TY  - JOUR
A1  - Bojkova, Denisa
A1  - Bechtel, Marco
A1  - McLaughlin, Katie-May
A1  - McGreig, Jake E.
A1  - Klann, Kevin
A1  - Bellinghausen, Carla
A1  - Rohde, Gernot Gerhard Ulrich
A1  - Jonigk, Danny David
A1  - Braubach, Peter
A1  - Ciesek, Sandra
A1  - Münch, Christian
A1  - Wass, Mark N.
A1  - Michaelis, Martin
A1  - Cinatl, Jindrich
T1  - Aprotinin inhibits SARS-CoV-2 replication
T2  - Cells
N2  - 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.
KW  - severe acute respiratory syndrome coronavirus
KW  - severe acute respiratory syndrome coronavirus 2
KW  - 2019-nCoV
KW  - COVID-19
KW  - antiviral
KW  - drug discovery
KW  - aprotinin
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56466
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-564665
SN  - 2073-4409
VL  - 9
IS  - 2377
PB  - MDPI
CY  - Basel
ER  -