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Article ; Online: Clinical implications of vitamin B

Offringa, Annette K / Bourgonje, Arno R / Schrier, Matthew S / Deth, Richard C / van Goor, Harry

2021 Volume 27, Issue 10, Page(s) 931–934

Abstract: ... Vitamin ... ...

Abstract	Vitamin B
MeSH term(s)	Cobalt ; Humans ; Methylmalonyl-CoA Mutase/genetics ; Methylmalonyl-CoA Mutase/metabolism ; Oxidation-Reduction ; Vitamin B 12/metabolism ; Vitamin B 12/pharmacology ; Vitamins
Chemical Substances	Vitamins ; Cobalt (3G0H8C9362) ; Methylmalonyl-CoA Mutase (EC 5.4.99.2) ; Vitamin B 12 (P6YC3EG204)
Language	English
Publishing date	2021-07-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2021.07.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 4345: Show issues

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Article: The Disease-Modifying Role of Taurine and Its Therapeutic Potential in Coronavirus Disease 2019 (COVID-19).

van Eijk, Larissa E / Offringa, Annette K / Bernal, Maria-Elena / Bourgonje, Arno R / van Goor, Harry / Hillebrands, Jan-Luuk

Advances in experimental medicine and biology

2022 Volume 1370, Page(s) 3–21

Abstract: Taurine is an amino sulfonic acid that is implicated in numerous physiological functions, including the regulation of oxidative stress, which plays an important role in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome ... ...

Abstract	Taurine is an amino sulfonic acid that is implicated in numerous physiological functions, including the regulation of oxidative stress, which plays an important role in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), together with other pathophysiological processes. The recent finding of decreased serum taurine levels in SARS-CoV-2-infected patients, in tandem with its potential modulatory role in COVID-19 due to its antiviral, antioxidant, anti-inflammatory, and vascular-related effects, provides a rationale for considering taurine as a beneficial supplement in patients suffering from COVID-19. Here, we reviewed the potential disease-modifying effects of taurine and combined these with the current knowledge on COVID-19 to clarify the potential role of taurine in this respiratory disease.
MeSH term(s)	Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Humans ; SARS-CoV-2 ; Taurine/pharmacology ; Taurine/therapeutic use
Chemical Substances	Antiviral Agents ; Taurine (1EQV5MLY3D)
Language	English
Publishing date	2022-07-26
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-030-93337-1_1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The mechanistic overview of SARS-CoV-2 using angiotensin-converting enzyme 2 to enter the cell for replication: possible treatment options related to the renin-angiotensin system.

Offringa, Annette / Montijn, Roy / Singh, Sandeep / Paul, Martin / Pinto, Yigal M / Pinto-Sietsma, Sara-Joan

European heart journal. Cardiovascular pharmacotherapy

2020 Volume 6, Issue 5, Page(s) 317–325

Abstract: The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made ... ...

Abstract	The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the mechanisms of SARS-CoV-2 infection and host responses, which is coupled to the practical experience of clinicians that are treating patients. Because SARS-CoV-2 enters the cell by binding to angiotensin-converting enzyme 2 (ACE2), targeting ACE2 to prevent such binding seems an obvious strategy to combat infection. However, ACE2 performs its functions outside the cell and was found to enter the cell only by angiotensin II type 1 receptor (AT1R)-induced endocytosis, after which ACE2 is destroyed. This means that preventing uptake of ACE2 into the cell by blocking AT1R would be a more logical approach to limit entry of SARS-CoV-2 into the cell. Since ACE2 plays an important protective role in maintaining key biological processes, treatments should not disrupt the functional capacity of ACE2, to counterbalance the negative effects of the infection. Based on known mechanisms and knowledge of the characteristics of SARS-CoV we propose the hypothesis that the immune system facilitates SARS-CoV-2 replication which disrupts immune regulatory mechanisms. The proposed mechanism by which SARS-CoV-2 causes disease immediately suggests a possible treatment, since the AT1R is a key player in this whole process. AT1R antagonists appear to be the ideal candidate for the treatment of SARS-CoV-2 infection. AT1R antagonists counterbalance the negative consequences of angiotesnin II and, in addition, they might even be involved in preventing the cellular uptake of the virus without interfering with ACE2 function. AT1R antagonists are widely available, cheap, and safe. Therefore, we propose to consider using AT1R antagonists in the treatment of SARS-CoV-2.
MeSH term(s)	Angiotensin II/metabolism ; Angiotensin II Type 1 Receptor Blockers/therapeutic use ; Animals ; Antiviral Agents/therapeutic use ; Betacoronavirus/drug effects ; Betacoronavirus/immunology ; Betacoronavirus/pathogenicity ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/metabolism ; Coronavirus Infections/virology ; Endocytosis/drug effects ; Host-Pathogen Interactions ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Peptidyl-Dipeptidase A/therapeutic use ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/virology ; Renin-Angiotensin System/drug effects ; SARS-CoV-2 ; Virus Internalization/drug effects ; COVID-19 Drug Treatment
Chemical Substances	Angiotensin II Type 1 Receptor Blockers ; Antiviral Agents ; Angiotensin II (11128-99-7) ; ACE protein, human (EC 3.4.15.1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Keywords	covid19
Language	English
Publishing date	2020-05-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2808613-2
ISSN	2055-6845 ; 2055-6837
ISSN (online)	2055-6845
ISSN	2055-6837
DOI	10.1093/ehjcvp/pvaa053
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The mechanistic overview of SARS-CoV-2 using angiotensin-converting enzyme 2 to enter the cell for replication

