Nat Commun . Structural Plasticity of SARS-CoV-2 3CL M pro Active Site Cavity Revealed by Room Temperature X-ray Crystallography

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Nat Commun


. 2020 Jun 24;11(1):3202.
doi: 10.1038/s41467-020-16954-7.
Structural Plasticity of SARS-CoV-2 3CL M ^pro Active Site Cavity Revealed by Room Temperature X-ray Crystallography


Daniel W Kneller ¹ , Gwyndalyn Phillips ¹ , Hugh M O'Neill ¹ , Robert Jedrzejczak ^{2 3} , Lucy Stols ² , Paul Langan ¹ , Andrzej Joachimiak ^{2 3 4} , Leighton Coates ⁵ , Andrey Kovalevsky ⁶



Affiliations

• PMID: 32581217
• DOI: 10.1038/s41467-020-16954-7

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^pro 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^pro, 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.