COVID-19 drug- Aprotinin may prevent replication of coronavirus
Researchers at Goethe University, University of Kent and the Hannover Medical School have found that the protease inhibitor aprotinin can inhibit virus replication by preventing SARS-CoV2 entry into host cells. In addition aprotinin appears to compensate for a SARS-CoV2-induced reduction of endogenous protease inhibitors in virus-infected cells.
Severeacute 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.
Influenza viruses require host cell proteases for cell entry in a similar way as coronaviruses. Hence, an aprotinin aerosol is already approved in Russia for the treatment of influenza.
In cell culture experiments with various cell types, the international scientific team led by Professor Jindrich Cinatl, Institute for Medical Virology at the University Hospital Frankfurt, Professor Martin Michaelis, and Dr Mark Wass (both University of Kent) demonstrated that the protease inhibitor aprotinin can inhibit virus replication by preventing SARS-CoV2 entry into host cells.
Professor Jindrich Cinatl said: "Our findings show that aprotinin is effective against SARS-CoV2 in concentrations that can be achieved in patients. In aprotinin we have a drug candidate for the treatment of COVID-19 that is already approved for other indications and could readily be tested in patients.
Therapeutic aprotinin concentrations inhibit SARS-CoV-2 replication as entry inhibitors and by compensating for downregulated cellular protease inhibitors during later replication cycles. Local treatment of the respiratory tract using an aprotinin aerosol, which is approved in Russia for the treatment of influenza , may be a particularly promising strategy to suppress virus replication and lung injury early and to prevent COVID-19 progression into a severe, systemic disease.
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Denisa Bojkova, 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, Jindrich Cinatl jr. Aprotinin inhibits SARS-CoV-2 replication. Cells 2020, https://www.mdpi.com/2073-4409/9/11/2377