Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection.
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.
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Julie
J
Dyall
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Christopher M
CM
Coleman
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Brit J
BJ
Hart
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Thiagarajan
T
Venkataraman
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Michael R
MR
Holbrook
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Jason
J
Kindrachuk
Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Reed F
RF
Johnson
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Gene G
GG
Olinger
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Peter B
PB
Jahrling
Zalicus Inc., Cambridge, Massachusetts, USA.
Monique
M
Laidlaw
Zalicus Inc., Cambridge, Massachusetts, USA.
Lisa M
LM
Johansen
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
Calli M
CM
Lear-Rooney
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
Pamela J
PJ
Glass
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Lisa E
LE
Hensley
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA MFrieman@som.umaryland.edu.
Matthew B
MB
Frieman
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D017277:Drug Approval; D058492:Drug Repositioning; D004965:Estrogen Antagonists / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D006801:Humans; D020128:Inhibitory Concentration 50; D065207:Middle East Respiratory Syndrome Coronavirus / Q000187:drug effects* / Q000502:physiology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000502:physiology; D054852:Small Molecule Libraries / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D014150:Antipsychotic Agents; D000998:Antiviral Agents; D004965:Estrogen Antagonists; D054852:Small Molecule Libraries