Evaluation of Xa inhibitors as potential inhibitors of the SARS-CoV-2 Mpro protease

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 stu...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	PloS one 2022-01, Vol.17 (1), p.e0262482-e0262482
Hauptverfasser:	Papaj, Katarzyna, Spychalska, Patrycja, Kapica, Patryk, Fischer, André, Nowak, Jakub, Bzówka, Maria, Sellner, Manuel, Lill, Markus A, Smieško, Martin, Góra, Artur
Format:	Artikel
Sprache:	eng
Schlagworte:	Anticoagulants Antiviral drugs Apixaban Benzamides - chemistry Benzamides - metabolism Binding Binding Sites Biology and life sciences Coronavirus M Proteins - antagonists & inhibitors Coronavirus M Proteins - metabolism Coronaviruses COVID-19 COVID-19 - virology COVID-19 Drug Treatment Cysteine proteinases Factor Xa Inhibitors - chemistry Factor Xa Inhibitors - metabolism Health aspects Humans Inhibitors Medicine and health sciences Molecular Dynamics Simulation Mortality Physical Sciences Physiological aspects Protein Binding Protein Stability Pyrazoles - chemistry Pyrazoles - metabolism Pyridines - chemistry Pyridines - metabolism Pyridones - chemistry Pyridones - metabolism Research and Analysis Methods Rivaroxaban Rivaroxaban - chemistry Rivaroxaban - metabolism SARS-CoV-2 - isolation & purification SARS-CoV-2 - metabolism Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Thermophoresis
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0262482