The Story So Far - StructuralGenomicsConsortium/CNP25-CHIKV-nsP3-Macrodomain GitHub Wiki

The starting point for the project is the dataset derived from a fragment screen vs the macrodomain carried out at the Diamond Light Source by Daren Fearon and Jasmin Aschenbrenner in late 2023. The data are being refined (January 2024).

The aim of the project is to use these fragments to design a chemical probe binding to the CHIKV nsp3 macrodomain, particularly to ADP-Ribose site in where the substrate binds and where the active site residue(s) are located. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic 1, 2, 3. By finding molecules with high affinity for this site, the substrate wouldn't be able to bind and no reaction would occur.

Here are a few fragments have been identified so far by DLS team in nucleotide binding site of CHIKV nsp3 macrodomain:

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You can also see other few fragments which have also been identified by DLS team in different sites of CHIKV nsp3 macrodomainTarget meeting's slides-7 Dec 2023

A kick-off meeting was held Feb 5th 2024 to discuss the compounds screening and triage.