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A decade after SARS: strategies for controlling emerging coronaviruses

Identifieur interne : 000568 ( Pmc/Curation ); précédent : 000567; suivant : 000569

A decade after SARS: strategies for controlling emerging coronaviruses

Auteurs : Rachel L. Graham ; Eric F. Donaldson ; Ralph S. Baric

Source :

RBID : PMC:5147543

Abstract

Key Points

Two highly pathogenic human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), have emerged in the past decade. The lack of any clinically approved antiviral treatments or vaccines for either virus emphasizes the importance of the design of effective therapeutics and preventives.

Bats have been implicated as reservoirs of both SARS-CoV and MERS-CoV as well as related viruses and other human coronaviruses (HCoVs), such as HCoV-229E and HCoV-NL63. The dispersion of bat species over much of the globe probably enhances their potential to act as reservoirs for pathogens, some of which are extremely virulent and potentially lethal to other animals and humans.

Multiple animal models for SARS-CoV infection exist, although mouse models have been the most thoroughly characterized. Mouse-adapted SARS-CoV is capable of causing pathology that is representative of human infections in both young and aged animals.

Small animal models for MERS-CoV infection have not yet been reported, although the possibility of further ongoing selection in the receptor-binding sequence in the spike protein or other sequences that are important for host specificity might contribute to this limitation. A mild disease phenotype that can include either localized or widespread pneumonia is observed in inoculated macaques.

Multiple vaccine strategies have been attempted with coronaviruses, mostly (but not exclusively) targeting the spike glycoprotein. Successful live-attenuated vaccines have utilized reverse genetic strategies to delete the envelope protein or inactivate the exonuclease activity of non-structural protein 14 (nsp14) .

MERS-CoV, similarly to SARS-CoV in 2003, has the potential to have a profound impact on the human population; however, its low penetrance thus far suggests that the virus might either ultimately fail to develop a niche in humans or it might still be adapting to human hosts and that the worst of its effects are yet to come.

Coronavirus phylogeny shows an incredible diversity in antigenic variants, which leads to limited cross-protection against infection with different strains, even within a phylogenetic subcluster. Consequently, the risk of introducing novel coronaviruses into naive human and animal populations remains high.

Supplementary information

The online version of this article (doi:10.1038/nrmicro3143) contains supplementary material, which is available to authorized users.


