhibit RT by different mechanisms (Nucleoside Reverse Transcriptase Inhibitors, NRTIs; Non-Nucleoside Reverse Transcriptase Inhibitors, NNRTIs; Nucleotide Reverse Transcriptase Inhibitors, NtRTIs) [2]. The NNRTIs serve as an increasingly important role in the therapy of HIV infection, due to their unique antiviral potency, high specificity and low toxicity. Present work illustrates the probable binding affinity, interatomic contacts and orientation of novel of NNRTIs in development at the allosteric site of the HIV-RT through an iterative computational process and molecular docking to explicate the necessary structural requirement for rational drug design.