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气态一氧化氮和含硫醇配体的二亚硝酰基铁配合物作为可缓解新冠病毒病的潜在药物

Gaseous Nitric Oxide and Dinitrosyl Iron Complexes with Thiol-Containing Ligands as Potential Medicines that Can Relieve COVID-19.

作者信息

Vanin A F, Pekshev A V, Vagapov A B, Sharapov N A, Lakomkin V L, Abramov A A, Timoshin A A, Kapelko V I

机构信息

Semenov Federal Research Center of Chemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia.

Institute of Regenerative Medicine, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, 119991 Moscow, Russia.

出版信息

Biophysics (Oxf). 2021;66(1):155-163. doi: 10.1134/S0006350921010218. Epub 2021 Apr 27.

DOI:10.1134/S0006350921010218
PMID:33935291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8078388/
Abstract

It is shown that the inhalation of gaseous nitric oxide (gNO) or sprayed aqueous solutions of binuclear dinitrosyl iron complexes with glutathione or -acetyl-L-cysteine by animals or humans provokes no perceptible hypotensive effects. Potentially, these procedures may be useful in COVID-19 treatment. The NO level in complexes with hemoglobin in blood decreases as the gNO concentration in the gas flow produced by the Plazon system increases from 100 to 2100 ppm, so that at 2000 ppm more than one-half of the gas can be incorporated into dinitrosyl complexes formed in tissues of the lungs and respiratory tract. Thus, the effect of gNO inhalation may be similar to that observed after administration of solutions of dinitrosyl iron complexes, namely, to the presence of dinitrosyl iron complexes with thiol-containing ligands in lung and airway tissues. With regard to the hypothesis posited earlier that these complexes can suppress coronavirus replication as donors of nitrosonium cations (Biophysics 65, 818, 2020), it is not inconceivable that administration of gNO or chemically synthesized dinitrosyl iron complexes with thiol-containing ligands may help treat COVID-19. In tests on the authors of this paper as volunteers, the tolerance concentration of gNO inhaled within 15 min was approximately 2000 ppm. In tests on rats that inhaled sprayed aqueous solutions of dinitrosyl iron complexes, their tolerance dose was approximately 0.4 mmol/kg body weight.

摘要

研究表明,动物或人类吸入气态一氧化氮(gNO)或喷有双核二亚硝酰基铁配合物与谷胱甘肽或N - 乙酰 - L - 半胱氨酸的水溶液不会引发明显的降压作用。这些方法可能对COVID - 19治疗有用。随着Plazon系统产生的气流中gNO浓度从100 ppm增加到2100 ppm,血液中与血红蛋白结合的配合物中的NO水平降低,因此在2000 ppm时,超过一半的气体可结合到肺和呼吸道组织中形成的二亚硝酰基配合物中。因此,吸入gNO的效果可能与给予二亚硝酰基铁配合物溶液后观察到的效果相似,即在肺和气道组织中存在含有硫醇配体的二亚硝酰基铁配合物。关于之前提出的这些配合物可作为亚硝鎓阳离子供体抑制冠状病毒复制的假设(《生物物理学》65, 818, 2020),吸入gNO或化学合成的含有硫醇配体的二亚硝酰基铁配合物可能有助于治疗COVID - 19并非不可想象。在以本文作者为志愿者的测试中,15分钟内吸入gNO的耐受浓度约为2000 ppm。在对吸入喷有二亚硝酰基铁配合物水溶液的大鼠进行的测试中,它们的耐受剂量约为0.4 mmol/kg体重。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6877/8078388/423bd484a8f5/11439_2021_9367_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6877/8078388/5d7a2c1293b9/11439_2021_9367_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6877/8078388/423bd484a8f5/11439_2021_9367_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6877/8078388/5d7a2c1293b9/11439_2021_9367_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6877/8078388/5d2009bea4ee/11439_2021_9367_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6877/8078388/286ee626872f/11439_2021_9367_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6877/8078388/dbfa4f87dc3c/11439_2021_9367_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6877/8078388/423bd484a8f5/11439_2021_9367_Fig6_HTML.jpg

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