TY  - INPR
A1  - Bojkova, Denisa
A1  - McGreig, Jake E.
A1  - McLaughlin, Katie-May
A1  - Masterson, Stuart G.
A1  - Widera, Marek
A1  - Krähling, Verena
A1  - Ciesek, Sandra
A1  - Wass, Mark N.
A1  - Michaelis, Martin
A1  - Cinatl, Jindrich
T1  - SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles
T2  - bioRxiv
N2  - 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.
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72725
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-727259
IS  - 2020.04.03.024257
ER  -