|
?:abstract
|
-
The SARS‐CoV‐2 main protease (Mpro) cleaves along the two viral polypeptides to release non‐structural proteins required for viral replication MPro is an attractive target for antiviral therapies to combat the coronavirus‐2019 disease Here, we used native mass spectrometry to characterize the functional unit of Mpro Analysis of the monomer/dimer equilibria reveals a dissociation constant of Kd=0 14±0 03 μM, indicating MPro has a strong preference to dimerize in solution We characterized substrate turnover rates by following temporal changes in the enzyme‐substrate complexes, and screened small molecules, that bind distant from the active site, for their ability to modulate activity These compounds, including one proposed to disrupt the dimer, slow the rate of substrate processing by ≈35 % This information, together with analysis of the x‐ray crystal structures, provides a starting point for the development of more potent molecules that allosterically regulate MPro activity [ABSTRACT FROM AUTHOR] Copyright of Angewandte Chemie is the property of John Wiley & Sons, Inc and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder\'s express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )
|
![[This page as RDF]](https://research.tib.eu/covid-19/static/rdf-icon.gif){kind=icon}