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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
KeywordsAntiviral
Coronavirus
Interferon
Middle East
Mycophenolic acid
Ribavirin
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
2020 Impact Factor: 6.072
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.subjectAntiviral-
dc.subjectCoronavirus-
dc.subjectInterferon-
dc.subjectMiddle East-
dc.subjectMycophenolic acid-
dc.subjectRibavirin-
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-
dc.identifier.issnl0163-4453-

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