Offringa, Annette / Montijn, Roy / Singh, Sandeep / Paul, Martin / Pinto, Yigal M / Pinto-Sietsma*, Sara-Joan

European Heart Journal - Cardiovascular Pharmacotherapy

possible treatment options related to the renin–angiotensin system

2020 Volume 6, Issue 5, Page(s) 317–325

Abstract: Abstract The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be ... ...

Abstract	Abstract The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the mechanisms of SARS-CoV-2 infection and host responses, which is coupled to the practical experience of clinicians that are treating patients. Because SARS-CoV-2 enters the cell by binding to angiotensin-converting enzyme 2 (ACE2), targeting ACE2 to prevent such binding seems an obvious strategy to combat infection. However, ACE2 performs its functions outside the cell and was found to enter the cell only by angiotensin II type 1 receptor (AT1R)-induced endocytosis, after which ACE2 is destroyed. This means that preventing uptake of ACE2 into the cell by blocking AT1R would be a more logical approach to limit entry of SARS-CoV-2 into the cell. Since ACE2 plays an important protective role in maintaining key biological processes, treatments should not disrupt the functional capacity of ACE2, to counterbalance the negative effects of the infection. Based on known mechanisms and knowledge of the characteristics of SARS-CoV we propose the hypothesis that the immune system facilitates SARS-CoV-2 replication which disrupts immune regulatory mechanisms. The proposed mechanism by which SARS-CoV-2 causes disease immediately suggests a possible treatment, since the AT1R is a key player in this whole process. AT1R antagonists appear to be the ideal candidate for the treatment of SARS-CoV-2 infection. AT1R antagonists counterbalance the negative consequences of angiotesnin II and, in addition, they might even be involved in preventing the cellular uptake of the virus without interfering with ACE2 function. AT1R antagonists are widely available, cheap, and safe. Therefore, we propose to consider using AT1R antagonists in the treatment of SARS-CoV-2.
Keywords	covid19
Language	English
Publisher	Oxford University Press (OUP)
Publishing country	uk
Document type	Article ; Online
ZDB-ID	2808613-2
ISSN	2055-6845 ; 2055-6837
ISSN (online)	2055-6845
ISSN	2055-6837
DOI	10.1093/ehjcvp/pvaa053
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The mechanistic overview of SARS-CoV-2 using angiotensin-converting enzyme 2 to enter the cell for replication: possible treatment options related to the renin-angiotensin system

Offringa, Annette / Montijn, Roy / Singh, Sandeep / Paul, Martin / Pinto, Yigal M / Pinto-Sietsma, Sara-Joan

Eur Heart J Cardiovasc Pharmacother

Abstract	The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the mechanisms of SARS-CoV-2 infection and host responses, which is coupled to the practical experience of clinicians that are treating patients. Because SARS-CoV-2 enters the cell by binding to angiotensin-converting enzyme 2 (ACE2), targeting ACE2 to prevent such binding seems an obvious strategy to combat infection. However, ACE2 performs its functions outside the cell and was found to enter the cell only by angiotensin II type 1 receptor (AT1R)-induced endocytosis, after which ACE2 is destroyed. This means that preventing uptake of ACE2 into the cell by blocking AT1R would be a more logical approach to limit entry of SARS-CoV-2 into the cell. Since ACE2 plays an important protective role in maintaining key biological processes, treatments should not disrupt the functional capacity of ACE2, to counterbalance the negative effects of the infection. Based on known mechanisms and knowledge of the characteristics of SARS-CoV we propose the hypothesis that the immune system facilitates SARS-CoV-2 replication which disrupts immune regulatory mechanisms. The proposed mechanism by which SARS-CoV-2 causes disease immediately suggests a possible treatment, since the AT1R is a key player in this whole process. AT1R antagonists appear to be the ideal candidate for the treatment of SARS-CoV-2 infection. AT1R antagonists counterbalance the negative consequences of angiotesnin II and, in addition, they might even be involved in preventing the cellular uptake of the virus without interfering with ACE2 function. AT1R antagonists are widely available, cheap, and safe. Therefore, we propose to consider using AT1R antagonists in the treatment of SARS-CoV-2.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #401349
Database	COVID19

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Article ; Online: N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019.

Bourgonje, Arno R / Offringa, Annette K / van Eijk, Larissa E / Abdulle, Amaal E / Hillebrands, Jan-Luuk / van der Voort, Peter H J / van Goor, Harry / van Hezik, Ed J

Antioxidants & redox signaling

2021 Volume 35, Issue 14, Page(s) 1207–1225

Abstract: Significance: ...

