Cargando…

Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2

While there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it’s unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it’s unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently...

Descripción completa

Detalles Bibliográficos
Autores principales: Brady, Molly, McQuaid, Conor, Solorzano, Alexander, Johnson, Angelique, Combs, Abigail, Venkatraman, Chethana, Rahman, Akib, Leyva, Hannah, Kwok, Wing-Chi Edmund, Wood, Ronald W., Deane, Rashid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609008/
https://www.ncbi.nlm.nih.gov/pubmed/34811493
http://dx.doi.org/10.1038/s42003-021-02856-x
_version_ 1784602844353003520
author Brady, Molly
McQuaid, Conor
Solorzano, Alexander
Johnson, Angelique
Combs, Abigail
Venkatraman, Chethana
Rahman, Akib
Leyva, Hannah
Kwok, Wing-Chi Edmund
Wood, Ronald W.
Deane, Rashid
author_facet Brady, Molly
McQuaid, Conor
Solorzano, Alexander
Johnson, Angelique
Combs, Abigail
Venkatraman, Chethana
Rahman, Akib
Leyva, Hannah
Kwok, Wing-Chi Edmund
Wood, Ronald W.
Deane, Rashid
author_sort Brady, Molly
collection PubMed
description While there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it’s unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it’s unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently labeled SP-NIRF to study viral behavior, using an in vivo dynamic imaging system and ex in vivo tissue analysis, in young mice. We found a SP body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. SP uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or CSF. Thus, the brain vascular barriers were effective in restricting the entry of SP into brain parenchyma in young healthy mice. While both anti-ACE2 and anti-SP antibodies suppressed SP biodistribution and organ uptake, anti-SP antibody was more effective. By extension, our data support the efficacy of these antibodies on SARS-CoV-2 multiorgan tropism, which could determine COVID-19 organ-specific outcomes.
format Online
Article
Text
id pubmed-8609008
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-86090082021-12-01 Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2 Brady, Molly McQuaid, Conor Solorzano, Alexander Johnson, Angelique Combs, Abigail Venkatraman, Chethana Rahman, Akib Leyva, Hannah Kwok, Wing-Chi Edmund Wood, Ronald W. Deane, Rashid Commun Biol Article While there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it’s unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it’s unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently labeled SP-NIRF to study viral behavior, using an in vivo dynamic imaging system and ex in vivo tissue analysis, in young mice. We found a SP body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. SP uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or CSF. Thus, the brain vascular barriers were effective in restricting the entry of SP into brain parenchyma in young healthy mice. While both anti-ACE2 and anti-SP antibodies suppressed SP biodistribution and organ uptake, anti-SP antibody was more effective. By extension, our data support the efficacy of these antibodies on SARS-CoV-2 multiorgan tropism, which could determine COVID-19 organ-specific outcomes. Nature Publishing Group UK 2021-11-22 /pmc/articles/PMC8609008/ /pubmed/34811493 http://dx.doi.org/10.1038/s42003-021-02856-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Brady, Molly
McQuaid, Conor
Solorzano, Alexander
Johnson, Angelique
Combs, Abigail
Venkatraman, Chethana
Rahman, Akib
Leyva, Hannah
Kwok, Wing-Chi Edmund
Wood, Ronald W.
Deane, Rashid
Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
title Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
title_full Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
title_fullStr Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
title_full_unstemmed Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
title_short Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
title_sort spike protein multiorgan tropism suppressed by antibodies targeting sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609008/
https://www.ncbi.nlm.nih.gov/pubmed/34811493
http://dx.doi.org/10.1038/s42003-021-02856-x
work_keys_str_mv AT bradymolly spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT mcquaidconor spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT solorzanoalexander spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT johnsonangelique spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT combsabigail spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT venkatramanchethana spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT rahmanakib spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT leyvahannah spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT kwokwingchiedmund spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT woodronaldw spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2
AT deanerashid spikeproteinmultiorgantropismsuppressedbyantibodiestargetingsarscov2