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Article: Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus.

TitleBroad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus.
Authors
Issue Date2013
Citation
Journal of Infection, 2013, v. 67 n. 6, p. 606-16. How to Cite?
AbstractObjectives 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.
Persistent Identifierhttp://hdl.handle.net/10722/199181
ISSN
2015 Impact Factor: 4.382
2015 SCImago Journal Rankings: 2.070
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, JFWen_US
dc.contributor.authorChan, KHen_US
dc.contributor.authorKao, RYTen_US
dc.contributor.authorTo, KKWen_US
dc.contributor.authorZheng, Ben_US
dc.contributor.authorLi, PYen_US
dc.contributor.authorLi, TWen_US
dc.contributor.authorDai, Jen_US
dc.contributor.authorMok, KYen_US
dc.contributor.authorChen, Hen_US
dc.contributor.authorHayden, FGen_US
dc.contributor.authorYuen, KYen_US
dc.date.accessioned2014-07-22T01:06:16Z-
dc.date.available2014-07-22T01:06:16Z-
dc.date.issued2013en_US
dc.identifier.citationJournal of Infection, 2013, v. 67 n. 6, p. 606-16.en_US
dc.identifier.issn0163-4453-
dc.identifier.urihttp://hdl.handle.net/10722/199181-
dc.description.abstractObjectives 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.en_US
dc.languageengen_US
dc.relation.ispartofJournal of Infectionen_US
dc.titleBroad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus.en_US
dc.typeArticleen_US
dc.identifier.emailChan, JFW: jfwchan@hku.hken_US
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hken_US
dc.identifier.emailKao, RYT: rytkao@hkucc.hku.hken_US
dc.identifier.emailTo, KKW: kelvinto@hkucc.hku.hken_US
dc.identifier.emailZheng, B: bzheng@hkucc.hku.hken_US
dc.identifier.emailLi, PY: coloryan@hku.hken_US
dc.identifier.emailLi, TW: twli2000@hku.hken_US
dc.identifier.emailDai, J: ddaijun@hku.hken_US
dc.identifier.emailMok, KY: kymokaa@hku.hken_US
dc.identifier.emailChen, H: hlchen@hku.hken_US
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hken_US
dc.identifier.authorityChan, JFW=rp01736en_US
dc.identifier.authorityKao, RYT=rp00481en_US
dc.identifier.authorityTo, KKW=rp01384en_US
dc.identifier.authorityZheng, B=rp00353en_US
dc.identifier.authorityChen, H=rp00383en_US
dc.identifier.authorityYuen, KY=rp00366en_US
dc.identifier.doi10.1016/j.jinf.2013.09.029en_US
dc.identifier.pmid24096239-
dc.identifier.scopuseid_2-s2.0-84887019388-
dc.identifier.hkuros230807en_US
dc.identifier.volume67en_US
dc.identifier.issue6en_US
dc.identifier.spage606en_US
dc.identifier.epage16.en_US
dc.identifier.isiWOS:000326588400012-

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