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评估 Xa 抑制剂作为 SARS-CoV-2 Mpro 蛋白酶潜在抑制剂的研究。

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

机构信息

Tunneling Group, Biotechnology Centre, Silesian University of Technology, Gliwice, Poland.

Department of Pharmaceutical Sciences, Computational Pharmacy, University of Basel, Basel, Switzerland.

出版信息

PLoS One. 2022 Jan 11;17(1):e0262482. doi: 10.1371/journal.pone.0262482. eCollection 2022.

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.

摘要

基于先前的大规模计算机筛选,有几种因子 Xa 抑制剂被提出可能抑制 SARS-CoV-2 Mpro。除了它们已知的抗凝活性外,这种潜在的抑制作用可能对 COVID-19 疾病患者有额外的治疗效果。在这项研究中,我们使用微量热泳动技术研究了阿哌沙班、贝曲沙班和利伐沙班与 SARS-CoV-2 Mpro 的结合。我们的结果表明,实验测量的结合亲和力较弱,由于 SARS-CoV-2 Mpro 抑制作用产生的治疗效果相当微不足道。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a2/8752003/51aa785f8db7/pone.0262482.g001.jpg

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