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Article ; Online: Anticonvulsant effects of sertraline: a case report.

Brennecke, Anja / Weaver, Donald F

2020 Volume 80, Page(s) 1–2

MeSH term(s)	Adult ; Anticonvulsants/adverse effects ; Depression/drug therapy ; Epilepsy/drug therapy ; Female ; Humans ; Serotonin Uptake Inhibitors/adverse effects ; Sertraline/adverse effects ; Sertraline/therapeutic use ; Treatment Outcome
Chemical Substances	Anticonvulsants ; Serotonin Uptake Inhibitors ; Sertraline (QUC7NX6WMB)
Language	English
Publishing date	2020-05-22
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	1137610-7
ISSN	1532-2688 ; 1059-1311
ISSN (online)	1532-2688
ISSN	1059-1311
DOI	10.1016/j.seizure.2020.05.016
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Arztbewertungsportal: Das Portal Jameda muss nach einem Urteil des Bundesgerichtshofs ein Arztprofil löschen, weil die gelisteten Arzte ungleich dargestellt wurden

Brennecke, Carsten / Wilkat, Anja

Deutsches Ärzteblatt : Ausgabe A, Praxis-Ausgabe : niedergelassene Ärzte

2018 Volume 115, Issue 9, Page(s) 372

Language	German
Document type	Article
ZDB-ID	1453475-7
ISSN	0012-1207
Database	Current Contents Medicine

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Article ; Online: Is Inhaled Furosemide a Potential Therapeutic for COVID-19?

Brennecke, Anja / Villar, Laura / Wang, Zhiyu / Doyle, Lisa M / Meek, Autumn / Reed, Mark / Barden, Christopher / Weaver, Donald F

The American journal of the medical sciences

2020 Volume 360, Issue 3, Page(s) 216–221

Abstract: The potentially lethal infection caused by the novel Severe Acute Respiratory Disease Coronavirus-2 (SARS-CoV-2) has evolved into a global crisis. Following the initial viral infection is the host inflammatory response that frequently results in ... ...

Abstract	The potentially lethal infection caused by the novel Severe Acute Respiratory Disease Coronavirus-2 (SARS-CoV-2) has evolved into a global crisis. Following the initial viral infection is the host inflammatory response that frequently results in excessive secretion of inflammatory cytokines (e.g., IL-6 and TNFα), developing into a self-targeting, toxic "cytokine storm" causing critical pulmonary tissue damage. The need for a therapeutic that is available immediately is growing daily but the de novo development of a vaccine may take years. Therefore, repurposing of approved drugs offers a promising approach to address this urgent need. Inhaled furosemide, a small molecule capable of inhibiting IL-6 and TNFα, may be an agent capable of treating the Coronavirus Disease 2019 cytokine storm in both resource-rich and developing countries. Furosemide is a "repurpose-able" small molecule therapeutics, that is safe, easily synthesized, handled, and stored, and is available in reasonable quantities worldwide.
MeSH term(s)	Administration, Inhalation ; Antiviral Agents/administration & dosage ; Antiviral Agents/pharmacokinetics ; Betacoronavirus/drug effects ; Betacoronavirus/immunology ; Betacoronavirus/metabolism ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/metabolism ; Furosemide/administration & dosage ; Furosemide/pharmacokinetics ; Humans ; Immunity, Innate/drug effects ; Immunity, Innate/physiology ; Inflammation Mediators/antagonists & inhibitors ; Inflammation Mediators/immunology ; Inflammation Mediators/metabolism ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Pneumonia, Viral/metabolism ; SARS-CoV-2 ; Sodium Potassium Chloride Symporter Inhibitors/administration & dosage ; Sodium Potassium Chloride Symporter Inhibitors/pharmacokinetics
Chemical Substances	Antiviral Agents ; Inflammation Mediators ; Sodium Potassium Chloride Symporter Inhibitors ; Furosemide (7LXU5N7ZO5)
Keywords	covid19
Language	English
Publishing date	2020-06-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	82078-7
ISSN	1538-2990 ; 0002-9629
ISSN (online)	1538-2990
ISSN	0002-9629
DOI	10.1016/j.amjms.2020.05.044
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Article ; Online: Is Inhaled Furosemide a Potential Therapeutic for COVID-19?

Brennecke, Anja / Villar, Laura / Wang, Zhiyu / Doyle, Lisa M. / Meek, Autumn / Reed, Mark / Barden, Christopher / Weaver, Donald F.

The American Journal of the Medical Sciences

2020 Volume 360, Issue 3, Page(s) 216–221

Keywords	General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	82078-7
ISSN	1538-2990 ; 0002-9629
ISSN (online)	1538-2990
ISSN	0002-9629
DOI	10.1016/j.amjms.2020.05.044
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide.

