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Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins

Coronaviruses are enveloped RNA viruses that infect mammals and birds. Infection of humans with globally circulating human coronaviruses is associated with the common cold. In contrast, transmission of animal coronaviruses to humans can result in severe disease: The severe acute respiratory syndrome...

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Autores principales: Hoffmann, Markus, Hofmann-Winkler, Heike, Pöhlmann, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122371/
http://dx.doi.org/10.1007/978-3-319-75474-1_4
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author Hoffmann, Markus
Hofmann-Winkler, Heike
Pöhlmann, Stefan
author_facet Hoffmann, Markus
Hofmann-Winkler, Heike
Pöhlmann, Stefan
author_sort Hoffmann, Markus
collection PubMed
description Coronaviruses are enveloped RNA viruses that infect mammals and birds. Infection of humans with globally circulating human coronaviruses is associated with the common cold. In contrast, transmission of animal coronaviruses to humans can result in severe disease: The severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) are responsible for hundreds of deaths in Asia and the Middle East, respectively, and are both caused by members of the genus Betacoronavirus, SARS-CoV, and MERS-CoV that were zoonotically transmitted from an animal host to humans. At present, neither vaccines nor specific treatment is available to combat coronavirus infection in humans, and novel antiviral strategies are urgently sought. The viral spike protein (S) mediates the first essential step in coronavirus infection, viral entry into target cells. For this, the S protein critically depends on priming by host cell proteases, and the responsible enzymes are potential targets for antiviral intervention. Recent studies revealed that the endosomal cysteine protease cathepsin L and the serine proteases furin and TMPRSS2 prime the S proteins of SARS-CoV and MERS-CoV and provided evidence that successive S protein cleavage at two sites is required for S protein priming. Moreover, mechanisms that control protease choice were unraveled, and insights were obtained into which enzyme promotes viral spread in the host. Here, we will provide basic information on S protein function and proteolytic priming, and we will then discuss recent progress in our understanding of the priming of the S proteins of SARS-CoV and MERS-CoV.
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spelling pubmed-71223712020-04-06 Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins Hoffmann, Markus Hofmann-Winkler, Heike Pöhlmann, Stefan Activation of Viruses by Host Proteases Article Coronaviruses are enveloped RNA viruses that infect mammals and birds. Infection of humans with globally circulating human coronaviruses is associated with the common cold. In contrast, transmission of animal coronaviruses to humans can result in severe disease: The severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) are responsible for hundreds of deaths in Asia and the Middle East, respectively, and are both caused by members of the genus Betacoronavirus, SARS-CoV, and MERS-CoV that were zoonotically transmitted from an animal host to humans. At present, neither vaccines nor specific treatment is available to combat coronavirus infection in humans, and novel antiviral strategies are urgently sought. The viral spike protein (S) mediates the first essential step in coronavirus infection, viral entry into target cells. For this, the S protein critically depends on priming by host cell proteases, and the responsible enzymes are potential targets for antiviral intervention. Recent studies revealed that the endosomal cysteine protease cathepsin L and the serine proteases furin and TMPRSS2 prime the S proteins of SARS-CoV and MERS-CoV and provided evidence that successive S protein cleavage at two sites is required for S protein priming. Moreover, mechanisms that control protease choice were unraveled, and insights were obtained into which enzyme promotes viral spread in the host. Here, we will provide basic information on S protein function and proteolytic priming, and we will then discuss recent progress in our understanding of the priming of the S proteins of SARS-CoV and MERS-CoV. 2018-02-16 /pmc/articles/PMC7122371/ http://dx.doi.org/10.1007/978-3-319-75474-1_4 Text en © Springer International Publishing AG, part of Springer Nature 2018 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Hoffmann, Markus
Hofmann-Winkler, Heike
Pöhlmann, Stefan
Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins
title Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins
title_full Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins
title_fullStr Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins
title_full_unstemmed Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins
title_short Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins
title_sort priming time: how cellular proteases arm coronavirus spike proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122371/
http://dx.doi.org/10.1007/978-3-319-75474-1_4
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