Url:
DOI: 10.1038/nrmicro3143
PubMed: 24217413
PubMed Central: 5147543

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PMC:5147543

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Rachel L. Graham
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<name sortKey="Tsushima, K" uniqKey="Tsushima K">K Tsushima</name>
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<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Nat Rev Microbiol</journal-id>
<journal-id journal-id-type="iso-abbrev">Nat. Rev. Microbiol</journal-id>
<journal-title-group>
<journal-title>Nature Reviews. Microbiology</journal-title>
</journal-title-group>
<issn pub-type="ppub">1740-1526</issn>
<issn pub-type="epub">1740-1534</issn>
<publisher>
<publisher-name>Nature Publishing Group UK</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">24217413</article-id>
<article-id pub-id-type="pmc">5147543</article-id>
<article-id pub-id-type="publisher-id">BFnrmicro3143</article-id>
<article-id pub-id-type="doi">10.1038/nrmicro3143</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>A decade after SARS: strategies for controlling emerging coronaviruses</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Graham</surname>
<given-names>Rachel L.</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<bio>
<p id="Par1">Rachel L. Graham received her Ph.D. in 2006 from Vanderbilt University, Nashville, Tennessee, USA, where she studied proteolytic processing and replication in coronavirus infections. She then began a postdoctoral fellowship and has continued as a research associate at the University of North Carolina at Chapel Hill, North Carolina, USA, where she is studying coronavirus pathogenesis and viral emergence.</p>
</bio>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Donaldson</surname>
<given-names>Eric F.</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<bio>
<p id="Par2">Eric F. Donaldson received his Ph.D. in 2008 from the University of North Carolina at Chapel Hill, North Carolina, USA. He has worked in the fields of viral metagenomics, coronavirus evolution and cross-species transmission, and norovirus evolution. He is interested in using computational approaches for modelling complex evolutionary problems and making predictions that can be tested empirically.</p>
</bio>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Baric</surname>
<given-names>Ralph S.</given-names>
</name>
<address>
<email>rbaric@email.unc.edu</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
<bio>
<p id="Par3">Ralph S. Baric received his Ph.D. in 1982 from North Carolina State University, Raleigh, North Carolina, USA. He is Professor of epidemiology at the University of North Carolina at Chapel Hill, North Carolina, USA, where his group studies virus evolution, cross-species transmission, replication, virus–host interactions, genetics and pathogenesis, using noroviruses, coronaviruses and flaviviruses as model systems.</p>
</bio>
</contrib>
<aff id="Aff1">
<label>1</label>
<institution-wrap>
<institution-id institution-id-type="GRID">grid.10698.36</institution-id>
<institution-id institution-id-type="ISNI">0000000122483208</institution-id>
<institution>Department of Epidemiology,</institution>
<institution>University of North Carolina at Chapel Hill,</institution>
</institution-wrap>
Chapel Hill, 27599 North Carolina USA</aff>
<aff id="Aff2">
<label>2</label>
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<institution-id institution-id-type="GRID">grid.10698.36</institution-id>
<institution-id institution-id-type="ISNI">0000000122483208</institution-id>
<institution>Department of Microbiology and Immunology,</institution>
<institution>University of North Carolina at Chapel Hill,</institution>
</institution-wrap>
Chapel Hill, 27599 North Carolina USA</aff>
</contrib-group>
<pub-date pub-type="epub">
<day>11</day>
<month>11</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="ppub">
<year>2013</year>
</pub-date>
<volume>11</volume>
<issue>12</issue>
<fpage>836</fpage>
<lpage>848</lpage>
<permissions>
<copyright-statement>© Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2013</copyright-statement>
<license>
<license-p>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.</license-p>
</license>
</permissions>
<abstract id="Abs1" abstract-type="KeyPoints">
<title>Key Points</title>
<p id="Par4">
<list list-type="bullet">
<list-item>
<p id="Par5">Two highly pathogenic human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), have emerged in the past decade. The lack of any clinically approved antiviral treatments or vaccines for either virus emphasizes the importance of the design of effective therapeutics and preventives.</p>
</list-item>
<list-item>
<p id="Par6">Bats have been implicated as reservoirs of both SARS-CoV and MERS-CoV as well as related viruses and other human coronaviruses (HCoVs), such as HCoV-229E and HCoV-NL63. The dispersion of bat species over much of the globe probably enhances their potential to act as reservoirs for pathogens, some of which are extremely virulent and potentially lethal to other animals and humans.</p>
</list-item>
<list-item>
<p id="Par7">Multiple animal models for SARS-CoV infection exist, although mouse models have been the most thoroughly characterized. Mouse-adapted SARS-CoV is capable of causing pathology that is representative of human infections in both young and aged animals.</p>
</list-item>
<list-item>
<p id="Par8">Small animal models for MERS-CoV infection have not yet been reported, although the possibility of further ongoing selection in the receptor-binding sequence in the spike protein or other sequences that are important for host specificity might contribute to this limitation. A mild disease phenotype that can include either localized or widespread pneumonia is observed in inoculated macaques.</p>
</list-item>
<list-item>
<p id="Par9">Multiple vaccine strategies have been attempted with coronaviruses, mostly (but not exclusively) targeting the spike glycoprotein. Successful live-attenuated vaccines have utilized reverse genetic strategies to delete the envelope protein or inactivate the exonuclease activity of non-structural protein 14 (nsp14) .</p>
</list-item>
<list-item>
<p id="Par10">MERS-CoV, similarly to SARS-CoV in 2003, has the potential to have a profound impact on the human population; however, its low penetrance thus far suggests that the virus might either ultimately fail to develop a niche in humans or it might still be adapting to human hosts and that the worst of its effects are yet to come.</p>
</list-item>
<list-item>
<p id="Par11">Coronavirus phylogeny shows an incredible diversity in antigenic variants, which leads to limited cross-protection against infection with different strains, even within a phylogenetic subcluster. Consequently, the risk of introducing novel coronaviruses into naive human and animal populations remains high.</p>
</list-item>
</list>
</p>
<sec>
<title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/nrmicro3143) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<abstract id="Abs2" abstract-type="web-summary">
<p id="Par12">The emergence of severe acute respiratory syndrome (SARS) coronavirus and, more recently, Middle East respiratory syndrome (MERS) coronavirus has highlighted the pathogenic and epidemic potential of this virus family. Here, Graham, Donaldson and Baric review key biological properties of coronaviruses and how to target them with potential therapeutics.</p>
<sec>
<title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/nrmicro3143) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<abstract id="Abs3">
<p id="Par13">Two novel coronaviruses have emerged in humans in the twenty-first century: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which cause acute respiratory distress syndrome (ARDS) and are associated with high mortality rates. There are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, the development of effective therapeutic and preventive strategies that can be readily applied to new emergent strains is a research priority. In this Review, we describe the emergence and identification of novel human coronaviruses over the past 10 years, discuss their key biological features, including tropism and receptor use, and summarize approaches for developing broadly effective vaccines.</p>
<sec>
<title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/nrmicro3143) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<kwd-group kwd-group-type="npg-subject">
<title>Subject terms</title>
<kwd>SARS virus</kwd>
<kwd>Pathogens</kwd>
<kwd>Viral infection</kwd>
<kwd>Viral epidemiology</kwd>
<kwd>Vaccines</kwd>
</kwd-group>
<custom-meta-group>
<custom-meta>
<meta-name>issue-copyright-statement</meta-name>
<meta-value>© Springer Nature Limited 2013</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>

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