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SARS‐CoV‐2 infection remodels the host protein thermal stability landscape
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a global threat to human health and has compromised economic stability. In addition to the development of an effective vaccine, it is imperative to understand how SARS‐CoV‐2 hijacks host cellular machineries on a system‐wide scale s...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885171/ https://www.ncbi.nlm.nih.gov/pubmed/33590968 http://dx.doi.org/10.15252/msb.202010188 |
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author | Selkrig, Joel Stanifer, Megan Mateus, André Mitosch, Karin Barrio‐Hernandez, Inigo Rettel, Mandy Kim, Heeyoung Voogdt, Carlos G P Walch, Philipp Kee, Carmon Kurzawa, Nils Stein, Frank Potel, Clément Jarzab, Anna Kuster, Bernhard Bartenschlager, Ralf Boulant, Steeve Beltrao, Pedro Typas, Athanasios Savitski, Mikhail M |
author_facet | Selkrig, Joel Stanifer, Megan Mateus, André Mitosch, Karin Barrio‐Hernandez, Inigo Rettel, Mandy Kim, Heeyoung Voogdt, Carlos G P Walch, Philipp Kee, Carmon Kurzawa, Nils Stein, Frank Potel, Clément Jarzab, Anna Kuster, Bernhard Bartenschlager, Ralf Boulant, Steeve Beltrao, Pedro Typas, Athanasios Savitski, Mikhail M |
author_sort | Selkrig, Joel |
collection | PubMed |
description | The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a global threat to human health and has compromised economic stability. In addition to the development of an effective vaccine, it is imperative to understand how SARS‐CoV‐2 hijacks host cellular machineries on a system‐wide scale so that potential host‐directed therapies can be developed. In situ proteome‐wide abundance and thermal stability measurements using thermal proteome profiling (TPP) can inform on global changes in protein activity. Here we adapted TPP to high biosafety conditions amenable to SARS‐CoV‐2 handling. We discovered pronounced temporal alterations in host protein thermostability during infection, which converged on cellular processes including cell cycle, microtubule and RNA splicing regulation. Pharmacological inhibition of host proteins displaying altered thermal stability or abundance during infection suppressed SARS‐CoV‐2 replication. Overall, this work serves as a framework for expanding TPP workflows to globally important human pathogens that require high biosafety containment and provides deeper resolution into the molecular changes induced by SARS‐CoV‐2 infection. |
format | Online Article Text |
id | pubmed-7885171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78851712021-02-26 SARS‐CoV‐2 infection remodels the host protein thermal stability landscape Selkrig, Joel Stanifer, Megan Mateus, André Mitosch, Karin Barrio‐Hernandez, Inigo Rettel, Mandy Kim, Heeyoung Voogdt, Carlos G P Walch, Philipp Kee, Carmon Kurzawa, Nils Stein, Frank Potel, Clément Jarzab, Anna Kuster, Bernhard Bartenschlager, Ralf Boulant, Steeve Beltrao, Pedro Typas, Athanasios Savitski, Mikhail M Mol Syst Biol Articles The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a global threat to human health and has compromised economic stability. In addition to the development of an effective vaccine, it is imperative to understand how SARS‐CoV‐2 hijacks host cellular machineries on a system‐wide scale so that potential host‐directed therapies can be developed. In situ proteome‐wide abundance and thermal stability measurements using thermal proteome profiling (TPP) can inform on global changes in protein activity. Here we adapted TPP to high biosafety conditions amenable to SARS‐CoV‐2 handling. We discovered pronounced temporal alterations in host protein thermostability during infection, which converged on cellular processes including cell cycle, microtubule and RNA splicing regulation. Pharmacological inhibition of host proteins displaying altered thermal stability or abundance during infection suppressed SARS‐CoV‐2 replication. Overall, this work serves as a framework for expanding TPP workflows to globally important human pathogens that require high biosafety containment and provides deeper resolution into the molecular changes induced by SARS‐CoV‐2 infection. John Wiley and Sons Inc. 2021-02-16 /pmc/articles/PMC7885171/ /pubmed/33590968 http://dx.doi.org/10.15252/msb.202010188 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Selkrig, Joel Stanifer, Megan Mateus, André Mitosch, Karin Barrio‐Hernandez, Inigo Rettel, Mandy Kim, Heeyoung Voogdt, Carlos G P Walch, Philipp Kee, Carmon Kurzawa, Nils Stein, Frank Potel, Clément Jarzab, Anna Kuster, Bernhard Bartenschlager, Ralf Boulant, Steeve Beltrao, Pedro Typas, Athanasios Savitski, Mikhail M SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_full | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_fullStr | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_full_unstemmed | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_short | SARS‐CoV‐2 infection remodels the host protein thermal stability landscape |
title_sort | sars‐cov‐2 infection remodels the host protein thermal stability landscape |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885171/ https://www.ncbi.nlm.nih.gov/pubmed/33590968 http://dx.doi.org/10.15252/msb.202010188 |
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