Wang, Zhiyu / Wang, Yanfei / Vilekar, Prachi / Yang, Seung-Pil / Gupta, Mayuri / Oh, Myong In / Meek, Autumn / Doyle, Lisa / Villar, Laura / Brennecke, Anja / Liyanage, Imindu / Reed, Mark / Barden, Christopher / Weaver, Donald F

PeerJ

2020 Volume 8, Page(s) e9533

Abstract: The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may ...

Abstract	The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia ("cytokine storm"). To address this immuno-inflammatory pathogenesis, multiple clinical trials have been proposed to evaluate anti-inflammatory biologic therapies targeting specific cytokines. However, despite the obvious clinical utility of such biologics, their specific applicability to COVID-19 has multiple drawbacks, including they target only one of the multiple cytokines involved in COVID-19's immunopathy. Therefore, we set out to identify a small molecule with broad-spectrum anti-inflammatory mechanism of action targeting multiple cytokines of innate immunity. In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. This has enabled us to identify the loop diuretic furosemide as a candidate molecule. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Upon treatment with furosemide, LPS-induced production of pro-inflammatory cytokines was reduced, indicating that furosemide suppresses the M1 polarization, including IL-6 and TNF-α release. In addition, we found that furosemide promotes the production of anti-inflammatory cytokine products (IL-1RA, arginase), indicating M2 polarization. Accordingly, we conclude that furosemide is a reasonably potent inhibitor of IL-6 and TNF-α that is also safe, inexpensive and well-studied. Our pre-clinical data suggest that it may be a candidate for repurposing as an inhaled therapy against COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-07-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.9533
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Is Inhaled Furosemide a Potential Therapeutic for COVID-19?

Brennecke, Anja / Villar, Laura / Wang, Zhiyu / Doyle, Lisa M / Meek, Autumn / Reed, Mark / Barden, Christopher / Weaver, Donald F

Am J Med Sci

Abstract	The potentially lethal infection caused by the novel Severe Acute Respiratory Disease Coronavirus-2 (SARS-CoV-2) has evolved into a global crisis. Following the initial viral infection is the host inflammatory response that frequently results in excessive secretion of inflammatory cytokines (e.g., IL-6 and TNFα), developing into a self-targeting, toxic "cytokine storm" causing critical pulmonary tissue damage. The need for a therapeutic that is available immediately is growing daily but the de novo development of a vaccine may take years. Therefore, repurposing of approved drugs offers a promising approach to address this urgent need. Inhaled furosemide, a small molecule capable of inhibiting IL-6 and TNFα, may be an agent capable of treating the Coronavirus Disease 2019 cytokine storm in both resource-rich and developing countries. Furosemide is a "repurpose-able" small molecule therapeutics, that is safe, easily synthesized, handled, and stored, and is available in reasonable quantities worldwide.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #457538
Database	COVID19

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Article ; Online: Small molecule therapeutics for COVID-19

Zhiyu Wang / Yanfei Wang / Prachi Vilekar / Seung-Pil Yang / Mayuri Gupta / Myong In Oh / Autumn Meek / Lisa Doyle / Laura Villar / Anja Brennecke / Imindu Liyanage / Mark Reed / Christopher Barden / Donald F. Weaver

PeerJ, Vol 8, p e

repurposing of inhaled furosemide

2020 Volume 9533

Abstract	The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia (“cytokine storm”). To address this immuno-inflammatory pathogenesis, multiple clinical trials have been proposed to evaluate anti-inflammatory biologic therapies targeting specific cytokines. However, despite the obvious clinical utility of such biologics, their specific applicability to COVID-19 has multiple drawbacks, including they target only one of the multiple cytokines involved in COVID-19’s immunopathy. Therefore, we set out to identify a small molecule with broad-spectrum anti-inflammatory mechanism of action targeting multiple cytokines of innate immunity. In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. This has enabled us to identify the loop diuretic furosemide as a candidate molecule. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Upon treatment with furosemide, LPS-induced production of pro-inflammatory cytokines was reduced, indicating that furosemide suppresses the M1 polarization, including IL-6 and TNF-α release. In addition, we found that furosemide promotes the production of anti-inflammatory cytokine products (IL-1RA, arginase), indicating M2 polarization. Accordingly, we conclude that furosemide is a reasonably potent inhibitor of IL-6 and TNF-α that is also safe, inexpensive and well-studied. Our pre-clinical data suggest that it may be a candidate for repurposing as an ...
Keywords	Furosemide ; COVID-19 ; Cytokine storm ; Hypercytokinemia ; Coronavirus ; Anti-inflammatory ; Medicine ; R ; Biology (General) ; QH301-705.5 ; covid19
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Small molecule therapeutics for COVID-19

