tetano
Editor, Senior Moderator
Cells
. 2020 Oct 30;9(11):E2377.
doi: 10.3390/cells9112377.
Aprotinin Inhibits SARS-CoV-2 Replication
Denisa Bojkova[SUP] 1 [/SUP], Marco Bechtel[SUP] 1 [/SUP], Katie-May McLaughlin[SUP] 2 [/SUP], Jake E McGreig[SUP] 2 [/SUP], Kevin Klann[SUP] 3 [/SUP], Carla Bellinghausen[SUP] 4 [/SUP], Gernot Rohde[SUP] 4 [/SUP], Danny Jonigk[SUP] 5 6 [/SUP], Peter Braubach[SUP] 5 6 [/SUP], Sandra Ciesek[SUP] 1 7 8 [/SUP], Christian M?nch[SUP] 3 9 10 [/SUP], Mark N Wass[SUP] 2 [/SUP], Martin Michaelis[SUP] 2 [/SUP], Jindrich Cinatl Jr[SUP] 1 [/SUP]
Affiliations
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.
Keywords: 2019-nCoV; COVID-19; antiviral; aprotinin; drug discovery; severe acute respiratory syndrome coronavirus; severe acute respiratory syndrome coronavirus 2.
. 2020 Oct 30;9(11):E2377.
doi: 10.3390/cells9112377.
Aprotinin Inhibits SARS-CoV-2 Replication
Denisa Bojkova[SUP] 1 [/SUP], Marco Bechtel[SUP] 1 [/SUP], Katie-May McLaughlin[SUP] 2 [/SUP], Jake E McGreig[SUP] 2 [/SUP], Kevin Klann[SUP] 3 [/SUP], Carla Bellinghausen[SUP] 4 [/SUP], Gernot Rohde[SUP] 4 [/SUP], Danny Jonigk[SUP] 5 6 [/SUP], Peter Braubach[SUP] 5 6 [/SUP], Sandra Ciesek[SUP] 1 7 8 [/SUP], Christian M?nch[SUP] 3 9 10 [/SUP], Mark N Wass[SUP] 2 [/SUP], Martin Michaelis[SUP] 2 [/SUP], Jindrich Cinatl Jr[SUP] 1 [/SUP]
Affiliations
- PMID: 33143316
- DOI: 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.
Keywords: 2019-nCoV; COVID-19; antiviral; aprotinin; drug discovery; severe acute respiratory syndrome coronavirus; severe acute respiratory syndrome coronavirus 2.