Abstract
Based on previous large-scale in silico screening several factor Xa inhibitors were proposed to potentially inhibit SARS-CoV-2 Mpro. In addition to their known anticoagulants activity this potential inhibition could have an additional therapeutic effect on patients with COVID-19 disease. In this study we examined the binding of the Apixaban, Betrixaban and Rivaroxaban to the SARS-CoV-2 Mpro with the use of the MicroScale Thermophoresis technique. Our results indicate that the experimentally measured binding affinity is weak and the therapeutic effect due to the SARS-CoV-2 Mpro inhibition is rather negligible.
MeSH terms
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Benzamides / chemistry
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Benzamides / metabolism
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Binding Sites
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COVID-19 / virology
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COVID-19 Drug Treatment
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Coronavirus M Proteins / antagonists & inhibitors*
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Coronavirus M Proteins / metabolism
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Factor Xa Inhibitors / chemistry*
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Factor Xa Inhibitors / metabolism
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Humans
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Molecular Dynamics Simulation
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Protein Binding
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Protein Stability
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Pyrazoles / chemistry
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Pyrazoles / metabolism
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Pyridines / chemistry
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Pyridines / metabolism
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Pyridones / chemistry
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Pyridones / metabolism
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Rivaroxaban / chemistry
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Rivaroxaban / metabolism
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SARS-CoV-2 / isolation & purification
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SARS-CoV-2 / metabolism*
Substances
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Benzamides
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Coronavirus M Proteins
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Factor Xa Inhibitors
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Pyrazoles
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Pyridines
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Pyridones
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membrane protein, SARS-CoV-2
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apixaban
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betrixaban
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Rivaroxaban
Grants and funding
KP, PS, PK, MB, AG - Plastic Omnium Auto Sp. z o.o. for support of the experimental part of this work. AF, MS1, MAL, MS2 - NVIDIA Corporation with the donation of a Titan Xp GPU used for this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.