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http://aac.asm.org/content/early/201...36-14.abstract
http://aac.asm.org/content/early/201...36-14.abstract
Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection
Julie Dyalla,
Christopher M. Colemanb,
Brit J. Harta,
Thiagarajan Venkataramanb,
Michael R. Holbrooka,
Jason Kindrachuka,
Reed F. Johnsonc,
Gene G. Olinger Jr.a,
Peter B. Jahrlinga,c,
Monique Laidlawd,
Lisa M. Johansend,
Calli M. Leare,
Pamela J. Glasse,
Lisa E. Hensleya and
Matthew B. Friemanb#
+ Author Affiliations
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USAa
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USAb
Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USAc
Zalicus Inc, Cambridge, Massachusetts, USAd
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USAe
ABSTRACT
Outbreaks of emerging infections present 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 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 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 Eastern 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 were included that had a well-defined cellular pathway as target. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to thirteen 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.
Julie Dyalla,
Christopher M. Colemanb,
Brit J. Harta,
Thiagarajan Venkataramanb,
Michael R. Holbrooka,
Jason Kindrachuka,
Reed F. Johnsonc,
Gene G. Olinger Jr.a,
Peter B. Jahrlinga,c,
Monique Laidlawd,
Lisa M. Johansend,
Calli M. Leare,
Pamela J. Glasse,
Lisa E. Hensleya and
Matthew B. Friemanb#
+ Author Affiliations
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USAa
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USAb
Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USAc
Zalicus Inc, Cambridge, Massachusetts, USAd
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USAe
ABSTRACT
Outbreaks of emerging infections present 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 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 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 Eastern 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 were included that had a well-defined cellular pathway as target. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to thirteen 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.
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