In-silico analysis of ectodomain G protein of Respiratory Syncytial Virus

Respiratory Syncytial Virus (RSV) is one of the most important pathogen of acute lower respiratory tract infections (ALRI) in pediatric population across the globe. The G protein of RSV helps in the attachment of virion with the host cell receptor. It is the neutralizing antigen and therefore a vaccine candidate as well as the target for drug designing studies. The present study describes the three-dimensional structure of the ectodomain region of G protein by homology modeling. The model revealed different binding pockets and tunnels of the G protein. Further, docking of the receptor protein with three different ligands (cathepsin L, benzimidazole and protamine) revealed high binding energies and their interacting residues. The selected ligands might be used as potential lead molecules for future drug designing studies against RSV. In addition, the elaborate experimental validations on cytotoxicity and pharmacodynamics of these inhibitors will provide insight into the detailed mechanism of inhibition of viral replication by these ligands. Further, the in-silico mutational analysis of the G protein suggested that the amino acid changes may stabilize or de-stabilize the protein structure that might affect the structure-function relationship. Determination of complete three-dimensional structure of the G protein and description of protein-inhibitor interaction is envisaged to facilitate the drug designing efforts.