Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus
Identifieur interne : 002196 ( Main/Exploration ); précédent : 002195; suivant : 002197Broad-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
- KwdFr :
- Acide mycophénolique (pharmacologie), Animaux, Antiviraux (pharmacologie), Cellules Vero, Charge virale (), Coronavirus (), Découverte de médicament (), Flambées de maladies, Humains, Infections à coronavirus (traitement médicamenteux), Infections à coronavirus (virologie), Interférons (pharmacologie), Maladies transmissibles émergentes (traitement médicamenteux), Maladies transmissibles émergentes (virologie), Méthode des plages virales, Ribavirine (pharmacologie), Tests de criblage à haut débit ().
- MESH :
- pharmacologie : Acide mycophénolique, Antiviraux, Interférons, Ribavirine.
- traitement médicamenteux : Infections à coronavirus, Maladies transmissibles émergentes.
- virologie : Infections à coronavirus, Maladies transmissibles émergentes.
- Pascal (Inist)
English descriptors
- KwdEn :
- Animals, Antiviral, Antiviral Agents (pharmacology), Chlorocebus aethiops, Communicable Diseases, Emerging (drug therapy), Communicable Diseases, Emerging (virology), Coronavirus, Coronavirus (drug effects), Coronavirus Infections (drug therapy), Coronavirus Infections (virology), Disease Outbreaks, Drug Discovery (methods), High-Throughput Screening Assays (methods), Humans, Infection, Interferons (pharmacology), Middle East respiratory syndrome, Mycophenolic Acid (pharmacology), Ribavirin (pharmacology), Vero Cells, Viral Load (drug effects), Viral Plaque Assay.
- MESH :
- chemical , pharmacology : Antiviral Agents, Interferons, Mycophenolic Acid, Ribavirin.
- drug effects : Coronavirus, Viral Load.
- drug therapy : Communicable Diseases, Emerging, Coronavirus Infections.
- methods : Drug Discovery, High-Throughput Screening Assays.
- virology : Communicable Diseases, Emerging, Coronavirus Infections.
- Animals, Chlorocebus aethiops, Disease Outbreaks, Humans, Vero Cells, Viral Plaque Assay.
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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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><idno type="wicri:doubleKey">0163-4453:2013:Chan J:broad:spectrum:antivirals</idno><idno type="wicri:Area/Main/Merge">002221</idno><idno type="wicri:source">PMC</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112612</idno><idno type="RBID">PMC:7112612</idno><idno type="wicri:Area/Pmc/Corpus">000E64</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E64</idno><idno type="wicri:Area/Pmc/Curation">000E64</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000E64</idno><idno type="wicri:Area/Pmc/Checkpoint">001257</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001257</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:24096239</idno><idno type="wicri:Area/PubMed/Corpus">001B65</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001B65</idno><idno type="wicri:Area/PubMed/Curation">001B65</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001B65</idno><idno type="wicri:Area/PubMed/Checkpoint">001B95</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001B95</idno><idno type="wicri:Area/Ncbi/Merge">000B74</idno><idno type="wicri:Area/Ncbi/Curation">000B74</idno><idno type="wicri:Area/Ncbi/Checkpoint">000B74</idno><idno type="wicri:doubleKey">0163-4453:2013:Chan J:broad:spectrum:antivirals</idno><idno type="wicri:Area/Main/Merge">002069</idno><idno type="wicri:Area/Main/Curation">002196</idno><idno type="wicri:Area/Main/Exploration">002196</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>Animals</term><term>Antiviral</term><term>Antiviral Agents (pharmacology)</term><term>Chlorocebus aethiops</term><term>Communicable Diseases, Emerging (drug therapy)</term><term>Communicable Diseases, Emerging (virology)</term><term>Coronavirus</term><term>Coronavirus (drug effects)</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (virology)</term><term>Disease Outbreaks</term><term>Drug Discovery (methods)</term><term>High-Throughput Screening Assays (methods)</term><term>Humans</term><term>Infection</term><term>Interferons (pharmacology)</term><term>Middle East respiratory syndrome</term><term>Mycophenolic Acid (pharmacology)</term><term>Ribavirin (pharmacology)</term><term>Vero Cells</term><term>Viral Load (drug effects)</term><term>Viral Plaque Assay</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acide mycophénolique (pharmacologie)</term><term>Animaux</term><term>Antiviraux (pharmacologie)</term><term>Cellules Vero</term><term>Charge virale ()</term><term>Coronavirus ()</term><term>Découverte de médicament ()</term><term>Flambées de maladies</term><term>Humains</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Infections à coronavirus (virologie)</term><term>Interférons (pharmacologie)</term><term>Maladies transmissibles émergentes (traitement médicamenteux)</term><term>Maladies transmissibles émergentes (virologie)</term><term>Méthode des plages virales</term><term>Ribavirine (pharmacologie)</term><term>Tests de criblage à haut débit ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Interferons</term><term>Mycophenolic Acid</term><term>Ribavirin</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Coronavirus</term><term>Viral Load</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Communicable Diseases, Emerging</term><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Drug Discovery</term><term>High-Throughput Screening Assays</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acide mycophénolique</term><term>Antiviraux</term><term>Interférons</term><term>Ribavirine</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term><term>Maladies transmissibles émergentes</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Maladies transmissibles émergentes</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Communicable Diseases, Emerging</term><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Disease Outbreaks</term><term>Humans</term><term>Vero Cells</term><term>Viral Plaque Assay</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Charge virale</term><term>Coronavirus</term><term>Découverte de médicament</term><term>Flambées de maladies</term><term>Humains</term><term>Infection</term><term>Antiviral</term><term>Coronavirus</term><term>Méthode des plages virales</term><term>Syndrome respiratoire du Moyen-Orient</term><term>Tests de criblage à haut débit</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>Pour manipuler ce document sous Unix (Dilib)
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