Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus
Identifieur interne : 002221 ( Main/Merge ); précédent : 002220; suivant : 002222Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus
Auteurs : Jasper F. W. Chan [République populaire de Chine] ; Kwok-Hung Chan [République populaire de Chine] ; Richard Y. T. Kao [République populaire de Chine] ; Kelvin K. W. To [République populaire de Chine] ; Bo-Jian Zheng [République populaire de Chine] ; Clara P. Y. Li [République populaire de Chine] ; Patrick T. W. Li [République populaire de Chine] ; JUN DAI [République populaire de Chine] ; Florence K. Y. Mok [République populaire de Chine] ; HONGLIN CHEN [République populaire de Chine] ; Frederick G. Hayden [États-Unis] ; Kwok-Yung Yuen [République populaire de Chine]Source :
- The Journal of infection [ 0163-4453 ] ; 2013.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
Objectives: Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged to cause fatal infections in patients in the Middle East and traveler-associated secondary cases in Europe and Africa. Person-to-person transmission is evident in outbreaks involving household and hospital contacts. Effective antivirals are urgently needed. Methods: We used small compound-based forward chemical genetics to screen a chemical library of 1280 known drugs against influenza A virus in Biosafety Level-2 laboratory. We then assessed the anti-MERS-CoV activities of the identified compounds and of interferons, nelfinavir, and lopinavir because of their reported anti-coronavirus activities in terms of cytopathic effect inhibition, viral yield reduction, and plaque reduction assays in Biosafety Level-3 laboratory. Results: Ten compounds were identified as primary hits in high-throughput screening. Only mycophenolic acid exhibited low EC50 and high selectivity index. Additionally, ribavirin and interferons also exhibited in-vitro anti-MERS-CoV activity. The serum concentrations achievable at therapeutic doses of mycophenolic acid and interferon-β1b were 60-300 and 3-4 times higher than the concentrations at which in-vitro anti-MERS-CoV activities were demonstrated, whereas that of ribavirin was ∼2 times lower. Combination of mycophenolic acid and interferon-β1b lowered the EC50 of each drug by 1-3 times. Conclusions: Interferon-β1b with mycophenolic acid should be considered in treatment trials of MERS.
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus</title>
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<author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
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</affiliation>
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<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
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<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
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</author>
<author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
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<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, The University of Hong Kong</s1>
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<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Research Centre of Infection and Immunology, The University of Hong Kong</s1>
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<wicri:noRegion>Hong Kong</wicri:noRegion>
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</author>
<author><name sortKey="Li, Clara P Y" sort="Li, Clara P Y" uniqKey="Li C" first="Clara P. Y." last="Li">Clara P. Y. Li</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
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</affiliation>
</author>
<author><name sortKey="Li, Patrick T W" sort="Li, Patrick T W" uniqKey="Li P" first="Patrick T. W." last="Li">Patrick T. W. Li</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
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<country>République populaire de Chine</country>
<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
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<author><name sortKey="Jun Dai" sort="Jun Dai" uniqKey="Jun Dai" last="Jun Dai">JUN DAI</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
<s3>CHN</s3>
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<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mok, Florence K Y" sort="Mok, Florence K Y" uniqKey="Mok F" first="Florence K. Y." last="Mok">Florence K. Y. Mok</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
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<wicri:noRegion>Hong Kong</wicri:noRegion>
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</author>
<author><name sortKey="Honglin Chen" sort="Honglin Chen" uniqKey="Honglin Chen" last="Honglin Chen">HONGLIN CHEN</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
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<country>République populaire de Chine</country>
<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, The University of Hong Kong</s1>
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<country>République populaire de Chine</country>
<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Research Centre of Infection and Immunology, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
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</affiliation>
</author>
<author><name sortKey="Hayden, Frederick G" sort="Hayden, Frederick G" uniqKey="Hayden F" first="Frederick G." last="Hayden">Frederick G. Hayden</name>
<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine</s1>
<s2>Charlottesville, VA</s2>
