Effect of interferon alpha and cyclosporine treatment separately and in combination on Middle East Respiratory Syndrome Coronavirus (MERS-CoV) replication in a human in-vitro and ex-vivo culture model

Antiviral Res. 2018 Jul:155:89-96. doi: 10.1016/j.antiviral.2018.05.007. Epub 2018 May 17.

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has emerged as a coronavirus infection of humans in the past 5 years. Though confined to certain geographical regions of the world, infection has been associated with a case fatality rate of 35%, and this mortality may be higher in ventilated patients. As there are few readily available animal models that accurately mimic human disease, it has been a challenge to ethically determine what optimum treatment strategies can be used for this disease. We used in-vitro and human ex-vivo explant cultures to investigate the effect of two immunomodulatory agents, interferon alpha and cyclosporine, singly and in combination, on MERS-CoV replication. In both culture systems the combined treatment was more effective than either agent used alone in reducing MERS-CoV replication. PCR SuperArray analysis showed that the reduction of virus replication was associated with a greater induction of interferon stimulated genes. As these therapeutic agents are already licensed for clinical use, it may be relevant to investigate their use for therapy of human MERS-CoV infection.

Keywords: Cyclosporine; Ex vivo explants; Middle East Respiratory Syndrome Coronavirus (MERS-CoV); Type I interferon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Bronchi / physiology
  • Bronchi / virology
  • Cell Culture Techniques
  • Cyclosporine / pharmacology*
  • DNA Replication
  • Humans
  • Interferon-alpha / pharmacology*
  • Lung / physiology
  • Lung / virology
  • Middle East Respiratory Syndrome Coronavirus / drug effects*
  • Respiratory System / virology
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Cyclosporine