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

Bojkova, D.; McGreig, J. E.; McLaughlin, K.-M.; Masterson, S. G.; Widera, M.; Kraehling, V.; Ciesek, S.; Wass, M. N.; Michaelis, M.; Cinatl, J. N.

doi:10.1101/2020.04.03.024257

bioRxiv · 10.1101/2020.04.03.024257

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

Bojkova, D.·McGreig, J. E.·McLaughlin, K.-M.·Masterson, S. G.·Widera, M.·Kraehling, V.·Ciesek, S.·Wass, M. N.·Michaelis, M.·Cinatl, J. N.

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Abstract

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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Bojkova, D., McGreig, J. E., McLaughlin, K.-M., Masterson, S. G., Widera, M., Kraehling, V., Ciesek, S., Wass, M. N., Michaelis, M., Cinatl, J. N.. 2020-04-05. SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles. https://doi.org/10.1101/2020.04.03.024257

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