| Autor: |
Yount, Boyd L., Baric, Ralph S., Ma, Bin, Agostini, Maria L., Graham, Rachel L., Feng, Joy Y., Stevens, Laura J., Du Pont, Venice, Dinnon III, Kenneth H., Lu, Xiaotao, Gralinski, Lisa E., George, Amelia S., Hughes, Tia M., Gully, Kendra, Pitts, Jared, Brown, Ariane J., Cihlar, Tomas, Martinez, David R., Bilello, John P., Sheahan, Timothy P., Murakami, Eisuke, Pruijssers, Andrea J., Schaefer, Alexandra, Leist, Sarah R., Babusis, Darius, Porter, Danielle P., Chappell, James D., Perry, Jason K. |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| DOI: |
10.17615/r4vm-4j84 |
| Popis: |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 μM). Weaker activity is observed in Vero E6 cells (EC50 = 1.65 μM) because of 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 the chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared with vehicle-treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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