Antiviral cyclic peptides targeting the main protease of SARS-CoV-2
Field | Value | Language |
dc.contributor.author | Johansen-Leete, Jason | en_AU |
dc.contributor.author | Ullrich, Sven | en_AU |
dc.contributor.author | Fry, Sarah E. | en_AU |
dc.contributor.author | Frkic, Rebecca | en_AU |
dc.contributor.author | Bedding, Max J. | en_AU |
dc.contributor.author | Aggarwal, Anupriya | en_AU |
dc.contributor.author | Ashhurst, Anneliese S. | en_AU |
dc.contributor.author | Ekanayake, Kasuni B. | en_AU |
dc.contributor.author | Mahawaththa, Mithun C. | en_AU |
dc.contributor.author | Sasi, Vishnu M. | en_AU |
dc.contributor.author | Luedtke, Stephanie | en_AU |
dc.contributor.author | Ford, Daniel J. | en_AU |
dc.contributor.author | O'Donoghue, Anthony J. | en_AU |
dc.contributor.author | Passioura, Toby | en_AU |
dc.contributor.author | Larance, Mark | en_AU |
dc.contributor.author | Otting, Gottfried | en_AU |
dc.contributor.author | Turville, Stuart | en_AU |
dc.contributor.author | Jackson, Colin J. | en_AU |
dc.contributor.author | Nitsche, Christoph | en_AU |
dc.contributor.author | Payne, Richard J. | en_AU |
dc.date.accessioned | 2022-07-04T00:45:42Z | |
dc.date.available | 2022-07-04T00:45:42Z | |
dc.date.issued | 2022 | |
dc.identifier.uri | https://hdl.handle.net/2123/28987 | |
dc.description.abstract | Antivirals 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.iso | en | en_AU |
dc.subject | COVID-19 | en_AUI |
dc.subject | Coronavirus | en_AUI |
dc.title | Antiviral cyclic peptides targeting the main protease of SARS-CoV-2 | en_AU |
dc.type | Article | en_AU |
dc.identifier.doi | 10.1039/d1sc06750h | |
dc.relation.other | ICRP - International Cancer Research Partnership | en_AU |
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