Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection

Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93. doi: 10.1128/AAC.03036-14. Epub 2014 May 19.

Abstract

Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies.

Publication types

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

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology
  • Antiviral Agents / pharmacology*
  • Chlorocebus aethiops
  • Drug Approval
  • Drug Repositioning*
  • Estrogen Antagonists / pharmacology
  • High-Throughput Screening Assays
  • Humans
  • Inhibitory Concentration 50
  • Middle East Respiratory Syndrome Coronavirus / drug effects*
  • Middle East Respiratory Syndrome Coronavirus / physiology
  • SARS Virus / drug effects*
  • SARS Virus / physiology
  • Small Molecule Libraries / pharmacology*
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antipsychotic Agents
  • Antiviral Agents
  • Estrogen Antagonists
  • Small Molecule Libraries