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Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus.
- Source :
- Journal of Infection; Dec2013, Vol. 67 Issue 6, p606-616, 11p
- Publication Year :
- 2013
-
Abstract
- Summary: 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<subscript>50</subscript> 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<subscript>50</subscript> of each drug by 1–3 times. Conclusions: Interferon-β1b with mycophenolic acid should be considered in treatment trials of MERS. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 01634453
- Volume :
- 67
- Issue :
- 6
- Database :
- Supplemental Index
- Journal :
- Journal of Infection
- Publication Type :
- Academic Journal
- Accession number :
- 91816203
- Full Text :
- https://doi.org/10.1016/j.jinf.2013.09.029