Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus
| Autor: | Kwok-Yung Yuen, Honglin Chen, Clara P. Y. Li, Bo-Jian Zheng, Patrick T.W. Li, Kwok-Hung Chan, Frederick G. Hayden, Florence K.Y. Mok, Kelvin K. W. To, Jun Dai, Richard Y.T. Kao, Jasper Fuk-Woo Chan |
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| Rok vydání: | 2013 |
| Předmět: |
Microbiology (medical)
Middle East respiratory syndrome coronavirus Viral Plaque Assay Pharmacology Biology medicine.disease_cause Antiviral Agents Communicable Diseases Emerging Article Mycophenolic acid Disease Outbreaks Middle East Biosafety chemistry.chemical_compound Chlorocebus aethiops Drug Discovery Ribavirin medicine Influenza A virus Animals Humans Antiviral Vero Cells Coronavirus virus diseases Lopinavir Mycophenolic Acid Viral Load Virology High-Throughput Screening Assays Infectious Diseases Nelfinavir chemistry Interferon Interferons Coronavirus Infections medicine.drug |
| Zdroj: | The Journal of Infection |
| ISSN: | 0163-4453 |
| DOI: | 10.1016/j.jinf.2013.09.029 |
| Popis: | 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 50 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 50 of each drug by 1–3 times. Conclusions Interferon-β1b with mycophenolic acid should be considered in treatment trials of MERS. |
| Databáze: | OpenAIRE |
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