Allosteric Inhibition of the SARS-CoV-2 Main Protease: Insights from Mass Spectrometry Based Assays*.

ABSTRACT: The SARS-CoV-2 main protease (M^pro ) cleaves along the two viral polypeptides to release non-structural proteins required for viral replication. M^Pro 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 M^pro . Analysis of the monomer/dimer equilibria reveals a dissociation constant of K_d =0.14±0.03 μM, indicating M^Pro 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 dis

SUBMITTER: El-Baba TJ 

PROVIDER: S-EPMC7461284 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature