Author:
Good Steven S.,Westover Jonna,Jung Kie-Hoon,La Colla Paolo,Collu Gabriella,Moussa Adel,Canard Bruno,Sommadossi Jean-Pierre
Abstract
ABSTRACTAT-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.
Publisher
Cold Spring Harbor Laboratory
Reference13 articles.
1. Remdesivir for the treatment of COVID-19 – Preliminary report;N. Engl. J. Med. Jul,2020
2. Safety, pharmacokinetics, and antiviral activity of AT-527, a novel purine nucleotide prodrug, in hepatitis C virus-infected subjects with or without cirrhosis;Antimicrob. Agents Chemother,2019
3. Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19;ACS Cent. Sci,2020
4. Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA
5. Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus;PLoS ONE,2020
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