During the process of finalising our data, we were contacted by the James Fraser laboratory and QBI Coronovirus Research Group collaborators at the University of California, San Francisco who had made a similar, independent effort also running a fragment screen on the SARS-CoV-2 macrodomain, however, with a slightly different crystal form of the macrodomain and fragment libraries.
The Fraser team identified additional 13 hits, 3 of which were in the active site. Together with the XChem data, the two fragment screens give unique insights for developing novel chemical matter targeting the active site of the macrodomain, and show the way to developing effective, first-in-class inhibitors of the SARS-CoV-2 Nsp3 macrodomain .
The Ahel lab will now join forces with the von Delft and Fraser groups, as well as recruiting further collaborators, in an international collaboration sharing expertise and resources in computational and medicinal chemistry as well as crystallographic, biochemical and up to in vivo inhibitor characterisation, in the hope to contribute a step forward to combat the COVID-19 pandemic.
Both our and the Fraser lab data can be viewed on Fragalysis.
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