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- W3204608601 abstract "ABSTRACT Macrodomains are a class of conserved ADP-ribosylhydrolases expressed by viruses of pandemic concern, including coronaviruses and alphaviruses. Viral macrodomains are critical for replication and virus-induced pathogenesis; therefore, these enzymes are a promising target for antiviral therapy. However, no potent or selective viral macrodomain inhibitors currently exist, in part due to the lack of a high-throughput assay for this class of enzymes. Here, we developed a high-throughput ADP-ribosylhydrolase assay using the SARS-CoV-2 macrodomain Mac1. We performed a pilot screen which identified dasatinib and dihydralazine as ADP-ribosylhydrolase inhibitors. Importantly, dasatinib does not inhibit MacroD2, the closest Mac1 homolog in humans. Our study demonstrates the feasibility of identifying selective inhibitors based on ADP-ribosylhydrolase activity, paving the way for screening large compound libraries to identify improved macrodomain inhibitors and explore their potential as antiviral therapies for SARS-CoV-2 and future viral threats." @default.
- W3204608601 created "2021-10-11" @default.
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- W3204608601 date "2021-10-07" @default.
- W3204608601 modified "2023-09-27" @default.
- W3204608601 title "High-throughput Activity Assay for Screening Inhibitors of the SARS-CoV-2 Mac1 Macrodomain" @default.
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- W3204608601 doi "https://doi.org/10.1101/2021.10.07.463234" @default.
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