期刊
JOURNAL OF INFECTION
卷 67, 期 6, 页码 606-616出版社
W B SAUNDERS CO LTD
DOI: 10.1016/j.jinf.2013.09.029
关键词
Coronavirus; Middle East; Mycophenolic acid; Interferon; Ribavirin; Antiviral
资金
- Hui Hoy and Chow Sin Lan Charity Fund Limited
- National Science and Technology Major Project of China [2012ZX10004-213-002]
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-b1b 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 wasw2 times lower. Combination of mycophenolic acid and interferon-b1b lowered the EC50 of each drug by 1-3 times. Conclusions: Interferon-b1b with mycophenolic acid should be considered in treatment trials of MERS. (C) 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
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