The Efficacy of Flavonoids for the inhibition of Measles: A Computational Study

Measles is a leading cause of death in children in countries with suboptimal vaccination coverage. The disease is caused by a negative-strand RNA virus called measles virus. It uses receptors to invade cells and later establish infection namely the signalling lymphocyte activation molecule f1 (SLAMF1) and nection-4 which is expressed in the lung epithelium. Till date, there is no specific drug for the treatment of measles. Thus, this research work explored twenty (20) bioactive compounds (flavonoids derivatives) aimed at searching for effective drug candidates for the treatment of measles. Among the twenty ligands, eight (8) passed the famous Lipinski’s rule of five and good oral bioavailability via Swiss ADMET study. Optimization of these ligands was achieved using Spartan14 to generate molecular descriptors to ascertain their bio-reactivity. These ligands were further docked against the active sites of hemagglutinin protein (PDB ID: 2ZB5) using PyRx to determine the interaction. The major amino acids residues found in the best flavonoid, Quercetin 3-sulfate are SER:353, SER:512, SER:439, SER:511, PRO:457, PRO:458,LEU:510, MET:459, LYS:460 through van der Waals and Pi-Alkyl bonds. While the standard drug, Ribavirin interacted with VAL:220,ILE:219,GLN:567,ARG:355,SER:353,GLU:565 via the van der Waals, Conventional Hydrogen Bond. Six ligands had better docking scores than the standards used. However, Quercetin 3-sulfate was the best ligands with binding affinity, -8.9 kcal/mol while Quercetin 3-caprylate, -6.7 kcal/mol with the worst binding affinity. The molecular dynamic study revealed a more stable Quercetin 3-sulfate-protein complex compared to Ribavirin-protein complex. Therefore, Quercetin 3-sulfate could serve as a potential antimeasles drug.