May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients?

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 (<sup<•</sup<NO) by inflammatory superoxide (O<sub<2</sub<<sup<•−</sup<), pulmonary <sup<•</sup<NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing <sup<•</sup<NO by inhalation (INO) may replace the loss of endothelium-derived <sup<•</sup<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 <sup<•</sup<NO by deoxyhemoglobin to nitrate, pulmonary administration of <sup<•</sup<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 O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Jan Olof G Karlsson [verfasserIn] Per Jynge [verfasserIn] Louis J Ignarro [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	mangafodipir inflammation SARS-CoV-2 COVID-19 MnSOD-mimetic nitric oxide

Übergeordnetes Werk:	In: Antioxidants - MDPI AG, 2013, 9(2020), 10, p 971
Übergeordnetes Werk:	volume:9 ; year:2020 ; number:10, p 971

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/antiox9100971

Katalog-ID:	DOAJ043708501

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allfields	10.3390/antiox9100971 doi (DE-627)DOAJ043708501 (DE-599)DOAJ160b12882ad54a7fa2fab6c22ad66b73 DE-627 ger DE-627 rakwb eng RM1-950 Jan Olof G Karlsson verfasserin aut May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients? 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (<sup<•</sup<NO) by inflammatory superoxide (O<sub<2</sub<<sup<•−</sup<), pulmonary <sup<•</sup<NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing <sup<•</sup<NO by inhalation (INO) may replace the loss of endothelium-derived <sup<•</sup<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 <sup<•</sup<NO by deoxyhemoglobin to nitrate, pulmonary administration of <sup<•</sup<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 O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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. mangafodipir inflammation SARS-CoV-2 COVID-19 MnSOD-mimetic nitric oxide Therapeutics. Pharmacology Per Jynge verfasserin aut Louis J Ignarro verfasserin aut In Antioxidants MDPI AG, 2013 9(2020), 10, p 971 (DE-627)737287578 (DE-600)2704216-9 20763921 nnns volume:9 year:2020 number:10, p 971 https://doi.org/10.3390/antiox9100971 kostenfrei https://doaj.org/article/160b12882ad54a7fa2fab6c22ad66b73 kostenfrei https://www.mdpi.com/2076-3921/9/10/971 kostenfrei https://doaj.org/toc/2076-3921 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 10, p 971
spelling	10.3390/antiox9100971 doi (DE-627)DOAJ043708501 (DE-599)DOAJ160b12882ad54a7fa2fab6c22ad66b73 DE-627 ger DE-627 rakwb eng RM1-950 Jan Olof G Karlsson verfasserin aut May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients? 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (<sup<•</sup<NO) by inflammatory superoxide (O<sub<2</sub<<sup<•−</sup<), pulmonary <sup<•</sup<NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing <sup<•</sup<NO by inhalation (INO) may replace the loss of endothelium-derived <sup<•</sup<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 <sup<•</sup<NO by deoxyhemoglobin to nitrate, pulmonary administration of <sup<•</sup<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 O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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. mangafodipir inflammation SARS-CoV-2 COVID-19 MnSOD-mimetic nitric oxide Therapeutics. Pharmacology Per Jynge verfasserin aut Louis J Ignarro verfasserin aut In Antioxidants MDPI AG, 2013 9(2020), 10, p 971 (DE-627)737287578 (DE-600)2704216-9 20763921 nnns volume:9 year:2020 number:10, p 971 https://doi.org/10.3390/antiox9100971 kostenfrei https://doaj.org/article/160b12882ad54a7fa2fab6c22ad66b73 kostenfrei https://www.mdpi.com/2076-3921/9/10/971 kostenfrei https://doaj.org/toc/2076-3921 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 10, p 971
allfields_unstemmed	10.3390/antiox9100971 doi (DE-627)DOAJ043708501 (DE-599)DOAJ160b12882ad54a7fa2fab6c22ad66b73 DE-627 ger DE-627 rakwb eng RM1-950 Jan Olof G Karlsson verfasserin aut May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients? 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (<sup<•</sup<NO) by inflammatory superoxide (O<sub<2</sub<<sup<•−</sup<), pulmonary <sup<•</sup<NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing <sup<•</sup<NO by inhalation (INO) may replace the loss of endothelium-derived <sup<•</sup<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 <sup<•</sup<NO by deoxyhemoglobin to nitrate, pulmonary administration of <sup<•</sup<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 O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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. mangafodipir inflammation SARS-CoV-2 COVID-19 MnSOD-mimetic nitric oxide Therapeutics. Pharmacology Per Jynge verfasserin aut Louis J Ignarro verfasserin aut In Antioxidants MDPI AG, 2013 9(2020), 10, p 971 (DE-627)737287578 (DE-600)2704216-9 20763921 nnns volume:9 year:2020 number:10, p 971 https://doi.org/10.3390/antiox9100971 kostenfrei https://doaj.org/article/160b12882ad54a7fa2fab6c22ad66b73 kostenfrei https://www.mdpi.com/2076-3921/9/10/971 kostenfrei https://doaj.org/toc/2076-3921 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 10, p 971
