PT  - JOURNAL ARTICLE
AU  - Steven S. Good
AU  - Jonna Westover
AU  - Kie Hoon Jung
AU  - Paolo La Colla
AU  - Gabriella Collu
AU  - Adel Moussa
AU  - Bruno Canard
AU  - Jean-Pierre Sommadossi
TI  - AT-527 is a potent <em>in vitro</em> replication inhibitor of SARS-CoV-2, the virus responsible for the COVID-19 pandemic
AID  - 10.1101/2020.08.11.242834
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.11.242834
4099  - http://biorxiv.org/content/early/2020/08/11/2020.08.11.242834.1.short
4100  - http://biorxiv.org/content/early/2020/08/11/2020.08.11.242834.1.full
AB  - AT-527, an orally administered double prodrug of a guanosine nucleotide analog, has been shown previously to be highly efficacious and well tolerated in HCV-infected subjects. Herein we report the potent in vitro activity of AT-511, the free base form of AT-527, against several coronaviruses, including SARS-CoV-2, the causative agent of COVID-19. In normal human airway epithelial (HAE) cell preparations, the average concentration of AT-511 required to inhibit replication of SARS-CoV-2 by 90% (EC90) was 0.5 µM, very similar to the EC90 for AT-511 against HCoV-229E, HCoV-OC43 and SARS-CoV in Huh-7 cells. No cytotoxicity was observed for AT-511 in any of the antiviral assays up to the highest concentration tested (100 µM). Surprisingly, AT-511 was 30-fold less active against MERS-CoV. This differential activity may provide a clue to the apparent unique mechanism of action of the guanosine triphosphate analog formed from AT-527.Competing Interest StatementThe authors affiliated with Atea Pharmaceuticals, Inc. are employees of the company and own company stock. The other authors have no conflict of interest to report.