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PXD036325

PXD036325 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA yeast-based system to study SARS-CoV-2 Mpro structure and to identify nirmatrelvir resistant mutations
DescriptionThe SARS-CoV-2 main protease (Mpro) is a major therapeutic target. The Mpro inhibitor, nirmatrelvir, is the antiviral component of Paxlovid, an orally available treatment for COVID-19. As Mpro inhibitor use increases, drug resistant mutations will likely emerge. We have established a non-pathogenic system, in which yeast growth serves as a proxy for Mpro activity, enabling rapid identification of mutants with altered enzymatic activity and drug sensitivity. The E166 residue is known to be a potential hot spot for drug resistance and yeast assays showed that an E166R substitution conferred strong nirmatrelvir resistance while an E166N mutation compromised activity. On the other hand, N142A and P132H mutations caused little to no change in drug response and activity. Standard enzymatic assays confirmed the yeast results. In turn, we solved the structures of Mpro E166R, and Mpro E166N, providing insights into how arginine may drive drug resistance while asparagine leads to reduced activity. The work presented here will help characterize novel resistant variants of Mpro that may arise as Mpro antivirals become more widely used.
HostingRepositoryPRIDE
AnnounceDate2023-08-08
AnnouncementXMLSubmission_2023-08-08_13:45:02.746.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD036325
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterPaulLanglais
SpeciesList scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; scientific name: Saccharomyces cerevisiae; NCBI TaxID: NCBITaxon:4932;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-26 07:18:57ID requested
12023-08-08 13:45:03announced
Publication List
10.6019/PXD036325;
Keyword List
ProteomeXchange project tag: Sars-cov-2, Covid-19
submitter keyword: COVID-19
Contact List
JohnChoy
contact affiliationDepartment of Biology, Catholic University of America
contact emailchoy@cua.edu
lab head
PaulLanglais
contact affiliationUniversity of Arizona
contact emaillanglais@deptofmed.arizona.edu
dataset submitter
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Dataset FTP location
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