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J Infect. 2013 Dec;67(6):606-16. doi: 10.1016/j.jinf.2013.09.029. Epub 2013 Oct 3.

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

Author information

1
State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China; Department of Microbiology, The University of Hong Kong, Hong Kong, China; Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.

Abstract

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-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.

KEYWORDS:

Antiviral; Coronavirus; Interferon; Middle East; Mycophenolic acid; Ribavirin

PMID:
24096239
DOI:
10.1016/j.jinf.2013.09.029
[Indexed for MEDLINE]

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