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Instruments / Technical Area	Publication Details	Published	Actions
Krios II-Titan Krios II at Diamond	An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition Gabriela Dias Noske , Yun Song , Rafaela Sachetto Fernandes , Rod Chalk , Haitem Elmassoudi , Lizbe Koekemoer , C. David Owen , Tarick J. El-Baba , Carol V. Robinson , Glaucius Oliva , Andre Schutzer Godoy Nature Communications 14 DOI: 10.1038/s41467-023-37035-5 Diamond Proposal Number(s): [27083, 29349] Open Access Show Abstract ▼ Abstract: The main protease from SARS-CoV-2 (Mpro) is responsible for cleavage of the viral polyprotein. Mpro self-processing is called maturation, and it is crucial for enzyme dimerization and activity. Here we use C145S Mpro to study the structure and dynamics of N-terminal cleavage in solution. Native mass spectroscopy analysis shows that mixed oligomeric states are composed of cleaved and uncleaved particles, indicating that N-terminal processing is not critical for dimerization. A 3.5 Å cryo-EM structure provides details of Mpro N-terminal cleavage outside the constrains of crystal environment. We show that different classes of inhibitors shift the balance between oligomeric states. While non-covalent inhibitor MAT-POS-e194df51-1 prevents dimerization, the covalent inhibitor nirmatrelvir induces the conversion of monomers into dimers, even with intact N-termini. Our data indicates that the Mpro dimerization is triggered by induced fit due to covalent linkage during substrate processing rather than the N-terminal processing.	Mar 2023

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Krios II-Titan Krios II at Diamond

An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition