Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice.

Pruijssers, A. J.; George, A. S.; Schäfer, A.; Leist, S. R.; Gralinski, L. E.; Dinnon, K. H.; Yount, B. L.; Agostini, M. L.; Stevens, L. J.; Chappell, J. D.; Lu, X.; Hughes, T. M.; Gully, K. L.; Martinez, D. R.; Brown, A. J.; Graham, R. L.; Perry, J. K.; Du Pont, V.; Pitts, J.; Ma, B.; Babusis, D.; Murakami, E.; Feng, J. Y.; Bilello, J. P.; Porter, D. P.; Cihlar, T.; Baric, R. S.; Denison, M. R.; Sheahan, T. P.

doi:10.1101/2020.04.27.064279

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bioRxiv · 10.1101/2020.04.27.064279

Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice.

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 M). Weaker activity was observed in Vero E6 cells (EC50 = 1.65 M) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminished lung viral load and improved pulmonary function as compared to vehicle treated animals. These data provide evidence that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.

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Pruijssers, A. J., George, A. S., Schäfer, A., Leist, S. R., Gralinski, L. E., Dinnon, K. H., Yount, B. L., Agostini, M. L., Stevens, L. J., Chappell, J. D., Lu, X., Hughes, T. M., Gully, K. L., Martinez, D. R., Brown, A. J., Graham, R. L., Perry, J. K., Du Pont, V., Pitts, J., Ma, B., Babusis, D., Murakami, E., Feng, J. Y., Bilello, J. P., Porter, D. P., Cihlar, T., Baric, R. S., Denison, M. R., Sheahan, T. P.. 2020-04-27. Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice.. https://doi.org/10.1101/2020.04.27.064279

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