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Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic tall around the world. Effective treatments to mitigate this...

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Autores principales: Pham, Thang L., He, Jiucheng, Kakazu, Azucena H., Calandria, Jorgelina, Do, Khanh V., Nshimiyimana, Robert, Petasis, Nicos A., Bazan, Haydee E.P., Bazan, Nicolas G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430585/
https://www.ncbi.nlm.nih.gov/pubmed/32818210
http://dx.doi.org/10.21203/rs.3.rs-55764/v1
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author Pham, Thang L.
He, Jiucheng
Kakazu, Azucena H.
Calandria, Jorgelina
Do, Khanh V.
Nshimiyimana, Robert
Petasis, Nicos A.
Bazan, Haydee E.P.
Bazan, Nicolas G.
author_facet Pham, Thang L.
He, Jiucheng
Kakazu, Azucena H.
Calandria, Jorgelina
Do, Khanh V.
Nshimiyimana, Robert
Petasis, Nicos A.
Bazan, Haydee E.P.
Bazan, Nicolas G.
author_sort Pham, Thang L.
collection PubMed
description The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic tall around the world. Effective treatments to mitigate this virus infection are needed. Since the eye is a route of virus entrance, we use an in vivo rat model of corneal inflammation as well as human corneal epithelial cells in culture challenged with IFNγ to study this issue. We explore ways to block the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to angiotensin-converting enzyme 2 (ACE2). Elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i), among the lipid mediators studied, consistently decreased the expression of the ACE2 receptor, furin, and integrins in damaged corneas or IFNγ stimulated human corneal epithelial cells (HCEC). There was also a concomitant decrease in the binding of spike RBD with the lipid treatments. Concurrently, we uncovered that the lipid mediators also attenuated the expression of cytokines that participate in the cytokine storm, hyper-inflammation and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to opening therapeutic avenues for COVID-19 by counteracting virus attachment and entrance to the eye and other cells and the ensuing disruptions of homeostasis.
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spelling pubmed-74305852020-08-18 Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye Pham, Thang L. He, Jiucheng Kakazu, Azucena H. Calandria, Jorgelina Do, Khanh V. Nshimiyimana, Robert Petasis, Nicos A. Bazan, Haydee E.P. Bazan, Nicolas G. Res Sq Article The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic tall around the world. Effective treatments to mitigate this virus infection are needed. Since the eye is a route of virus entrance, we use an in vivo rat model of corneal inflammation as well as human corneal epithelial cells in culture challenged with IFNγ to study this issue. We explore ways to block the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to angiotensin-converting enzyme 2 (ACE2). Elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i), among the lipid mediators studied, consistently decreased the expression of the ACE2 receptor, furin, and integrins in damaged corneas or IFNγ stimulated human corneal epithelial cells (HCEC). There was also a concomitant decrease in the binding of spike RBD with the lipid treatments. Concurrently, we uncovered that the lipid mediators also attenuated the expression of cytokines that participate in the cytokine storm, hyper-inflammation and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to opening therapeutic avenues for COVID-19 by counteracting virus attachment and entrance to the eye and other cells and the ensuing disruptions of homeostasis. American Journal Experts 2020-08-11 /pmc/articles/PMC7430585/ /pubmed/32818210 http://dx.doi.org/10.21203/rs.3.rs-55764/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Pham, Thang L.
He, Jiucheng
Kakazu, Azucena H.
Calandria, Jorgelina
Do, Khanh V.
Nshimiyimana, Robert
Petasis, Nicos A.
Bazan, Haydee E.P.
Bazan, Nicolas G.
Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye
title Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye
title_full Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye
title_fullStr Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye
title_full_unstemmed Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye
title_short Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye
title_sort elovanoid-n32 or rvd6-isomer decrease ace2 and binding of s protein rbd after injury or infγ in the eye
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430585/
https://www.ncbi.nlm.nih.gov/pubmed/32818210
http://dx.doi.org/10.21203/rs.3.rs-55764/v1
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