DRUG REPURPOSING: IDENTIFICATION OF POTENTIAL DRUG TARGETS AGAINST NONSTRUCTURAL PROTEIN 1 (NSP-1) OF SARS-COV-2 THROUGH MOLECULAR DOCKING AND MOLECULAR DYNAMIC SIMULATION USING FDA APPROVED DRUGS

Abstract

Since its pandemic in 2019, SARS-CoV-2 has badly affected the countries around the globe. There is no FDA approved drug for the treatment of the disease. In this study, we evaluated potential targets against non-structural protein-1 (Nsp-1), which is crucial in disturbing host-translational machinery. As the completecrystal structure of the Nsp-1 was not available, we used I-TASSER for making the complete structure of the protein. The structure was verified using ERRATand PROVEAN. As the previous studies had reported different binding sites for this protein, we used blind docking of Nsp-1 with 2225 FDA approved drugsusing AutoDock Vina. Based upon the residue interactions obtained from the blind docking, we selected C-terminal of Nsp-1 for specific docking against FDAapproved drugs. Based upon the docking results, Glycyrrhizin was found to be suitable drug showing strong interactions. We further verified the glycyrrhizin-Nsp-1 complex by analyzing the trajectory for 60 ns, by comparing with individual protein. RMSD analysis during the trajectory and RMSF analysis alsosuggested the stability of the protein-ligand complex and resulted in 49 hydrogen bonds during the simulation process. The study suggests that Glycyrrhizin can act as potential inhibitors against Nsp-1 of SARS-COV-2.