Show simple item record

FieldValueLanguage
dc.contributor.authorJohansen-Leete, Jasonen_AU
dc.contributor.authorUllrich, Svenen_AU
dc.contributor.authorFry, Sarah E.en_AU
dc.contributor.authorFrkic, Rebeccaen_AU
dc.contributor.authorBedding, Max J.en_AU
dc.contributor.authorAggarwal, Anupriyaen_AU
dc.contributor.authorAshhurst, Anneliese S.en_AU
dc.contributor.authorEkanayake, Kasuni B.en_AU
dc.contributor.authorMahawaththa, Mithun C.en_AU
dc.contributor.authorSasi, Vishnu M.en_AU
dc.contributor.authorLuedtke, Stephanieen_AU
dc.contributor.authorFord, Daniel J.en_AU
dc.contributor.authorO'Donoghue, Anthony J.en_AU
dc.contributor.authorPassioura, Tobyen_AU
dc.contributor.authorLarance, Marken_AU
dc.contributor.authorOtting, Gottfrieden_AU
dc.contributor.authorTurville, Stuarten_AU
dc.contributor.authorJackson, Colin J.en_AU
dc.contributor.authorNitsche, Christophen_AU
dc.contributor.authorPayne, Richard J.en_AU
dc.date.accessioned2022-07-04T00:45:42Z
dc.date.available2022-07-04T00:45:42Z
dc.date.issued2022
dc.identifier.urihttps://hdl.handle.net/2123/28987
dc.description.abstractAntivirals that specifically target SARS-CoV-2 are needed to control the COVID-19 pandemic. The main protease (Mpro) is essential for SARS-CoV-2 replication and is an attractive target for antiviral development. Here we report the use of the Random nonstandard Peptide Integrated Discovery (RaPID) mRNA display on a chemically cross-linked SARS-CoV-2 Mpro dimer, which yielded several high-affinity thioether-linked cyclic peptide inhibitors of the protease. Structural analysis of Mpro complexed with a selenoether analogue of the highest-affinity peptide revealed key binding interactions, including glutamine and leucine residues in sites S1 and S2, respectively, and a binding epitope straddling both protein chains in the physiological dimer. Several of these Mpro peptide inhibitors possessed antiviral activity against SARS-CoV-2 in vitro with EC50 values in the low micromolar range. These cyclic peptides serve as a foundation for the development of much needed antivirals that specifically target SARS-CoV-2.en_AU
dc.language.isoenen_AU
dc.subjectCOVID-19en_AUI
dc.subjectCoronavirusen_AUI
dc.titleAntiviral cyclic peptides targeting the main protease of SARS-CoV-2en_AU
dc.typeArticleen_AU
dc.identifier.doi10.1039/d1sc06750h
dc.relation.otherICRP - International Cancer Research Partnershipen_AU


Show simple item record

Associated file/s

There are no files associated with this item.

Associated collections

Show simple item record

There are no previous versions of the item available.