Abstract	Significance:
MeSH term(s)	Acetylcysteine/metabolism ; COVID-19/metabolism ; Humans ; Hydrogen Sulfide/metabolism ; Oxidation-Reduction
Chemical Substances	Acetylcysteine (WYQ7N0BPYC) ; Hydrogen Sulfide (YY9FVM7NSN)
Language	English
Publishing date	2021-03-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2020.8247
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Zs.A 5488: Show issues

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Article ; Online: COVID-19: immunopathology, pathophysiological mechanisms, and treatment options.

van Eijk, Larissa E / Binkhorst, Mathijs / Bourgonje, Arno R / Offringa, Annette K / Mulder, Douwe J / Bos, Eelke M / Kolundzic, Nikola / Abdulle, Amaal E / van der Voort, Peter Hj / Olde Rikkert, Marcel Gm / van der Hoeven, Johannes G / den Dunnen, Wilfred Fa / Hillebrands, Jan-Luuk / van Goor, Harry

The Journal of pathology

2021 Volume 254, Issue 4, Page(s) 307–331

Abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID-19 cases are ... ...

Abstract	Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID-19 cases are characterised by a mild, self-limiting disease course, a considerable subset of patients develop a more severe condition, varying from pneumonia and acute respiratory distress syndrome (ARDS) to multi-organ failure (MOF). Progression of COVID-19 is thought to occur as a result of a complex interplay between multiple pathophysiological mechanisms, all of which may orchestrate SARS-CoV-2 infection and contribute to organ-specific tissue damage. In this respect, dissecting currently available knowledge of COVID-19 immunopathogenesis is crucially important, not only to improve our understanding of its pathophysiology but also to fuel the rationale of both novel and repurposed treatment modalities. Various immune-mediated pathways during SARS-CoV-2 infection are relevant in this context, which relate to innate immunity, adaptive immunity, and autoimmunity. Pathological findings in tissue specimens of patients with COVID-19 provide valuable information with regard to our understanding of pathophysiology as well as the development of evidence-based treatment regimens. This review provides an updated overview of the main pathological changes observed in COVID-19 within the most commonly affected organ systems, with special emphasis on immunopathology. Current management strategies for COVID-19 include supportive care and the use of repurposed or symptomatic drugs, such as dexamethasone, remdesivir, and anticoagulants. Ultimately, prevention is key to combat COVID-19, and this requires appropriate measures to attenuate its spread and, above all, the development and implementation of effective vaccines. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
MeSH term(s)	Adaptive Immunity/drug effects ; Adaptive Immunity/immunology ; Antiviral Agents/pharmacology ; COVID-19/pathology ; COVID-19/virology ; Humans ; Immunity, Innate/drug effects ; Immunity, Innate/immunology ; SARS-CoV-2/pathogenicity ; United Kingdom ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2021-03-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.5642
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Article: COVID‐19: immunopathology, pathophysiological mechanisms, and treatment options

van Eijk, Larissa / Binkhorst, Mathijs / Bourgonje, Arno / Offringa, Annette / Mulder, Douwe / Bos, Eelke / Kolundzic, Nikola / Eman Abdulle, Amaal / van der Voort, Peter HJ / Olde Rikkert, Marcel / van der Hoeven, Johannes G. / den Dunnen, Wilfred / Hillebrands, Jan-Luuk / van Goor, Harry

Early View

2021

Abstract: Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID‐19 cases are ... ...

Abstract	Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID‐19 cases are characterised by a mild, self‐limiting disease course, a considerable subset of patients develop a more severe condition, varying from pneumonia and acute respiratory distress syndrome (ARDS) to multi‐organ failure (MOF). Progression of COVID‐19 is thought to occur as a result of a complex interplay between multiple pathophysiological mechanisms, all of which may orchestrate SARS‐CoV‐2 infection and contribute to organ‐specific tissue damage. In this respect, dissecting currently available knowledge of COVID‐19 immunopathogenesis is crucially important, not only to improve our understanding of its pathophysiology but also to fuel the rationale of both novel and repurposed treatment modalities. Various immune‐mediated pathways during SARS‐CoV‐2 infection are relevant in this context, which relate to innate immunity, adaptive immunity, and autoimmunity. Pathological findings in tissue specimens of patients with COVID‐19 provide valuable information with regard to our understanding of pathophysiology as well as the development of evidence‐based treatment regimens. This review provides an updated overview of the main pathological changes observed in COVID‐19 within the most commonly affected organ systems, with special emphasis on immunopathology. Current management strategies for COVID‐19 include supportive care and the use of repurposed or symptomatic drugs, such as dexamethasone, remdesivir, and anticoagulants. Ultimately, prevention is key to combat COVID‐19, and this requires appropriate measures to attenuate its spread and, above all, the development and implementation of effective vaccines. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Keywords	COVID-19 ; coronavirus disease 2019 (COVID-19) ; angiotensin-converting enzyme 2 (ACE2) ; acute respiratory distress syndrome (ARDS) ; autoimmunity ; diffuse alveolar damage (DAD) ; immunopathology ; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ; pathology ; pathophysiology ; treatment
Language	English
Document type	Article
Database	Repository for Life Sciences

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