Computational prediction of nimbanal as potential antagonist of respiratory syndrome coronavirus

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

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.