Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by massive inflammation of the arterial endothelium accompanied by vasoconstriction and widespread pulmonary micro thrombi. As a result, due to the destruction of nitric oxide (^•NO) by inflammatory superoxide (O₂^•−), pulmonary ^•NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing ^•NO by inhalation (INO) may replace the loss of endothelium-derived ^•NO. The first results from clinical trials with INO in SARS-CoV-2 patients show a rapid and sustained improvement in cardiopulmonary function and decreased inflammation. An ongoing phase III study is expected to confirm the method’s efficacy. INO may hence become a first line treatment in SARS-CoV-2 patients. However, due to the rapid inactivation of ^•NO by deoxyhemoglobin to nitrate, pulmonary administration of ^•NO will not protect remote organs. Another INO-related pharmacological approach to protect SARS-CoV-2 patients from developing life-threatening disease is to inhibit the O₂^•−-driven destruction of ^•NO by neutralizing inflammatory O₂^•−. By making use of low molecular weight compounds that mimic the action of the enzyme manganese superoxide dismutase (MnSOD). The MnSOD mimetics of the so-called porphyrin type (e.g., AEOL 10150), salen type (e.g., EUK-8) and cyclic polyamine type (e.g., M40419, today known as GC4419 and avasopasem manganese) have all been shown to positively affect the inflammatory response in lung epithelial cells in preclinical models of chronic obstructive pulmonary disease. The Manganese diPyridoxyL EthylDiamine (MnPLED)-type mangafodipir (manganese dipyridoxyl diphosphate—MnDPDP), a magnetic resonance imaging (MRI) contrast agent that possesses MnSOD mimetic activity, has shown promising results in various forms of inflammation, in preclinical as well as clinical settings. Intravenously administration of mangafodipir will, in contrast to INO, reach remote organs and may hence become an important supplement to INO. From the authors’ viewpoint, it appears logical to test mangafodipr in COVID-19 patients at risk of developing life-threatening SARS-CoV-2. Five days after submission of the current manuscript, Galera Pharmaceuticals Inc. announced the dosing of the first patient in a randomized, double-blind pilot phase II clinical trial with GC4419 for COVID-19. The study was first posted on ClinicalTrials.gov (Identifier: NCT04555096) 18 September 2020.

中文翻译：

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Mangafodipir或其他SOD模拟药物是否可以为COVID-19患者提供更好的护理？

严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）的特征是动脉内皮大量发炎，伴有血管收缩和广泛的肺微血栓。结果，由于炎性超氧化物（O ₂ ^•−）破坏了一氧化氮（^• NO），肺^• NO浓度停止，导致不受控制的血小板凝集和大量血栓形成，从而杀死了患者。引入^•吸入NO（INO）可以替代源自内皮的损失^•没有。INO在SARS-CoV-2患者中进行的临床试验的第一批结果显示，心肺功能迅速且持续改善，炎症减少。正在进行的III期研究有望确认该方法的有效性。因此，INO可能成为SARS-CoV-2患者的一线治疗。然而，由于迅速失活^• NO由脱氧血红蛋白硝酸盐的肺部给药^• NO不会保护远程器官。保护SARS-COV-2患者制定危及生命的疾病的另一个INO相关的药理学方法是抑制Ø ₂ ^{• -}驱动的破坏^•通过中和炎性O否₂ ^{• -}。通过使用模仿锰超氧化物歧化酶（MnSOD）酶作用的低分子量化合物。事实证明，所谓的卟啉型（例如AEOL 10150），sallen型（例如EUK-8）和环状多胺型（例如M40419，今天称为GC4419和阿vasopasem锰）的MnSOD模拟物均具有积极作用。慢性阻塞性肺疾病的临床前模型中肺上皮细胞的炎症反应 锰二吡啶氧基乙二胺（MnPLED）型mangafodipir（锰二吡啶氧基二磷酸锰-MnDPDP）是一种具有MnSOD模拟活性的磁共振成像（MRI）造影剂，已在临床前和临床环境中以各种形式的炎症显示出令人鼓舞的结果。与INO相比，静脉注射Mangafodipir会 到达遥远的器官，因此可能成为INO的重要补充。从作者的角度来看，在有发展为威胁生命的SARS-CoV-2风险的COVID-19患者中测试mangafodipr似乎合乎逻辑。在提交当前手稿五天后，Galera Pharmaceuticals Inc.宣布在随机，双盲II期临床试验的第一例患者中使用GC4419进行COVID-19的给药。该研究首次发布于2020年9月18日在ClinicalTrials.gov（标识符：NCT04555096）上。GC4419用于COVID-19的双盲中试II期临床试验。该研究首次发布于2020年9月18日在ClinicalTrials.gov（标识符：NCT04555096）上。GC4419用于COVID-19的双盲中试II期临床试验。该研究首次发布于2020年9月18日在ClinicalTrials.gov（标识符：NCT04555096）上。