Structural plasticity of SARS-CoV-2 3CL M<sup>pro</sup> active site cavity revealed by room temperature X-ray crystallography.

Kneller, Daniel W; Phillips, Gwyndalyn; O'Neill, Hugh M; Jedrzejczak, Robert; Stols, Lucy; Langan, Paul; Joachimiak, Andrzej; Coates, Leighton et al. · Nat Commun · 2020

basic_science · Level V

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Abstract

The COVID-19 disease caused by the SARS-CoV-2 coronavirus has become a pandemic health crisis. An attractive target for antiviral inhibitors is the main protease 3CL M<sup>pro</sup> due to its essential role in processing the polyproteins translated from viral RNA. Here we report the room temperature X-ray structure of unliganded SARS-CoV-2 3CL M<sup>pro</sup>, revealing the ligand-free structure of the active site and the conformation of the catalytic site cavity at near-physiological temperature. Comparison with previously reported low-temperature ligand-free and inhibitor-bound structures suggest that the room temperature structure may provide more relevant information at physiological temperatures for aiding in molecular docking studies.

Medical subject headings