Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1783515404149194752 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7122371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hoffmannmarkus primingtimehowcellularproteasesarmcoronavirusspikeproteins AT hofmannwinklerheike primingtimehowcellularproteasesarmcoronavirusspikeproteins AT pohlmannstefan primingtimehowcellularproteasesarmcoronavirusspikeproteins |