Medical Laboratory Journal (Nov 2022)
Effective Binding Affinity of Inhibitor N-(3-(Carbamoylamino) Phenyl) Acetamide against the SARS-CoV-2 NSP13 Helicase
Abstract
Background and objectives: The outbreak of coronavirus disease 2019 (COVID-19) has become a global health emergency. The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) NSP13 helicase plays an important role in SARS-CoV-2 replication and could serve as a target for the development of antivirals. The objective of the study was to perform homology modeling and docking analysis of SARS-CoV-2 NSP13 helicase as a drug target. Methods: The structure and function of SARS-CoV-2 NSP13 helicase were predicted by in-silico modeling studies. The SWISS-MODEL structure assessment tool was used for homology modeling and visual analysis of the crystal structure of the protein. The validation for structure models was performed using PROCHECK. Model quality was estimated based on the QMEAN and ProSA. The MCULE-1-Click docking and InterEvDock-2.0 server were used for protein-ligand docking. Results: The SARS-CoV-2 NSP13 helicase model corresponded to probability confirmation with 90.9% residue of the core section, which highlights the accuracy of the predicted model. ProSA Z-score of -9.17 indicated the good quality of the model. Inhibitor N-(3-(carbamoylamino) phenyl) acetamide exhibited effective binding affinity against the NSP13 helicase. The docking results revealed that Lys-146, Leu-147, Ile-151, Tyr-185, Lys-195, Tyr-224, Val-226, Leu-227, Ser-229 residues exhibit good binding interactions with inhibitor ligand N-(3-(carbamoyl amino) phenyl) acetamide. Conclusion: Hence, the proposed inhibitor could potently inhibit SARS-CoV-2 NSP13 helicase, which is thought to play key roles during viral replication. The results of this study indicate that N-(3-(carbamoylamino) phenyl) acetamide could be a valuable lead molecule with great potential for SARS-CoV-2 NSP13 helicase inhibition.
