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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; Münch, Christian; Wass, Mark N; Michaelis, Martin; Cinatl, Jindrich.
  • Bojkova D; Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany.
  • Bechtel M; Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany.
  • McLaughlin KM; School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
  • McGreig JE; School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
  • Klann K; Faculty of Medicine, Institute of Biochemistry II, Goethe University, 60590 Frankfurt am Main, Germany.
  • Bellinghausen C; Department of Respiratory Medicine and Allergology, University Hospital, Goethe University, 60590 Frankfurt am Main, Germany.
  • Rohde G; Department of Respiratory Medicine and Allergology, University Hospital, Goethe University, 60590 Frankfurt am Main, Germany.
  • Jonigk D; Institute of Pathology, Hannover Medical School (MHH), 30625 Hannover, Germany.
  • Braubach P; 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.
  • Ciesek S; Institute of Pathology, Hannover Medical School (MHH), 30625 Hannover, Germany.
  • Münch C; 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.
  • Wass MN; Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany.
  • Michaelis M; German Center for Infection Research, DZIF, External Partner Site, 60596 Frankfurt am Main, Germany.
  • Cinatl J; Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch Translational Medicine und Pharmacology, 60596 Frankfurt am Main, Germany.
Cells ; 9(11)2020 10 30.
Article in English | MEDLINE | ID: covidwho-921181
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Replication / Aprotinin / SARS-CoV-2 / COVID-19 Drug Treatment Limits: Animals / Humans Language: English Year: 2020 Document Type: Article Affiliation country: Cells9112377

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Replication / Aprotinin / SARS-CoV-2 / COVID-19 Drug Treatment Limits: Animals / Humans Language: English Year: 2020 Document Type: Article Affiliation country: Cells9112377