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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Chlorocebus aethiops
  • Communicable Diseases, Emerging / drug therapy
  • Communicable Diseases, Emerging / virology*
  • Coronavirus / drug effects*
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / virology*
  • Disease Outbreaks
  • Drug Discovery / methods
  • High-Throughput Screening Assays / methods
  • Humans
  • Interferons / pharmacology
  • Mycophenolic Acid / pharmacology
  • Ribavirin / pharmacology
  • Vero Cells
  • Viral Load / drug effects
  • Viral Plaque Assay


  • Antiviral Agents
  • Ribavirin
  • Interferons
  • Mycophenolic Acid