Using the Pharmacophoric features of Azithromycin to design potential SARS-CoV-2 inhibitor

Abstract

The outbreak of novel coronavirus (SARS-CoV-2) found in Wuhan China is rapidly spreading to all nations of the world. Currently, there are no approved drugs for the treatment of the novel coronaviral disease. Meanwhile, repositioning of some antibiotics, antiviral and antimalaria drugs have been employed. In this study, we used azithromycin as a model drug to virtual screen the ZINC database and the molecules obtained were docked against SARS-CoV-2 protein with PDB code: 5r7y. The best five ligands with high affinity for the target protein was compared with the reference molecule (Azithromycin). The docking score for the predicted ligands with high affinity for the target protein include ZINC10635972 (-6.3 kcal/mol), ZINC02651653 (-6.2 kcal/mol), ZINC09728215 (-6.2 kcal/mol), ZINC15003138 (-6.1 kcal/mol), ZINC89836288 (-6.1 kcal/mol) and azithromycin (+28.2 kcal/mol). The lead molecule (ZINC10635972) was observed to interacted with LUE 141, ASN 142, SER 144, SER 46, GLY 189, GLU 166, MET 165, HIS163, MET 49, HIS 164, PHE 140, GLY 143,THR 25, CYS 145, HIS 41, CYS 44 and THR 45. Meanwhile, hydrogen bond was predominant in the ZINC10635972-5r7y interaction. The lead molecule demonstrated good pharmacokinetics properties, drug-like characteristic and moderate chemical reactivity index. Besides, ZINC10635972 was noticed to fit the class 5 toxicity index. Hence, ZINC10635972 is a promising compound that should be further examined as drug candidates before clinical evaluation.

Electrostatic Potential Mapped onto Electron Density Surface, ADME, Molecular Docking and Molecular Dynamics Simulations of Some Indolin-2-one Analogues as Cytochrome C Peroxidase Inhibitors

“…It has been hypothesised that all of the ligands satisfy the criteria of RO5. Previous research [30][31][32][33][34] have anticipated that compounds that obeyed RO5 will have a low attrition rate during the drug development process.…”