allfieldsGer	10.3390/antiox9100971 doi (DE-627)DOAJ043708501 (DE-599)DOAJ160b12882ad54a7fa2fab6c22ad66b73 DE-627 ger DE-627 rakwb eng RM1-950 Jan Olof G Karlsson verfasserin aut May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients? 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (<sup<•</sup<NO) by inflammatory superoxide (O<sub<2</sub<<sup<•−</sup<), pulmonary <sup<•</sup<NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing <sup<•</sup<NO by inhalation (INO) may replace the loss of endothelium-derived <sup<•</sup<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 <sup<•</sup<NO by deoxyhemoglobin to nitrate, pulmonary administration of <sup<•</sup<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 O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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. mangafodipir inflammation SARS-CoV-2 COVID-19 MnSOD-mimetic nitric oxide Therapeutics. Pharmacology Per Jynge verfasserin aut Louis J Ignarro verfasserin aut In Antioxidants MDPI AG, 2013 9(2020), 10, p 971 (DE-627)737287578 (DE-600)2704216-9 20763921 nnns volume:9 year:2020 number:10, p 971 https://doi.org/10.3390/antiox9100971 kostenfrei https://doaj.org/article/160b12882ad54a7fa2fab6c22ad66b73 kostenfrei https://www.mdpi.com/2076-3921/9/10/971 kostenfrei https://doaj.org/toc/2076-3921 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 10, p 971
allfieldsSound	10.3390/antiox9100971 doi (DE-627)DOAJ043708501 (DE-599)DOAJ160b12882ad54a7fa2fab6c22ad66b73 DE-627 ger DE-627 rakwb eng RM1-950 Jan Olof G Karlsson verfasserin aut May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients? 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 (<sup<•</sup<NO) by inflammatory superoxide (O<sub<2</sub<<sup<•−</sup<), pulmonary <sup<•</sup<NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing <sup<•</sup<NO by inhalation (INO) may replace the loss of endothelium-derived <sup<•</sup<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 <sup<•</sup<NO by deoxyhemoglobin to nitrate, pulmonary administration of <sup<•</sup<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 O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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. mangafodipir inflammation SARS-CoV-2 COVID-19 MnSOD-mimetic nitric oxide Therapeutics. Pharmacology Per Jynge verfasserin aut Louis J Ignarro verfasserin aut In Antioxidants MDPI AG, 2013 9(2020), 10, p 971 (DE-627)737287578 (DE-600)2704216-9 20763921 nnns volume:9 year:2020 number:10, p 971 https://doi.org/10.3390/antiox9100971 kostenfrei https://doaj.org/article/160b12882ad54a7fa2fab6c22ad66b73 kostenfrei https://www.mdpi.com/2076-3921/9/10/971 kostenfrei https://doaj.org/toc/2076-3921 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 10, p 971
language	English
source	In Antioxidants 9(2020), 10, p 971 volume:9 year:2020 number:10, p 971
sourceStr	In Antioxidants 9(2020), 10, p 971 volume:9 year:2020 number:10, p 971
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	mangafodipir inflammation SARS-CoV-2 COVID-19 MnSOD-mimetic nitric oxide Therapeutics. Pharmacology
isfreeaccess_bool	true
container_title	Antioxidants
authorswithroles_txt_mv	Jan Olof G Karlsson @@aut@@ Per Jynge @@aut@@ Louis J Ignarro @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	737287578
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language_de	englisch
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Another INO-related pharmacological approach to protect SARS-CoV-2 patients from developing life-threatening disease is to inhibit the O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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. 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spellingShingle	Jan Olof G Karlsson misc RM1-950 misc mangafodipir misc inflammation misc SARS-CoV-2 misc COVID-19 misc MnSOD-mimetic misc nitric oxide misc Therapeutics. Pharmacology May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients?
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topic	misc RM1-950 misc mangafodipir misc inflammation misc SARS-CoV-2 misc COVID-19 misc MnSOD-mimetic misc nitric oxide misc Therapeutics. Pharmacology
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title	May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients?
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title_sort	may mangafodipir or other sod mimetics contribute to better care in covid-19 patients?
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title_auth	May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients?
abstract	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 (<sup<•</sup<NO) by inflammatory superoxide (O<sub<2</sub<<sup<•−</sup<), pulmonary <sup<•</sup<NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing <sup<•</sup<NO by inhalation (INO) may replace the loss of endothelium-derived <sup<•</sup<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 <sup<•</sup<NO by deoxyhemoglobin to nitrate, pulmonary administration of <sup<•</sup<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 O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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.
abstractGer	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 (<sup<•</sup<NO) by inflammatory superoxide (O<sub<2</sub<<sup<•−</sup<), pulmonary <sup<•</sup<NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing <sup<•</sup<NO by inhalation (INO) may replace the loss of endothelium-derived <sup<•</sup<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 <sup<•</sup<NO by deoxyhemoglobin to nitrate, pulmonary administration of <sup<•</sup<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 O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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.
abstract_unstemmed	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 (<sup<•</sup<NO) by inflammatory superoxide (O<sub<2</sub<<sup<•−</sup<), pulmonary <sup<•</sup<NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing <sup<•</sup<NO by inhalation (INO) may replace the loss of endothelium-derived <sup<•</sup<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 <sup<•</sup<NO by deoxyhemoglobin to nitrate, pulmonary administration of <sup<•</sup<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 O<sub<2</sub<<sup<•−</sup<-driven destruction of <sup<•</sup<NO by neutralizing inflammatory O<sub<2</sub<<sup<•−</sup<. 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.
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