Bioinformatics Prediction of Potential Inhibitors For the SARS-CoV-2 NTPase/Helicase Using Molecular Docking and Dynamics Simulation From Organic Phenolic Compounds

authors:

avatar massoud saidijam 1 , * , avatar Negin Khaksarimehr 2 , avatar Mostafa Rezaei-Tavirani ORCID 3 , avatar Amir Taherkhani 4

Department of Molecular Medicine and Genetics, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.
Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Journal of Cellular & Molecular Anesthesia: Vol.6, issue 3; e150255
article type: Original Articles
DOI: https://doi.org/10.22037/jcma.v6i3.34490

how to cite: saidijam M, Khaksarimehr N , Rezaei-Tavirani M, Taherkhani A. Bioinformatics Prediction of Potential Inhibitors For the SARS-CoV-2 NTPase/Helicase Using Molecular Docking and Dynamics Simulation From Organic Phenolic Compounds. J Cell Mol Anesth. 2021;6(3):e150255. https://doi.org/10.22037/jcma.v6i3.34490.

Abstract

Background: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a disorder with human-to-human rapid transmission. Besides several vaccines that have been represented, it is crucial to discover effective drugs to combat this infection in a short-period therapeutic procedure. The NTPase/helicase contributes to playing an important role in the replication of the viral RNA. Materials and methods: We estimated the binding affinity of several natural polyphenolics, commonly found in fruits and vegetables, with the catalytic site of SARS-CoV-2 helicase by molecular docking analysis using the AutoDock tool. The stability of connections between top-ranked components inside the catalytic site of the helicase was evaluated by molecular dynamics (MD) simulations. The most active residues within the catalytic site of the helicase were ranked based on their degree in a phenolics-residue interaction (PRI) network. Results: Amentoflavone, theaflavin 3'-gallate, and procyanidin were estimated to be the most potential effective SARS-CoV-2 helicase inhibitors with the salient inhibition constant value (Ki) at the picomolar scale. The energy of binding of these compounds with the helicase catalytic site was estimated between -13.90 and -12.77 kcal/mol. Asp534 and Leu412 demonstrated more degrees than the other residues. Conclusion: The present study predicts that amentoflavone, theaflavin 3'-gallate, and procyanidin might be helpful for the treatment of COVID-19.