Computational prediction of nimbanal as potential antagonist of respiratory syndrome coronavirus

Aanuoluwa Eunice Adegbola; Olumide Samuel Fadahunsi; Abdulahi Alausa; Ayodeji Zabdiel Abijo; Toheeb Adewale Balogun; Taiwo Sarah Aderibigbe; Banjo Semire; Peter Ifeoluwa Adegbola

doi:10.1016/j.imu.2021.100617

Computational prediction of nimbanal as potential antagonist of respiratory syndrome coronavirus

Inform Med Unlocked. 2021:24:100617. doi: 10.1016/j.imu.2021.100617. Epub 2021 May 28.

Authors

Aanuoluwa Eunice Adegbola¹, Olumide Samuel Fadahunsi², Abdulahi Alausa², Ayodeji Zabdiel Abijo³, Toheeb Adewale Balogun⁴, Taiwo Sarah Aderibigbe⁵, Banjo Semire¹, Peter Ifeoluwa Adegbola²

Affiliations

¹ Department of Pure and Applied Chemistry, Faculty of Pure and Applied Sciences, Ladoke Akintola University of Technology, Nigeria.
² Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Nigeria.
³ Department of Anatomy, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Nigeria.
⁴ Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Nigeria.
⁵ Department of Science Laboratory Technology, Biological Sciences, Microbiology Unit, the Oke Ogun Polytechnic Saki, Nigeria.

Abstract

The high pathogenic nature of the Middle East Respiratory coronavirus (MER) and the associated high fatality rate demands an urgent attention from researchers. Because there is currently no approved drug for the management of the disease, research efforts have been intensified towards the discovery of a potent drug for the treatment of the disease. Papain Like protease (PLpro) is one of the key proteins involved in the viral replication. We therefore docked forty-six compounds already characterized from Azadirachta indica, Xylopia aethipica and Allium cepa against MERS-CoV-PLpro. The molecular docking analysis was performed with AutoDock 1.5.6 and compounds which exhibit more negative free energy of binding, and low inhibition constant (Ki) with the protein (MERS-CoV-PLpro) were considered potent. The physicochemical and pharmacokinetic properties of the compounds were predicted using the Swissadme web server. Twenty-two of the compounds showed inhibition potential similar to dexamethasone and remdesvir, which had binding affinity of -6.8 and -6.3 kcal/mol respectively. The binding affinity of the compounds ranged between -3.4 kcal/mol and -7.7 kcal/mol whereas; hydroxychloroquine had a binding affinity of -4.5 kcal/mol. Among all the compounds, nimbanal and verbenone showed drug likeliness, they did not violate the Lipinski rule neither were they inhibitors of drug-metabolizing enzymes. Both nimbanal and verbenone were further post-scored with MM/GBSA and the binding free energy of nimbanal (-25.51 kcal/mol) was comparable to that of dexamethasone (-25.46 kcal/mol). The RMSD, RMSF, torsional angle, and other analysis following simulation further substantiate the efficacy of nimbanal as an effective drug candidate. In conclusion, our study showed that nimbanal is a more promising therapeutic agent and could be a lead for the discovery of a new drug that may be useful in the management of severe respiratory coronavirus syndrome.

Keywords: Dexamethasone; Medicinal plants; Molecular dynamics; Nimbanal; Papain like protease; Respiratory syndrome coronavirus.