AT-527 is a potent in vitro replication inhibitor of SARS-CoV-2, the virus responsible for the COVID-19 pandemic

• Published in: bioRxiv 2020-08
• Main Authors: Good, Steven S, Westover, Jonna, Kie-Hoon Jung, Paolo La Colla, Collu, Gabriella, Moussa, Adel, Canard, Bruno, Sommadossi, Jean-Pierre
• Format: Article
• Language: English
• Subjects: Coronaviruses; COVID-19; Cytotoxicity; Guanosine; Nucleotide analogs; Oral administration; Pandemics; Replication; Severe acute respiratory syndrome coronavirus 2
• DOI: 10.1101/2020.08.11.242834

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 Statement The 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.