Stapled ACE2 peptidomimetics designed to target the SARS-CoV-2 spike protein do not prevent virus internalisation

Morgan, D. C. et al. (2021) Stapled ACE2 peptidomimetics designed to target the SARS-CoV-2 spike protein do not prevent virus internalisation. Peptide Science, 113(4), e24217. (doi: 10.1002/pep2.24217) (PMID:33615115) (PMCID:PMC7883042)

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Abstract

COVID‐19 is caused by a novel coronavirus called severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Virus cell entry is mediated through a protein‐protein interaction (PPI) between the SARS‐CoV‐2 spike protein and angiotensin‐converting enzyme 2 (ACE2). A series of stapled peptide ACE2 peptidomimetics based on the ACE2 interaction motif were designed to bind the coronavirus S‐protein RBD and inhibit binding to the human ACE2 receptor. The peptidomimetics were assessed for antiviral activity in an array of assays including a neutralization pseudovirus assay, immunofluorescence (IF) assay and in‐vitro fluorescence polarization (FP) assay. However, none of the peptidomimetics showed activity in these assays, suggesting that an enhanced binding interface is required to outcompete ACE2 for S‐protein RBD binding and prevent virus internalization.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bhella, Professor David and Turnbull, Dr Matthew and Tejeda, Dr Rer Nat Gonzalo and Baillie, Professor George and Logan, Miss Nicola and Willett, Professor Brian and Tobin, Andrew and Mahindra, Dr Amit and Morgan, Miss Danielle and Blair, Dr Connor and Herbert, Miss Imogen and Lieber, Mr Gauthier and Jamieson, Dr Andrew and Smith, Dr Brian and Morris, Dr Caroline
Authors: Morgan, D. C., Morris, C., Mahindra, A., Blair, C. M., Tejeda, G., Herbert, I., Turnbull, M. L., Lieber, G., Willett, B. J., Logan, N., Smith, B., Tobin, A. B., Bhella, D., Baillie, G. S., and Jamieson, A. G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Science and Engineering > School of Chemistry
Journal Name:Peptide Science
Publisher:Wiley
ISSN:2475-8817
ISSN (Online):2475-8817
Published Online:08 January 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Peptide Science 113(4): e24217
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
305807Substrate Peptidomimetic Inhibitors (SPIs) of the COP9 signalosomeAndrew JamiesonEngineering and Physical Sciences Research Council (EPSRC)EP/N034260/2Chemistry
172865EPSRC DTP 16/17 and 17/18Tania GalabovaEngineering and Physical Sciences Research Council (EPSRC)EP/N509668/1Research and Innovation Services
305200DTP 2018-19 University of GlasgowMary Beth KneafseyEngineering and Physical Sciences Research Council (EPSRC)EP/R513222/1MVLS - Graduate School