Teicoplanin is a glycopeptide antibiotic effective against several bacterial infections, has exhibited promising therapeutic efficiency against COVID-19 in vitro , and the rationale for its use in COVID-19 is yet to be recognized. Hence, in this study a number of molecular modeling techniques were employed to decrypt the mechanistic insight of teicoplanin interaction with several COVID-19 drug targets. Initially, molecular docking was employed to study the teicoplanin interaction with twenty-five SARS-CoV-2 structural and non-structural proteins which was followed by molecular mechanics/generalized Born surface area (MM/GBSA) computation for binding energy predictions of top ten models from each target. Amongst all macromolecular targets, the N-terminal domain of the nucleocapsid protein displayed the strongest affinity with teicoplanin showing binding energies of −7.4 and −102.13 kcal/mol, in docking and Prime MM/GBSA, respectively. Thermodynamic stability of the teicoplanin-nucleocapsid protein was further probed by molecular dynamics simulations of protein–ligand complex as well as unbounded protein in 100 ns trajectories. Post-simulation MM-GBSA computation of 50 frames extracted from simulated trajectories estimated an average binding energy of −62.52 ± 12.22 kcal/mol. In addition, conformational state of protein in complex with docked teicoplanin displayed stable root-mean-square deviation/fluctuation. In conclusion, computational investigation of the potential targets of COVID-19 and their interaction mechanism with teicoplanin can guide the design of novel therapeutic armamentarium for the treatment of SARS-CoV-2 infection. However, additional studies are warranted to establish the clinical use or relapses, if any, of teicoplanin in the therapeutic management of COVID-19 patients.
【저자키워드】 SARS-CoV-2, docking, molecular dynamics, Teicoplanin, MM/GBSA, 【초록키워드】 COVID-19, Treatment, SARS-COV-2 infection, molecular docking, in vitro, binding energy, nucleocapsid protein, Molecular dynamics simulation, Protein, stability, management, therapeutic, non-structural protein, trajectory, target, targets, molecular, Bacterial infections, mechanism, COVID-19 patients, N-terminal domain, antibiotic, Interaction, Efficiency, computation, Trajectories, Clinical use, Frame, complex, average, binding energy prediction, effective, addition, exhibited, macromolecular, conformational, docked, Initially, 【제목키워드】 COVID-19, drug, target,