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Presence of a SARS-COV-2 protein enhances Amyloid Formation of Serum Amyloid A
A marker for the severeness and disease progress of COVID-19 is overexpression of serum amyloid A (SAA) to levels that in other diseases are associated with a risk for SAA amyloidosis. In order to understand whether SAA amyloidosis could also be a long-term risk of SARS-COV-2 infections we have used...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cold Spring Harbor Laboratory
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142650/ https://www.ncbi.nlm.nih.gov/pubmed/34031653 http://dx.doi.org/10.1101/2021.05.18.444723 |
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author | Jana, Asis K. Greenwood, Augustus B. Hansmann, Ulrich H. E. |
author_facet | Jana, Asis K. Greenwood, Augustus B. Hansmann, Ulrich H. E. |
author_sort | Jana, Asis K. |
collection | PubMed |
description | A marker for the severeness and disease progress of COVID-19 is overexpression of serum amyloid A (SAA) to levels that in other diseases are associated with a risk for SAA amyloidosis. In order to understand whether SAA amyloidosis could also be a long-term risk of SARS-COV-2 infections we have used long all-atom molecular dynamic simulations to study the effect of a SARS-COV-2 protein segment on SAA amyloid formation. Sampling over 40 μs we find that presence of the nine-residue segment SK9, located at the C-terminus of the Envelope protein, increases the propensity for SAA fibril formation by three mechanisms: it reduces the stability of the lipid-transporting hexamer shifting the equilibrium toward monomers, it increases the frequency of aggregation-prone configurations in the resulting chains, and it raises the stability of SAA fibrils. Our results therefore suggest that SAA amyloidosis and related pathologies may be a long-term risk of SARS-COV-2 infections. |
format | Online Article Text |
id | pubmed-8142650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-81426502021-05-25 Presence of a SARS-COV-2 protein enhances Amyloid Formation of Serum Amyloid A Jana, Asis K. Greenwood, Augustus B. Hansmann, Ulrich H. E. bioRxiv Article A marker for the severeness and disease progress of COVID-19 is overexpression of serum amyloid A (SAA) to levels that in other diseases are associated with a risk for SAA amyloidosis. In order to understand whether SAA amyloidosis could also be a long-term risk of SARS-COV-2 infections we have used long all-atom molecular dynamic simulations to study the effect of a SARS-COV-2 protein segment on SAA amyloid formation. Sampling over 40 μs we find that presence of the nine-residue segment SK9, located at the C-terminus of the Envelope protein, increases the propensity for SAA fibril formation by three mechanisms: it reduces the stability of the lipid-transporting hexamer shifting the equilibrium toward monomers, it increases the frequency of aggregation-prone configurations in the resulting chains, and it raises the stability of SAA fibrils. Our results therefore suggest that SAA amyloidosis and related pathologies may be a long-term risk of SARS-COV-2 infections. Cold Spring Harbor Laboratory 2021-07-21 /pmc/articles/PMC8142650/ /pubmed/34031653 http://dx.doi.org/10.1101/2021.05.18.444723 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Jana, Asis K. Greenwood, Augustus B. Hansmann, Ulrich H. E. Presence of a SARS-COV-2 protein enhances Amyloid Formation of Serum Amyloid A |
title | Presence of a SARS-COV-2 protein enhances Amyloid Formation of Serum Amyloid A |
title_full | Presence of a SARS-COV-2 protein enhances Amyloid Formation of Serum Amyloid A |
title_fullStr | Presence of a SARS-COV-2 protein enhances Amyloid Formation of Serum Amyloid A |
title_full_unstemmed | Presence of a SARS-COV-2 protein enhances Amyloid Formation of Serum Amyloid A |
title_short | Presence of a SARS-COV-2 protein enhances Amyloid Formation of Serum Amyloid A |
title_sort | presence of a sars-cov-2 protein enhances amyloid formation of serum amyloid a |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142650/ https://www.ncbi.nlm.nih.gov/pubmed/34031653 http://dx.doi.org/10.1101/2021.05.18.444723 |
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