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Synonyms: AT-527 | AT527 | RO-7496998 | RO7496998
Compound class: Synthetic organic
Comment: AT-527 is the orally bioavailable hemi-sulfate salt of AT-511, which is a direct-acting antiviral compound that disrupts activity of the viral RNA polymerase . It was originally developed to combat hepatitis C (HCV) infection, but has been redeployed for SARS-CoV-2. Chemically AT-527 is a phosphoramidate purine nucleotide and it is metabolised to a biologically active guanosine triphosphate analogue in vivo. Preclinical results showing pan-genotype activity against HCV were published in early 2020 . In October 2020 anti-SARS-CoV-2 activity was reported in preprint format , which converted to full peer reviewed publication in March 2021 .
AT-527 was developed by Atea Pharmaceuticals . In October 2020 it was announced that Roche were purchasing the rights to AT-527 (and gave it the research code RO7496998) outside of the US. In the same press release, it was revealed that AT-527 would be evaluated in Phase 3 trial in early 2021 to determine its efficacy as an early treatment for COVID-19 in non-hospitalised patients.
This is a complex molecule with 5 stereo-centres, so there are several CIDs with the same connectivity in PubChem. We chose to represent the molecule from CID 122527275 as it is linked to a FDA UNique Ingredient Identifier (UNII) code. This CID represents the parent molecule. For the hemi-sulfate salt structure see PubChem CID 155926085.
1. Berliba E, Bogus M, Vanhoutte F, Berghmans PJ, Good SS, Moussa A, Pietropaolo K, Murphy RL, Zhou XJ, Sommadossi JP. (2019)
Safety, pharmacokinetics and antiviral activity of AT-527, a novel purine nucleotide prodrug, in HCV-infected subjects with and without cirrhosis.
Antimicrob Agents Chemother, [Epub ahead of print]. [PMID:31570394]
2. Good SS, Moussa A, Zhou XJ, Pietropaolo K, Sommadossi JP. (2020)
Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus.
PLoS One, 15 (1): e0227104. [PMID:31914458]
3. Good SS, Westover J, Jung KH, La Colla P, Collu G, Moussa A, Canard B, Sommadossi J-P. (2020)
AT-527 is a potent in vitro replication inhibitor of SARS-CoV-2, the virus responsible for the COVID-19 pandemic.
bioRxiv, Preprint. DOI: 10.1101/2020.08.11.242834
4. Good SS, Westover J, Jung KH, Zhou XJ, Moussa A, La Colla P, Collu G, Canard B, Sommadossi JP. (2021)
AT-527, a Double Prodrug of a Guanosine Nucleotide Analog, Is a Potent Inhibitor of SARS-CoV-2 In Vitro and a Promising Oral Antiviral for Treatment of COVID-19.
Antimicrob Agents Chemother, 65 (4). DOI: 10.1128/AAC.02479-20 [PMID:33558299]
5. Moussa A, Sommadossi J-P. (2018)
Nucleotide hemi-sulfate salt for the treatment of hepatitis c virus.
Patent number: WO2018144640A1. Assignee: Atea Pharmaceuticals, Inc.. Priority date: 01/02/2017. Publication date: 09/08/2018.