Camostat mesylate against SARS-CoV-2 and COVID-19-Rationale, dosing and safety.

Tytuł:: Camostat mesylate against SARS-CoV-2 and COVID-19-Rationale, dosing and safety.
Autorzy:: Breining P; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Frølund AL; Medical School, Faculty of health, Aarhus University, Aarhus, Denmark.
Højen JF; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Gunst JD; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Staerke NB; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Saedder E; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
Cases-Thomas M; Senechaem Ltd., Reading, UK.
Little P; Lundbeck Foundation, Copenhagen, Denmark.
Nielsen LP; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
Søgaard OS; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Kjolby M; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.; University of Dundee, Dundee, Scotland.
Źródło:: Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2021 Feb; Vol. 128 (2), pp. 204-212. Date of Electronic Publication: 2020 Nov 22.
Typ publikacji:: Journal Article; Review
Język:: English
Imprint Name(s):: Publication: <2005-> : Oxford : Blackwell
Original Publication: Copenhagen, Denmark : Oxford, UK : Nordic Pharmacological Society Distributed by Blackwell Munksgaard, 2004-
MeSH Terms:: COVID-19 Drug Treatment*
Antiviral Agents/*therapeutic use
Esters/*therapeutic use
Guanidines/*therapeutic use
Serine Proteinase Inhibitors/*therapeutic use
Animals ; Antiviral Agents/administration & dosage ; Antiviral Agents/adverse effects ; Drug Repositioning ; Esters/administration & dosage ; Esters/adverse effects ; Guanidines/administration & dosage ; Guanidines/adverse effects ; Humans ; Mice ; Patient Safety ; Serine Endopeptidases/drug effects ; Serine Proteinase Inhibitors/administration & dosage ; Serine Proteinase Inhibitors/adverse effects
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Grant Information:: Lundbeckfonden
Contributed Indexing:: Keywords: Antiviral drugs < Viral infections; Camostat mesylate; Infection < Immunotoxicology; Lung; drug repurposing; pulmonary or respiratory system < Respiratory toxicology; tmprss2
Substance Nomenclature:: 0 (Antiviral Agents)
0 (Esters)
0 (Guanidines)
0 (Serine Proteinase Inhibitors)
0FD207WKDU (camostat)
EC 3.4.21.- (Serine Endopeptidases)
EC 3.4.21.- (TMPRSS2 protein, human)
Entry Date(s):: Date Created: 20201111 Date Completed: 20210121 Latest Revision: 20221207
Update Code:: 20240105
DOI:: 10.1111/bcpt.13533
PMID:: 33176395
: Czasopismo naukowe

Pełny tekst

The coronavirus responsible for COVID-19, SARS-CoV-2, utilizes a viral membrane spike protein for host cell entry. For the virus to engage in host membrane fusion, SARS-CoV-2 utilizes the human transmembrane surface protease, TMPRSS2, to cleave and activate the spike protein. Camostat mesylate, an orally available well-known serine protease inhibitor, is a potent inhibitor of TMPRSS2 and has been hypothesized as a potential antiviral drug against COVID-19. In vitro human cell and animal studies have shown that camostat mesylate inhibits virus-cell membrane fusion and hence viral replication. In mice, camostat mesylate treatment during acute infection with influenza, also dependent on TMPRSS2, leads to a reduced viral load. The decreased viral load may be associated with an improved patient outcome. Because camostat mesylate is administered as an oral drug, it may be used in outpatients as well as inpatients at all disease stages of SARS-CoV-2 infection if it is shown to be an effective antiviral agent. Clinical trials are currently ongoing to test whether this well-known drug could be repurposed and utilized to combat the current pandemic. In the following, we will review current knowledge on camostat mesylate mode of action, potential benefits as an antiviral agent and ongoing clinical trials.
(© 2020 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

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