Identification of Potential Molecules Against COVID-19 Main Protease Through Structure-Guided Virtual Screening Approach

Mittal, Lovika; Kumari, Anita; Srivastava, Mitul; Singh, Mrityunjay; Asthana, Shailendra

doi:10.26434/chemrxiv.12086565.v2

Cited by 5 publications

(1 citation statement)

References 11 publications

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“…Camostat mesylate, nafamostat, and leupeptin (Fig. 1) are the drugs chosen as the inhibitors of TMPRSS2, in which the drugs camostat and nafamostat are under clinical trial for COVID-19 [13,16,[18][19][20] (https://clinicaltrials.gov/ct2/show/NCT04353284) treatment, whereas leupeptin [21] is tested for its suitability against SARS-CoV-2 viral infection and also studied for its antiviral properties against SARS-CoV viruses [22,23]. To better understand the molecular binding mechanisms of these molecules, which are not completely known at the molecular dynamics level, we have computed the binding affinity, intermolecular interactions, and the stability of molecules from the molecular docking and the molecular dynamics simulations.…”

Section: Introductionmentioning

confidence: 99%

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

Kandasamy

Iruthayaraj

et al. 2021

Appl Biochem Biotechnol

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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.

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Section: Introductionmentioning

confidence: 99%

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

Kandasamy

Iruthayaraj

et al. 2021

Appl Biochem Biotechnol

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Drug Databases for Development of Therapeutics Against Coronaviruses

Kar

Leszczyński

2021

Methods in Pharmacology and Toxicology

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Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to

et al. 2020

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After the 1918 Spanish Flu pandemic caused by the H1N1 virus, the recent coronavirus disease 2019 (COVID-19) brought us to the time of serious global health catastrophe. Although no proven therapies are identified yet which can offer a definitive treatment of the COVID-19, a series of antiviral, antibacterial, antiparasitic, immunosuppressant drugs have shown clinical benefits based on repurposing theory. However, these studies are made on small number of patients, and, in majority of the cases, have been carried out as nonrandomized trials. As society is running against the time to combat the COVID-19, we present here a comprehensive review dealing with up-to-date information of therapeutics or drug regimens being utilized by physicians to treat COVID-19 patients along with in-depth discussion of mechanism of action of these drugs and their targets. Ongoing vaccine trials, monoclonal antibodies therapy and convalescent plasma treatment are also discussed. Keeping in mind that computational approaches can offer a significant insight to repurposing based drug discovery, an exhaustive discussion of computational modeling studies is performed which can assist target-specific drug discovery.

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Identification of Potential Molecules Against COVID-19 Main Protease Through Structure-Guided Virtual Screening Approach

Cited by 5 publications

References 11 publications

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

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

Drug Databases for Development of Therapeutics Against Coronaviruses

Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to

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