Your browser doesn't support javascript.
loading
SARS-CoV-2 Spike protein promotes hyper-inflammatory response that can be ameliorated by Spike-antagonistic peptide and FDA-approved ER stress and MAP kinase inhibitors in vitro
Alan C-Y. Hsu; Guoqiang Wang; Andrew T. Reid; Punnam Chander Veerati; Prabuddha S. Pathinayake; Katie Daly; Jemma R. Mayall; Philip M. Hansbro; Jay C. Horvat; Fang Wang; Peter A. Wark.
Afiliación
  • Alan C-Y. Hsu; Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, New South Wales 2305, Australia
  • Guoqiang Wang; Department of Pathogen Biology, College of Basic Medical Science, Jilin University, Changchun 130021, China.
  • Andrew T. Reid; Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, New South Wales 2305, Australia
  • Punnam Chander Veerati; Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, New South Wales 2305, Australia
  • Prabuddha S. Pathinayake; Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, New South Wales 2305, Australia
  • Katie Daly; Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, New South Wales 2305, Australia
  • Jemma R. Mayall; Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, New South Wales 2305, Australia
  • Philip M. Hansbro; Centenary UTS Centre for Inflammation, Centenary Institute, New South Wales 2050, Australia
  • Jay C. Horvat; Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, New South Wales 2305, Australia
  • Fang Wang; Department of Pathogen Biology, College of Basic Medical Science, Jilin University, Changchun 130021, China.
  • Peter A. Wark; Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, New South Wales 2305, Australia
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-317818
ABSTRACT
SARS-CoV-2 infection causes an inflammatory cytokine storm and acute lung injury. Currently there are no effective antiviral and/or anti-inflammatory therapies. Here we demonstrate that 2019 SARS-CoV-2 spike protein subunit 1 (CoV2-S1) induces high levels of NF-{kappa}B activations, production of pro-inflammatory cytokines and mild epithelial damage, in human bronchial epithelial cells. CoV2-S1-induced NF-{kappa}B activation requires S1 interaction with human ACE2 receptor and early activation of endoplasmic reticulum (ER) stress, and associated unfolded protein response (UPR), and MAP kinase signalling pathways. We developed an antagonistic peptide that inhibits S1-ACE2 interaction and CoV2-S1-induced productions of pro-inflammatory cytokines. The existing FDA-approved ER stress inhibitor, 4-phenylburic acid (4-PBA), and MAP kinase inhibitors, trametinib and ulixertinib, ameliorated CoV2-S1-induced inflammation and epithelial damage. These novel data highlight the potentials of peptide-based antivirals for novel ACE2-utilising CoVs, while repurposing existing drugs may be used as treatments to dampen elevated inflammation and lung injury mediated by SARS-CoV-2.
Licencia
cc_by_nc_nd
Texto completo
Añadir a Mi BVS
Imprimir
XML
Buscar en Google
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo
Añadir a Mi BVS
Imprimir
XML
Buscar en Google
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2020 Tipo del documento: Preprint