<s3>USA</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
<s3>CHN</s3>
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<country>République populaire de Chine</country>
<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
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<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>12 aut.</sZ>
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<country>République populaire de Chine</country>
<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Research Centre of Infection and Immunology, The University of Hong Kong</s1>
<s2>Hong Kong</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
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<country>République populaire de Chine</country>
<wicri:noRegion>Hong Kong</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">The Journal of infection</title>
<title level="j" type="abbreviated">J. infect.</title>
<idno type="ISSN">0163-4453</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">The Journal of infection</title>
<title level="j" type="abbreviated">J. infect.</title>
<idno type="ISSN">0163-4453</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral</term>
<term>Coronavirus</term>
<term>Infection</term>
<term>Middle East respiratory syndrome</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Infection</term>
<term>Antiviral</term>
<term>Coronavirus</term>
<term>Syndrome respiratoire du Moyen-Orient</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Objectives: Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged to cause fatal infections in patients in the Middle East and traveler-associated secondary cases in Europe and Africa. Person-to-person transmission is evident in outbreaks involving household and hospital contacts. Effective antivirals are urgently needed. Methods: We used small compound-based forward chemical genetics to screen a chemical library of 1280 known drugs against influenza A virus in Biosafety Level-2 laboratory. We then assessed the anti-MERS-CoV activities of the identified compounds and of interferons, nelfinavir, and lopinavir because of their reported anti-coronavirus activities in terms of cytopathic effect inhibition, viral yield reduction, and plaque reduction assays in Biosafety Level-3 laboratory. Results: Ten compounds were identified as primary hits in high-throughput screening. Only mycophenolic acid exhibited low EC<sub>50</sub>
and high selectivity index. Additionally, ribavirin and interferons also exhibited in-vitro anti-MERS-CoV activity. The serum concentrations achievable at therapeutic doses of mycophenolic acid and interferon-β1b were 60-300 and 3-4 times higher than the concentrations at which in-vitro anti-MERS-CoV activities were demonstrated, whereas that of ribavirin was ∼2 times lower. Combination of mycophenolic acid and interferon-β1b lowered the EC<sub>50</sub>
of each drug by 1-3 times. Conclusions: Interferon-β1b with mycophenolic acid should be considered in treatment trials of MERS.</div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Virginie</li>
</region>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Chan, Jasper F W" sort="Chan, Jasper F W" uniqKey="Chan J" first="Jasper F. W." last="Chan">Jasper F. W. Chan</name>
</noRegion>
<name sortKey="Chan, Jasper F W" sort="Chan, Jasper F W" uniqKey="Chan J" first="Jasper F. W." last="Chan">Jasper F. W. Chan</name>
<name sortKey="Chan, Jasper F W" sort="Chan, Jasper F W" uniqKey="Chan J" first="Jasper F. W." last="Chan">Jasper F. W. Chan</name>
<name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
<name sortKey="Honglin Chen" sort="Honglin Chen" uniqKey="Honglin Chen" last="Honglin Chen">HONGLIN CHEN</name>
<name sortKey="Honglin Chen" sort="Honglin Chen" uniqKey="Honglin Chen" last="Honglin Chen">HONGLIN CHEN</name>
<name sortKey="Honglin Chen" sort="Honglin Chen" uniqKey="Honglin Chen" last="Honglin Chen">HONGLIN CHEN</name>
<name sortKey="Jun Dai" sort="Jun Dai" uniqKey="Jun Dai" last="Jun Dai">JUN DAI</name>
<name sortKey="Kao, Richard Y T" sort="Kao, Richard Y T" uniqKey="Kao R" first="Richard Y. T." last="Kao">Richard Y. T. Kao</name>
<name sortKey="Kao, Richard Y T" sort="Kao, Richard Y T" uniqKey="Kao R" first="Richard Y. T." last="Kao">Richard Y. T. Kao</name>
<name sortKey="Kao, Richard Y T" sort="Kao, Richard Y T" uniqKey="Kao R" first="Richard Y. T." last="Kao">Richard Y. T. Kao</name>
<name sortKey="Li, Clara P Y" sort="Li, Clara P Y" uniqKey="Li C" first="Clara P. Y." last="Li">Clara P. Y. Li</name>
<name sortKey="Li, Patrick T W" sort="Li, Patrick T W" uniqKey="Li P" first="Patrick T. W." last="Li">Patrick T. W. Li</name>
<name sortKey="Mok, Florence K Y" sort="Mok, Florence K Y" uniqKey="Mok F" first="Florence K. Y." last="Mok">Florence K. Y. Mok</name>
<name sortKey="To, Kelvin K W" sort="To, Kelvin K W" uniqKey="To K" first="Kelvin K. W." last="To">Kelvin K. W. To</name>
<name sortKey="To, Kelvin K W" sort="To, Kelvin K W" uniqKey="To K" first="Kelvin K. W." last="To">Kelvin K. W. To</name>
<name sortKey="To, Kelvin K W" sort="To, Kelvin K W" uniqKey="To K" first="Kelvin K. W." last="To">Kelvin K. W. To</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
<name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
<name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
</country>
<country name="États-Unis"><region name="Virginie"><name sortKey="Hayden, Frederick G" sort="Hayden, Frederick G" uniqKey="Hayden F" first="Frederick G." last="Hayden">Frederick G. Hayden</name>
</region>
</country>
</tree>
</affiliations>
</record>
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