Strong Binding of Leupeptin with TMPRSS2 Protease May Be an Alternative to Camostat and Nafamostat for SARS-CoV-2 Repurposed Drug: Evaluation from Molecular Docking and Molecular Dynamics Simulations

Ramakrishnan, J and Kandasamy, S and Iruthayaraj, A and Magudeeswaran, S and Chinnasamy, K and Poomani, K (2021) Strong Binding of Leupeptin with TMPRSS2 Protease May Be an Alternative to Camostat and Nafamostat for SARS-CoV-2 Repurposed Drug: Evaluation from Molecular Docking and Molecular Dynamics Simulations. In: Applied Biochemistry and Biotechnology .

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Abstract

The unprecedented coronavirus SARS-CoV-2 outbreak at Wuhan, China, caused acute respiratory infection to humans. There is no precise vaccine/therapeutic agents available to combat the COVID-19 disease. Some repurposed drugs are saving the life of diseased, but the complete cure is relatively less. Several drug targets have been reported to inhibit the SARS-CoV-2 virus infection, in that TMPRSS2 (transmembrane protease serine 2) is one of the potential targets; inhibiting this protease stops the virus entry into the host human cell. Camostat mesylate, nafamostat, and leupeptin are the drugs, in which the first two drugs are being used for COVID-19 and leupeptin also tested. To consider these drugs as the repurposed drug for COVID-19, it is essential to understand their binding affinity and stability with TMPRSS2. In the present study, we performed the molecular docking and molecular dynamics (MD) simulation of these molecules with the TMPRSS2. The docking study reveals that leupeptin molecule strongly binds with TMPRSS2 protein than the other two drug molecules. The RMSD and RMSF values of MD simulation confirm that leupeptin and the amino acids of TMPRSS2 are very stable than the other two molecules. Furthermore, leupeptin forms interactions with the key amino acids of TMPRSS2 and the same have been maintained during the MD simulations. This structural and dynamical information is useful to evaluate these drugs to be used as repurposed drugs, however, the strong binding profile of leupeptin with TMPRSS2, suggests, it may be considered as a repurposed drug for COVID-19 disease after clinical trial. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Item Type:	Journal Article
Publication:	Applied Biochemistry and Biotechnology
Publisher:	Springer
Additional Information:	The copyright of this article belongs to Springer
Keywords:	Amino acids; Binding energy; Molecular dynamics; Molecular modeling; Molecules; Viruses, Binding affinities; Docking studies; Drug molecules; Molecular docking; Molecular dynamics simulations; Potential targets; Transmembrane protease; Virus infection, Diseases
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	16 Feb 2021 09:10
Last Modified:	16 Feb 2021 09:10
URI:	http://eprints.iisc.ac.in/id/eprint/67956

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