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Cited by 510

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice

Open access
Pruijssers, Andrea J., George, Amelia S., Schäfer, Alexandra, Leist, Sarah R., Gralinksi, Lisa E., Dinnon, Kenneth H., Yount, Boyd L., Agostini, Maria L., Stevens, Laura J., Chappell, James D., Lu, Xiaotao, Hughes, Tia M., Gully, Kendra, Martinez, David R., Brown, Ariane J., Graham, Rachel L., Perry, Jason K., Du Pont, Venice, Pitts, Jared, Ma, Bin, Babusis, Darius, Murakami, Eisuke, Feng, Joy Y., Bilello, John P., Porter, Danielle P., Cihlar, Tomas, Baric, Ralph S., Denison, Mark R., Sheahan, Timothy P.·2020·Cell Reports

Abstract

SUMMARY 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 (EC 50 = 0.01 μM). Weaker activity was observed in Vero E6 cells (EC 50 = 1.65 μM) 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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Crossref · 10.1016/j.celrep.2020.107940

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Metadata

Authors
Pruijssers, A. J., George, A. S., Schäfer, A., Leist, S. R., Gralinksi, L. E., Dinnon, K. H., Yount, B. L., Agostini, M. L., Stevens, L. J., Chappell, J. D., Lu, X., Hughes, T. M., Gully, K., 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.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2020-07
Volume
32
Issue
3
Pages
107940
ISSN
2211-1247 (ISSN-L)
OpenAlex
W3041968020
Cited by
510
References
12
FWCI
12.43
Type
journal article
Language
en
Open access
gold

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