SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles

  • SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV. Moreover, cellular ACE2 (SARS-CoV-2 receptor) and TMPRSS2 (enables virus entry via S protein cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.

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Author:Denisa BojkovaORCiDGND, Jake E. McGreigORCiD, Katie-May McLaughlin, Stuart G. Masterson, Marek WideraORCiDGND, Verena KrählingORCiDGND, Sandra CiesekORCiDGND, Mark N. WassORCiD, Martin MichaelisORCiDGND, Jindrich CinatlORCiDGND
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2020/04/05
Date of first Publication:2020/04/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/03/22
Page Number:28
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International