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SARS-CoV-2 uses major endothelial integrin αvβ3 to cause vascular dysregulation in-vitro during COVID-19

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posted on 16.07.2021, 16:14 by Danielle NaderDanielle Nader, Nicola Fletcher, Gerard CurleyGerard Curley, Steven KerriganSteven Kerrigan
The unprecedented global COVID-19 pandemic has prompted a desperate international effort to accelerate the development of anti-viral candidates. For unknown reasons, COVID-19 infections are associated with adverse cardiovascular complications, implicating that vascular endothelial cells are essential in viral propagation. The etiological pathogen, SARS-CoV-2, has a higher reproductive number and infection rate than its predecessors, indicating it possesses novel characteristics that infers enhanced transmissibility. A unique K403R spike protein substitution encodes an Arg-Gly-Asp (RGD) motif, introducing a potential role for RGD-binding host integrins. Integrin αVβ3 is widely expressed across the host, particularly in the endothelium, which acts as the final barrier before microbial entry into the bloodstream. This mutagenesis creates an additional binding site, which may be sufficient to increase SARS-CoV-2 pathogenicity. Here, we investigate how SARS-CoV-2 passes from the epithelium to endothelium, the effects of αVβ3 antagonist, Cilengitide, on viral adhesion, vasculature permeability and leakage, and also report on a simulated interaction between the viral and host protein in-silico.

Funding

A novel method for treating sepsis early by targeting the vascular endothelium | Funder: Enterprise Ireland | Grant ID: CF 2017 0684-P

Anti-integrin therapy in the treatment of COVID-19. | Funder: 3M & Global Giving

A potential role for cilengitide in the treatment of COVID-19 | Funder: Enterprise Ireland | Grant ID: SI 2020 3044

History

Comments

The original article is available at https://journals.plos.org

Published Citation

Nader D, Fletcher N, Curley GF, Kerrigan SW. SARS-CoV-2 uses major endothelial integrin αvβ3 to cause vascular dysregulation in-vitro during COVID-19. PLoS One. 2021;16(6):e0253347.

Publication Date

23 June 2021

PubMed ID

34161337

Department/Unit

  • Anaesthetics and Critical Care
  • Beaumont Hospital
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Biomaterials and Regenerative Medicine
  • Vascular Biology
  • Immunity, Infection and Inflammation

Publisher

Public Library of Science (PLoS)

Version

  • Published Version (Version of Record)