Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus
Identifieur interne : 000060 ( PascalFrancis/Checkpoint ); précédent : 000059; suivant : 000061Broad-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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Chan</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><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><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><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><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><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><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><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></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><s3>CHN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></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><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></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><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><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><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></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><s3>CHN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></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><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">14-0004676</idno><date when="2013">2013</date><idno type="stanalyst">PASCAL 14-0004676 INIST</idno><idno type="RBID">Pascal:14-0004676</idno><idno type="wicri:Area/PascalFrancis/Corpus">000037</idno><idno type="wicri:Area/PascalFrancis/Curation">000057</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000060</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000060</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus</title><author><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><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><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><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><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><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><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><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><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></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><s3>CHN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></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><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></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><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><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><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></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><s3>CHN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Hong Kong</wicri:noRegion></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><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><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><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0163-4453</s0></fA01><fA02 i1="01"><s0>JINFD2</s0></fA02><fA03 i2="1"><s0>J. infect.</s0></fA03><fA05><s2>67</s2></fA05><fA06><s2>6</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus</s1></fA08><fA11 i1="01" i2="1"><s1>CHAN (Jasper F. W.)</s1></fA11><fA11 i1="02" i2="1"><s1>CHAN (Kwok-Hung)</s1></fA11><fA11 i1="03" i2="1"><s1>KAO (Richard Y. T.)</s1></fA11><fA11 i1="04" i2="1"><s1>TO (Kelvin K. W.)</s1></fA11><fA11 i1="05" i2="1"><s1>ZHENG (Bo-Jian)</s1></fA11><fA11 i1="06" i2="1"><s1>LI (Clara P. Y.)</s1></fA11><fA11 i1="07" i2="1"><s1>LI (Patrick T. W.)</s1></fA11><fA11 i1="08" i2="1"><s1>JUN DAI</s1></fA11><fA11 i1="09" i2="1"><s1>MOK (Florence K. Y.)</s1></fA11><fA11 i1="10" i2="1"><s1>HONGLIN CHEN</s1></fA11><fA11 i1="11" i2="1"><s1>HAYDEN (Frederick G.)</s1></fA11><fA11 i1="12" i2="1"><s1>YUEN (Kwok-Yung)</s1></fA11><fA14 i1="01"><s1>State Key Laboratory of Emerging Infectious Diseases, 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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></fA14><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><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></fA14><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><sZ>10 aut.</sZ><sZ>12 aut.</sZ></fA14><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></fA14><fA20><s1>606-616</s1></fA20><fA21><s1>2013</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>18250</s2><s5>354000507410410120</s5></fA43><fA44><s0>0000</s0><s1>© 2014 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>73 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>14-0004676</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>The Journal of infection</s0></fA64><fA66 i1="01"><s0>NLD</s0></fA66><fC01 i1="01" l="ENG"><s0>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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B01</s0></fC02><fC02 i1="02" i2="X"><s0>002B02S05</s0></fC02><fC02 i1="03" i2="X"><s0>002B05C02C</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Infection</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Infection</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Infección</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Antiviral</s0><s5>04</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Antiviral</s0><s5>04</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Antiviral</s0><s5>04</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Coronavirus</s0><s2>NW</s2><s5>10</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Coronavirus</s0><s2>NW</s2><s5>10</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Coronavirus</s0><s2>NW</s2><s5>10</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Syndrome respiratoire du Moyen-Orient</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Middle East respiratory syndrome</s0><s4>CD</s4><s5>96</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Pathologie de l'appareil respiratoire</s0><s5>37</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Respiratory disease</s0><s5>37</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0><s5>37</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Virose</s0><s5>38</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Viral disease</s0><s5>38</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Virosis</s0><s5>38</s5></fC07><fN21><s1>006</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><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>Pour manipuler ce document sous Unix (Dilib)
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