Researchers from the University of Kent, the Goethe-University in Frankfurt am Main (Germany), and the Hannover Medical School (Germany) have identified a drug with the potential to provide a treatment for COVID-19.
The international team led by Professor Martin Michaelis, Dr. Mark Wass (both School of Biosciences, University of Kent), and Professor Jindrich Cinatl (Institute of Medical Virology, Goethe-University) found that the approved protease inhibitor aprotinin displayed activity against SARS-CoV-2, in concentrations that are achieved in patients.
Protease inhibitors are under consideration as virus entry inhibitors that prevent the cleavage of the coronavirus spike (S) protein by cellular
proteases. In this paper it’s shown 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.
Aprotinin aerosols are approved in Russia for the treatment of influenza and could be readily tested for the treatment of COVID-19.
Professor Martin Michaelis said: ‘The aprotinin aerosol has been reported to be tolerated extremely well in influenza patients. Hence, it may have a particular potential to prevent severe COVID-19 disease when applied early after diagnosis.’
Human fresh frozen plasma is a source of powerful protease inhibitors and thus can have the same action of aprotinin against SARS-CoV-2.