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 [1]. 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 [2]. In October 2020 anti-SARS-CoV-2 activity was reported in preprint format [3], which converted to full peer reviewed publication in March 2021 [4].
AT-527 was developed by Atea Pharmaceuticals [5]. 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. |
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References |
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, 63 (12). [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. |