Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus
Identifieur interne : 000037 ( PascalFrancis/Corpus ); précédent : 000036; suivant : 000038Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus
Auteurs : Jasper F. W. Chan ; Kwok-Hung Chan ; Richard Y. T. Kao ; Kelvin K. W. To ; Bo-Jian Zheng ; Clara P. Y. Li ; Patrick T. W. Li ; JUN DAI ; Florence K. Y. Mok ; HONGLIN CHEN ; Frederick G. Hayden ; Kwok-Yung YuenSource :
- 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.
Notice en format standard (ISO 2709)
Pour connaître la documentation sur le format Inist Standard.
| pA |
|
|---|
Format Inist (serveur)
| NO : | PASCAL 14-0004676 INIST |
|---|---|
| ET : | Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus |
| AU : | CHAN (Jasper F. W.); CHAN (Kwok-Hung); KAO (Richard Y. T.); TO (Kelvin K. W.); ZHENG (Bo-Jian); LI (Clara P. Y.); LI (Patrick T. W.); JUN DAI; MOK (Florence K. Y.); HONGLIN CHEN; HAYDEN (Frederick G.); YUEN (Kwok-Yung) |
| AF : | State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong/Hong Kong/Chine (1 aut., 3 aut., 4 aut., 5 aut., 10 aut., 12 aut.); Department of Microbiology, The University of Hong Kong/Hong Kong/Chine (1 aut., 2 aut., 3 aut., 4 aut., 5 aut., 6 aut., 7 aut., 8 aut., 9 aut., 10 aut., 12 aut.); Research Centre of Infection and Immunology, The University of Hong Kong/Hong Kong/Chine (1 aut., 3 aut., 4 aut., 5 aut., 10 aut., 12 aut.); Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine/Charlottesville, VA/Etats-Unis (11 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | The Journal of infection; ISSN 0163-4453; Coden JINFD2; Pays-Bas; Da. 2013; Vol. 67; No. 6; Pp. 606-616; Bibl. 73 ref. |
| LA : | Anglais |
| EA : | 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. |
| CC : | 002B01; 002B02S05; 002B05C02C |
| FD : | Infection; Antiviral; Coronavirus; Syndrome respiratoire du Moyen-Orient |
| FG : | Coronaviridae; Nidovirales; Virus; Pathologie de l'appareil respiratoire; Virose |
| ED : | Infection; Antiviral; Coronavirus; Middle East respiratory syndrome |
| EG : | Coronaviridae; Nidovirales; Virus; Respiratory disease; Viral disease |
| SD : | Infección; Antiviral; Coronavirus |
| LO : | INIST-18250.354000507410410120 |
| ID : | 14-0004676 |
Links to Exploration step
Pascal:14-0004676Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></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><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></affiliation></author><author><name sortKey="Jun Dai" sort="Jun Dai" uniqKey="Jun Dai" last="Jun Dai">JUN DAI</name><affiliation><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></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><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></affiliation></author><author><name sortKey="Honglin Chen" sort="Honglin Chen" uniqKey="Honglin Chen" last="Honglin Chen">HONGLIN CHEN</name><affiliation><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></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><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></affiliation></author><author><name sortKey="Jun Dai" sort="Jun Dai" uniqKey="Jun Dai" last="Jun Dai">JUN DAI</name><affiliation><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></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><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></affiliation></author><author><name sortKey="Honglin Chen" sort="Honglin Chen" uniqKey="Honglin Chen" last="Honglin Chen">HONGLIN CHEN</name><affiliation><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><server><NO>PASCAL 14-0004676 INIST</NO><ET>Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus</ET><AU>CHAN (Jasper F. W.); CHAN (Kwok-Hung); KAO (Richard Y. T.); TO (Kelvin K. W.); ZHENG (Bo-Jian); LI (Clara P. Y.); LI (Patrick T. W.); JUN DAI; MOK (Florence K. Y.); HONGLIN CHEN; HAYDEN (Frederick G.); YUEN (Kwok-Yung)</AU><AF>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong/Hong Kong/Chine (1 aut., 3 aut., 4 aut., 5 aut., 10 aut., 12 aut.); Department of Microbiology, The University of Hong Kong/Hong Kong/Chine (1 aut., 2 aut., 3 aut., 4 aut., 5 aut., 6 aut., 7 aut., 8 aut., 9 aut., 10 aut., 12 aut.); Research Centre of Infection and Immunology, The University of Hong Kong/Hong Kong/Chine (1 aut., 3 aut., 4 aut., 5 aut., 10 aut., 12 aut.); Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine/Charlottesville, VA/Etats-Unis (11 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>The Journal of infection; ISSN 0163-4453; Coden JINFD2; Pays-Bas; Da. 2013; Vol. 67; No. 6; Pp. 606-616; Bibl. 73 ref.</SO><LA>Anglais</LA><EA>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.</EA><CC>002B01; 002B02S05; 002B05C02C</CC><FD>Infection; Antiviral; Coronavirus; Syndrome respiratoire du Moyen-Orient</FD><FG>Coronaviridae; Nidovirales; Virus; Pathologie de l'appareil respiratoire; Virose</FG><ED>Infection; Antiviral; Coronavirus; Middle East respiratory syndrome</ED><EG>Coronaviridae; Nidovirales; Virus; Respiratory disease; Viral disease</EG><SD>Infección; Antiviral; Coronavirus</SD><LO>INIST-18250.354000507410410120</LO><ID>14-0004676</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/PascalFrancis/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000037 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PascalFrancis/Corpus/biblio.hfd -nk 000037 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= PascalFrancis
|étape= Corpus
|type= RBID
|clé= Pascal:14-0004676
|texte= Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus
}}
| This area was generated with Dilib version V0.6.33. |  |