Homology Modelling and Molecular Docking Studies to Discover Potent Inhibitors of CD169 in PRRSV Infection

Abstract

CD169 is one of the putative receptors of porcine reproductive and respiratory syndrome virus, also plays a major role in PRRSV infection. Computational methods including, homology modelling, molecular docking analysis and molecular dynamics simulations carried out to investigate 3D structure and potent inhibitors of CD16. Homology modelling and molecular docking were done by Maestro 10.6. A 3D structure of CD169 was obtained through homology modelling. It was later subjected protein-ligand interaction by molecular docking study. The docking results showed top ten hits compounds with the docking score energies, among those compounds MOL002433 (3R,8S,9R,10R,13R,14S,17R)-3-hydroxy-4,4,9,13,14-pentamethyl-17-[(E,2R)-6-methyl-7-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhept-5-en-2-yl]-1,2,3,7,8,10,12,15,16,17-decahydr) had the best docking score energy -8.095 kcal/mol and showed significant binding affinity and interactions with CD169 receptor active site, respectively form H bond with residues ASP-40, SER-104, LYS-107 and ASN-92. Furthermore, MD (molecular dynamics) simulations were performed by Amber 16 to investigate the stability of a ligand-protein complex. The analysis of root mean square deviation (RMSD) of CD169 /(3R,8S,9R,10R,13R,14S,17R)-3-hydroxy-4,4,9,13,14-pentamethyl-17-[(E,2R)-6-methyl-7-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhept-5-en-2-yl]-1,2,3,7,8,10,12,15,16,17-decahydr) complex revealed that CD169 protein has more stability when it interacts with the inhibitor. These findings have given us a better understanding of the functional properties and the reaction mechanism of CD169 receptor. Our results will help to identify new leads for drug discovery in PRRSV infection.