ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea

Abstract 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 collapse around the world. Effective treatments to m...

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Autores principales:	Thang L. Pham, Jiucheng He, Azucena H. Kakazu, Jorgelina Calandria, Khanh V. Do, Robert Nshimiyimana, Ting F. Lam, Nicos A. Petasis, Haydee E. P. Bazan, Nicolas G. Bazan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dc09ab38615546c8b5b456b05f0cc312
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spelling	oai:doaj.org-article:dc09ab38615546c8b5b456b05f0cc3122021-12-02T17:40:01ZELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea10.1038/s41598-021-92293-x2045-2322https://doaj.org/article/dc09ab38615546c8b5b456b05f0cc3122021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92293-xhttps://doaj.org/toc/2045-2322Abstract 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 collapse around the world. Effective treatments to mitigate this viral 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 (HCEC) in culture challenged with IFNγ as models of the eye surface 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). We found that the lipid mediators, elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i) decreased the expression of the ACE2 receptor, furin, and integrins in damaged corneas or IFNγ-stimulated HCEC. There was also a concomitant decrease in the binding of Spike RBD with the lipid treatments. Using RNA-seq analysis, we uncovered that the lipid mediators also attenuated the expression of pro-inflammatoy cytokines participating in hyper-inflammation and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to open therapeutic avenues to counteract virus attachment and entrance to the body.Thang L. PhamJiucheng HeAzucena H. KakazuJorgelina CalandriaKhanh V. DoRobert NshimiyimanaTing F. LamNicos A. PetasisHaydee E. P. BazanNicolas G. BazanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thang L. Pham Jiucheng He Azucena H. Kakazu Jorgelina Calandria Khanh V. Do Robert Nshimiyimana Ting F. Lam Nicos A. Petasis Haydee E. P. Bazan Nicolas G. Bazan ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea
description	Abstract 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 collapse around the world. Effective treatments to mitigate this viral 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 (HCEC) in culture challenged with IFNγ as models of the eye surface 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). We found that the lipid mediators, elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i) decreased the expression of the ACE2 receptor, furin, and integrins in damaged corneas or IFNγ-stimulated HCEC. There was also a concomitant decrease in the binding of Spike RBD with the lipid treatments. Using RNA-seq analysis, we uncovered that the lipid mediators also attenuated the expression of pro-inflammatoy cytokines participating in hyper-inflammation and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to open therapeutic avenues to counteract virus attachment and entrance to the body.
format	article
author	Thang L. Pham Jiucheng He Azucena H. Kakazu Jorgelina Calandria Khanh V. Do Robert Nshimiyimana Ting F. Lam Nicos A. Petasis Haydee E. P. Bazan Nicolas G. Bazan
author_facet	Thang L. Pham Jiucheng He Azucena H. Kakazu Jorgelina Calandria Khanh V. Do Robert Nshimiyimana Ting F. Lam Nicos A. Petasis Haydee E. P. Bazan Nicolas G. Bazan
author_sort	Thang L. Pham
title	ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea
title_short	ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea
title_full	ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea
title_fullStr	ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea
title_full_unstemmed	ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea
title_sort	elv-n32 and rvd6 isomer decrease pro-inflammatory cytokines, senescence programming, ace2 and sars-cov-2-spike protein rbd binding in injured cornea
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dc09ab38615546c8b5b456b05f0cc312
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ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea

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