Diamond Protease and Fragment Data - OpenSourceSarsCoV2/LivingResourceReview GitHub Wiki

Short description

The Diamond Light Source is a synchrotron facility located in the UK that is utilised for a range of scientific areas including the investigation of protein structures and properties. During the coronavirus pandemic, Diamond have used their facility to generate data on protein targets and fragments, all of which have been made publicly available. Notably, by solving a high-resolution structure (1.39 Å) of the SARS-CoV-2 main protease, Diamond have been able to use this to perform a screen of multiple fragment libraries to identify the most promising hits for fragment-based drug discovery. This screen resulted in 74 high interest hits and the full results of this screen have been made available to researchers and initiatives such as the PostEra COVID Moonshot project. This main protease structure has also been used to screen for covalent probes from a library of electrophile fragments.

Links and references

Main Protease Structure and XChem Fragment Screen: https://www.diamond.ac.uk/covid-19/for-scientists/Main-protease-structure-and-XChem.html

SARS-CoV-2 Main Protease with Unliganded Active Site: https://www.wwpdb.org/pdb?id=pdb_00006y84

Resnick E, Bradley A, Gan J, et al.: Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening. J. Am. Chem. Soc. 2019; 141(22): 8951-8968. http://doi.org/10.1021/jacs.9b02822