Evaluation of the interaction between potent small molecules against the Nipah virus Glycoprotein in Malaysia and Bangladesh strains, accompanied by the human Ephrin-B2 and Ephrin-B3 receptors; a simulation approach

Abstract

In late September 1998 the first human case of Nipah virus (NiV) having been manifested in Malaysia with severe encephalitis and respiratory symptoms. Then, based on the viral genomic mutations two main strains (NiV-Malaysia and NiV-Bangladesh) have spread across the world. In the face of this biosafety level 4 pathogen with highly pandemic potential, no licensed molecular therapeutics have been approved. Considering the role of NiV attachment Glycoprotein in viral transmission, identifying small molecules that can be repurposed for inhibiting the Glycoprotein attachment, and also the viral receptors in human cells (Ephrin-B2 and Ephrin-B3) as the significant anti-NiV treatment were discussed. Thus, to prospect seven potential anti-COVID-19 drugs with clinical effectiveness (Pemirolast, Nitrofurantoin, Isoniazid Pyruvate, Eriodictyol, Cepharanthine, Ergoloid, and Hypericin) against NiV-G, Ephrin-B2, and Ephrin-B3 receptors, an annealing simulation, ligand-based pharmacophore modeling, and molecular docking simulations were implemented. Based on the annealing analysis, Pemirolast (pem) against efnb2 protein also Isoniazid Pyruvate (iso) against efnb3 receptor were repurposed as the best small molecule candidates. Moreover, Cepharanthine (ceph), and Hypericin (hyp) with noteworthy interaction values are the top Glycoprotein inhibitors in Malaysia and Bangladesh strains. Additionally, molecular docking calculation showed their binding affinity scores which are related to efnb2-pem (-7.1 kcal/mol), efnb3-iso (-5.8 kcal/mol), gm-hyp (-9.6 kcal/mol), gm-ceph (-10.1 kcal/mol), gb-ceph (-9.2 kcal/mol). Our computational research not only minimizes the challenge of time-consuming but also meets our precautionary demand for options to handle any new variants of the Nipah virus that might emerge in the future.

Integrated Computational Biophysics approach for Drug Discovery against Nipah Virus

“…Therefore, they are characterized by the presence of multiple aromatic rings with hydroxyl groups that allow interactions with proteins through hydrogen bridges [50]. These chemical characteristics make procyanidins an attractive target for drug design approaches such as ligand-based pharmacophore modeling [51].…”