In-silico Study of Baricitinib as Inhibitor of AP2-Associated Protein Kinase 1 (AAK1) for the treatment of SARS-CoV-2 (Research Article)

Author(s): Monideepa Guha and Aditya Narayan Singh

Abstract: Baricitinib is an effective disease-modifying anti-rheumatic drug which has gained importance in treatment of SARS-CoV-2 by targeting the Adapter Protein-2 Associated protein Kinase 1 (AAK1) which is involved in clathrin-mediated endocytosis. Using the available protein data, it was found that Lys74 residue in the protein is involved in ATP-binding. In the present study, we aimed at visualizing the binding of baricitinib within the active site AAK1. The amino acids of AAK1 invoalved in the active site were visualized using Caver Web tools and molecular docking of baricitinib showed that it interacted with three amino acids of the active site namely Gly55, Cys129 and Asp194 with polar bonds and binding energy of -10.76 kcal/mol. Lys74 was found to interact with the drug using an alkyl bond of length 4.96Å which shows that the drug serves as a competitive kinase inhibitor for the enzyme by competing with ATP in the active site of the protein. ADME analysis was also performed for the drug to analyse its lipophilicity, topographical polar surface area and intestinal permeability when administered to a patient.

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