Denisa Bojkova, Marco Bechtel, Katie-May McLaughlin, Jake E. McGreig, Kevin Klann, Carla Bellinghausen, Gernot Gerhard Ulrich Rohde, Danny David Jonigk, Peter Braubach, Sandra Ciesek, Christian Münch, Mark N. Wass, Martin Michaelis, Jindrich Cinatl
- 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.
MetadatenAuthor: | Denisa BojkovaORCiDGND, Marco Bechtel, Katie-May McLaughlin, Jake E. McGreigORCiD, Kevin KlannORCiDGND, Carla BellinghausenORCiD, Gernot Gerhard Ulrich RohdeORCiDGND, Danny David JonigkORCiDGND, Peter Braubach, Sandra CiesekORCiDGND, Christian MünchORCiD, Mark N. WassORCiD, Martin MichaelisORCiDGND, Jindrich CinatlORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-564665 |
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DOI: | https://doi.org/10.3390/cells9112377 |
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ISSN: | 2073-4409 |
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Parent Title (English): | Cells |
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Publisher: | MDPI |
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Place of publication: | Basel |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2020/10/30 |
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Date of first Publication: | 2020/10/30 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2020/11/12 |
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Tag: | 2019-nCoV; COVID-19; antiviral; aprotinin; drug discovery; severe acute respiratory syndrome coronavirus; severe acute respiratory syndrome coronavirus 2 |
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Volume: | 9 |
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Issue: | 2377 |
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Page Number: | 13 |
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HeBIS-PPN: | 475949064 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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