In silico Docking Analysis of the FDA-Approved Drugs on Envelope Protein of SARS CoV-2 Omicron Variant

Abstract

The current pandemic situation is created by the highly evolving SARS coronavirus 2 which is having several mutations in its structural proteins. The structural proteins of SARS CoV-2 include spike (S), Envelope (E), Membrane (M), and Nucleocapsid (N) which are primarily responsible for the infection, transmission, and pathogenesis of the virus. Envelope protein is the smallest of the four proteins containing 75 amino acids with a molecular weight of about 8 kDa. The major functions of the hydrophobic envelope protein include envelope formation, budding, replication, and release of the virion. The presence of mutation on the envelope protein results in improper formation of the pentameric structure and also hinders other functional properties. Our computational analysis majorly focuses on several FDA-approved inhibitory compounds that bind to SARS CoV-2 envelope protein that help in the inhibition of virion formation. The percentage of similarity of the envelope protein between SARS CoV and SARS CoV-2 is approximately 96 percent. The homology-modeled structure of the SARS CoV E protein was downloaded from Protein Model Database (PMDB) and the mutation which was found to be consistent among most of the SARS CoV-2 variants was selected as T9I which is present in the N-terminal region. This mutation was introduced into the SARS CoV Envelope protein and was remodeled. The ligands which were approved by FDA were selected for docking analysis to understand their binding capabilities with the envelope protein. Ligands such as Beta-D-Fucose, Mycophenolic Acid, Castanospermine, 1-Deoxynojirimycin, Nafcillin, Guaifenesin, Nabumetone, Cinametic Acid, Lauric acid were used in our study. The docking simulations revealed that Lauric acid, Nafcillin, Nabumetone, and Mycophenolic acid have high binding energy with the SARS CoV-2 wild type (Wuhan) and mutant E protein of the SARS CoV-2 (Omicron) variant. This Insilico data gives insights to test these high binding compounds in invitro studies to prove their efficacy and the protein-protein interactions of envelope protein with its other partnering proteins. These pharmaceutical compounds are a potential alternative in the future for a novel drug development to treat several emerging variants of SARS CoV-2.