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Aprotinin Inhibits SARS-CoV-2 Replication

Bojkova, Denisa, Bechtel, Marco, McLaughlin, Katie-May, McGreig, Jake E., Klann, Kevin, Bellinghausen, Carla, Rohde, Gernot, Jonigk, Danny, Braubach, Peter, Ciesek, Sandra, and others. (2020) Aprotinin Inhibits SARS-CoV-2 Replication. Cells, 9 (11). Article Number 2377. E-ISSN 2073-4409. (doi:10.3390/cells9112377) (KAR id:83961)

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https://dx.doi.org/10.3390/cells9112377

Abstract

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is the cause of the current coronavirus disease 19 (COVID-19) pandemic. Protease inhibitors are under consideration as virus entry inhibitors that prevent the cleavage of the coronavirus spike (S) protein by cellular proteases. Herein, we showed that the protease inhibitor aprotinin (but not the protease inhibitor SERPINA1/alpha-1 antitrypsin) inhibited SARS-CoV-2 replication in therapeutically achievable concentrations. An analysis of proteomics and translatome data indicated that SARS-CoV-2 replication

is associated with a downregulation of host cell protease inhibitors. Hence, aprotinin may compensate for downregulated host cell proteases during later virus replication cycles. Aprotinin displayed anti-SARS-CoV-2 activity in different cell types (Caco2, Calu-3, and primary bronchial epithelial cell air–liquid interface cultures) and against four virus isolates. In conclusion, therapeutic aprotinin concentrations exert anti-SARS-CoV-2 activity. An approved aprotinin aerosol may have potential for the early local control of SARS-CoV-2 replication and the prevention of COVID-19 progression to a severe, systemic disease.

Item Type: Article
DOI/Identification number: 10.3390/cells9112377
Uncontrolled keywords: severe acute respiratory syndrome coronavirus; severe acute respiratory syndrome coronavirus 2; 2019-nCoV; COVID-19; antiviral; drug discovery; aprotinin
Subjects: Q Science > QR Microbiology > QR355 Virology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 06 Nov 2020 12:39 UTC
Last Modified: 09 Nov 2020 09:19 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/83961 (The current URI for this page, for reference purposes)
Wass, Mark N.: https://orcid.org/0000-0001-5428-6479
Michaelis, Martin: https://orcid.org/0000-0002-5710-5888
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