PeerJ

repurposing of inhaled furosemide

2020 Volume 8, Page(s) e9533

Abstract	The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia (“cytokine storm”). To address this immuno-inflammatory pathogenesis, multiple clinical trials have been proposed to evaluate anti-inflammatory biologic therapies targeting specific cytokines. However, despite the obvious clinical utility of such biologics, their specific applicability to COVID-19 has multiple drawbacks, including they target only one of the multiple cytokines involved in COVID-19’s immunopathy. Therefore, we set out to identify a small molecule with broad-spectrum anti-inflammatory mechanism of action targeting multiple cytokines of innate immunity. In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. This has enabled us to identify the loop diuretic furosemide as a candidate molecule. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Upon treatment with furosemide, LPS-induced production of pro-inflammatory cytokines was reduced, indicating that furosemide suppresses the M1 polarization, including IL-6 and TNF-α release. In addition, we found that furosemide promotes the production of anti-inflammatory cytokine products (IL-1RA, arginase), indicating M2 polarization. Accordingly, we conclude that furosemide is a reasonably potent inhibitor of IL-6 and TNF-α that is also safe, inexpensive and well-studied. Our pre-clinical data suggest that it may be a candidate for repurposing as an inhaled therapy against COVID-19.
Keywords	General Biochemistry, Genetics and Molecular Biology ; General Neuroscience ; General Agricultural and Biological Sciences ; General Medicine ; covid19
Language	English
Publisher	PeerJ
Publishing country	us
Document type	Article ; Online
ZDB-ID	2703241-3
ISSN	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.9533
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide

PeerJ

Abstract: The novel coronavirus SARS-CoV-2 has become a global health concern The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response The latter may ... ...

Abstract	The novel coronavirus SARS-CoV-2 has become a global health concern The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia ("cytokine storm") To address this immuno-inflammatory pathogenesis, multiple clinical trials have been proposed to evaluate anti-inflammatory biologic therapies targeting specific cytokines However, despite the obvious clinical utility of such biologics, their specific applicability to COVID-19 has multiple drawbacks, including they target only one of the multiple cytokines involved in COVID-19's immunopathy Therefore, we set out to identify a small molecule with broad-spectrum anti-inflammatory mechanism of action targeting multiple cytokines of innate immunity In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition This has enabled us to identify the loop diuretic furosemide as a candidate molecule To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264 7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS) Upon treatment with furosemide, LPS-induced production of pro-inflammatory cytokines was reduced, indicating that furosemide suppresses the M1 polarization, including IL-6 and TNF-α release In addition, we found that furosemide promotes the production of anti-inflammatory cytokine products (IL-1RA, arginase), indicating M2 polarization Accordingly, we conclude that furosemide is a reasonably potent inhibitor of IL-6 and TNF-α that is also safe, inexpensive and well-studied Our pre-clinical data suggest that it may be a candidate for repurposing as an inhaled therapy against COVID-19
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #676849
Database	COVID19

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Article: Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe.

Gazzi, Thais / Brennecke, Benjamin / Atz, Kenneth / Korn, Claudia / Sykes, David / Forn-Cuni, Gabriel / Pfaff, Patrick / Sarott, Roman C / Westphal, Matthias V / Mostinski, Yelena / Mach, Leonard / Wasinska-Kalwa, Malgorzata / Weise, Marie / Hoare, Bradley L / Miljuš, Tamara / Mexi, Maira / Roth, Nicolas / Koers, Eline J / Guba, Wolfgang /

Alker, André / Rufer, Arne C / Kusznir, Eric A / Huber, Sylwia / Raposo, Catarina / Zirwes, Elisabeth A / Osterwald, Anja / Pavlovic, Anto / Moes, Svenja / Beck, Jennifer / Nettekoven, Matthias / Benito-Cuesta, Irene / Grande, Teresa / Drawnel, Faye / Widmer, Gabriella / Holzer, Daniela / van der Wel, Tom / Mandhair, Harpreet / Honer, Michael / Fingerle, Jürgen / Scheffel, Jörg / Broichhagen, Johannes / Gawrisch, Klaus / Romero, Julián / Hillard, Cecilia J / Varga, Zoltan V / van der Stelt, Mario / Pacher, Pal / Gertsch, Jürg / Ullmer, Christoph / McCormick, Peter J / Oddi, Sergio / Spaink, Herman P / Maccarrone, Mauro / Veprintsev, Dmitry B / Carreira, Erick M / Grether, Uwe / Nazaré, Marc

Chemical science

2022 Volume 13, Issue 19, Page(s) 5539–5545

Abstract: Despite its essential role in the (patho)physiology of several diseases, ... ...

Abstract	Despite its essential role in the (patho)physiology of several diseases, CB
Language	English
Publishing date	2022-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2559110-1
ISSN	2041-6539 ; 2041-6520
ISSN (online)	2041-6539
ISSN	2041-6520
DOI	10.1039/d1sc06659e
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