Next Article in Journal
Rab11A Functions as a Negative Regulator of Osteoclastogenesis through Dictating Lysosome-Induced Proteolysis of c-fms and RANK Surface Receptors
Previous Article in Journal
Human Autopsy-Derived Scalp Fibroblast Biobanking for Age-Related Neurodegenerative Disease Research
Article

Aprotinin Inhibits SARS-CoV-2 Replication

1
Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany
2
School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK
3
Faculty of Medicine, Institute of Biochemistry II, Goethe University, 60590 Frankfurt am Main, Germany
4
Department of Respiratory Medicine and Allergology, University Hospital, Goethe University, 60590 Frankfurt am Main, Germany
5
Institute of Pathology, Hannover Medical School (MHH), 30625 Hannover, Germany
6
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), The German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Hannover Medical School (MHH), 30625 Hannover, Germany
7
German Center for Infection Research, DZIF, External Partner Site, 60596 Frankfurt am Main, Germany
8
Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch Translational Medicine und Pharmacology, 60596 Frankfurt am Main, Germany
9
Frankfurt Cancer Institute, Goethe University, 60596 Frankfurt am Main, Germany
10
Cardio-Pulmonary Institute, Goethe University, 60590 Frankfurt am Main, Germany
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(11), 2377; https://doi.org/10.3390/cells9112377
Received: 28 June 2020 / Revised: 15 October 2020 / Accepted: 28 October 2020 / Published: 30 October 2020
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. View Full-Text
Keywords: severe acute respiratory syndrome coronavirus; severe acute respiratory syndrome coronavirus 2; 2019-nCoV; COVID-19; antiviral; drug discovery; aprotinin severe acute respiratory syndrome coronavirus; severe acute respiratory syndrome coronavirus 2; 2019-nCoV; COVID-19; antiviral; drug discovery; aprotinin
Show Figures

Figure 1

MDPI and ACS Style

Bojkova, D.; Bechtel, M.; McLaughlin, K.-M.; McGreig, J.E.; Klann, K.; Bellinghausen, C.; Rohde, G.; Jonigk, D.; Braubach, P.; Ciesek, S.; Münch, C.; Wass, M.N.; Michaelis, M.; Cinatl, J., Jr. Aprotinin Inhibits SARS-CoV-2 Replication. Cells 2020, 9, 2377. https://doi.org/10.3390/cells9112377

AMA Style

Bojkova D, Bechtel M, McLaughlin K-M, McGreig JE, Klann K, Bellinghausen C, Rohde G, Jonigk D, Braubach P, Ciesek S, Münch C, Wass MN, Michaelis M, Cinatl J Jr.. Aprotinin Inhibits SARS-CoV-2 Replication. Cells. 2020; 9(11):2377. https://doi.org/10.3390/cells9112377

Chicago/Turabian Style

Bojkova, Denisa, Marco Bechtel, Katie-May McLaughlin, Jake E. McGreig, Kevin Klann, Carla Bellinghausen, Gernot Rohde, Danny Jonigk, Peter Braubach, Sandra Ciesek, Christian Münch, Mark N. Wass, Martin Michaelis, and Jindrich Cinatl Jr. 2020. "Aprotinin Inhibits SARS-CoV-2 Replication" Cells 9, no. 11: 2377. https://doi.org/10.3390/cells9112377

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop