Giuseppe
Emeritus
[Source: Antiviral Research, full page: (LINK). Abstract, edited.]
Antiviral Research, Available online 8 October 2013
Review
Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research
Graham Simmons<SUP>a</SUP>, Pawel Zmora<SUP>b</SUP><SUP>, </SUP> Stefanie Gierer<SUP>b</SUP>, Adeline Heurich<SUP>b</SUP>, Stefan P?hlmann<SUP>b</SUP>
<SUP></SUP>
<SUP>a</SUP> Blood Systems Research Institute, 270 Masonic Ave, San Francisco, CA 94118, United States of America <SUP>b</SUP> Infection Biology Unit, German Primate Center, Kellnerweg 4, 37077 G?ttingen, Germany
Available online 8 October 2013
Highlights
Abstract
The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on ??From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.??
Keywords: SARS; Cathepsin L; TMPRSS2; Spike protein; Protease; MERS
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Corresponding author. Tel.: +49 551 3851 150; fax: +49 551 3851 184.
Copyright ? 2013 Published by Elsevier B.V.
Note to users: Accepted manuscripts are Articles in Press that have been peer reviewed and accepted for publication by the Editorial Board of this journal. They have not yet been copy edited and/or formatted in the journal house style, and may not yet have the full ScienceDirect functionality, e.g., supplementary files may still need to be added, links to references may not resolve yet etc. The text could still change before final publication.
Although accepted manuscripts do not have all bibliographic details available yet, they can already be cited using the year of online publication and the DOI, as follows: author(s), article title, journal (year), DOI. Please consult the journal's reference style for the exact appearance of these elements, abbreviation of journal names and use of punctuation.
When the final article is assigned to an issue of the journal, the Article in Press version will be removed and the final version will appear in the associated published issue of the journal. The date the article was first made available online will be carried over.
Copyright ? 2013 Elsevier B.V. All rights reserved. ScienceDirect? is a registered trademark of Elsevier B.V.
http://dx.doi.org/10.1016/j.antiviral.2013.09.028
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Antiviral Research, Available online 8 October 2013
Review
Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research
Graham Simmons<SUP>a</SUP>, Pawel Zmora<SUP>b</SUP><SUP>, </SUP> Stefanie Gierer<SUP>b</SUP>, Adeline Heurich<SUP>b</SUP>, Stefan P?hlmann<SUP>b</SUP>
<SUP></SUP>
<SUP>a</SUP> Blood Systems Research Institute, 270 Masonic Ave, San Francisco, CA 94118, United States of America <SUP>b</SUP> Infection Biology Unit, German Primate Center, Kellnerweg 4, 37077 G?ttingen, Germany
Available online 8 October 2013
Highlights
- Host cell proteases activate the spike-protein of the SARS-coronavirus.
- Activation is essential for viral infectivity and a potential target for intervention.
- Cathepsin L activates the spike-protein in host cell endosomes.
- TMPRSS2 activates the spike-protein at the plasma membrane.
- SARS- and MERS-coronavirus exploit the same proteases for activation.
Abstract
The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on ??From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.??
Keywords: SARS; Cathepsin L; TMPRSS2; Spike protein; Protease; MERS
__
Corresponding author. Tel.: +49 551 3851 150; fax: +49 551 3851 184.
Copyright ? 2013 Published by Elsevier B.V.
Note to users: Accepted manuscripts are Articles in Press that have been peer reviewed and accepted for publication by the Editorial Board of this journal. They have not yet been copy edited and/or formatted in the journal house style, and may not yet have the full ScienceDirect functionality, e.g., supplementary files may still need to be added, links to references may not resolve yet etc. The text could still change before final publication.
Although accepted manuscripts do not have all bibliographic details available yet, they can already be cited using the year of online publication and the DOI, as follows: author(s), article title, journal (year), DOI. Please consult the journal's reference style for the exact appearance of these elements, abbreviation of journal names and use of punctuation.
When the final article is assigned to an issue of the journal, the Article in Press version will be removed and the final version will appear in the associated published issue of the journal. The date the article was first made available online will be carried over.
Copyright ? 2013 Elsevier B.V. All rights reserved. ScienceDirect? is a registered trademark of Elsevier B.V.
http://dx.doi.org/10.1016/j.antiviral.2013.09.028
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