Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection

By J. Dyall, C. Coleman, Brit J. Hart, Thiagarajan Venkataraman, M. Holbrook, J. Kindrachuk, Reed F. Johnson, G. Olinger, P. Jahrling, M. Laidlaw and 5 more. Antimicrobial Agents and Chemotherapy, 2014

629 citations recorded by the source corpus.

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.

Subfields: Computational Theory and Mathematics, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/746eb4349e92ef23d8fe3eab8f5dbb368afc80c5

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In Infectious Diseases

1. J. Chan
2. Guangdi Li
3. Kwok-Yung Yuen
4. E. Snijder
5. E. De Clercq
6. Jun Zheng

In Molecular Biology

1. Xuhui Huang
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Citations in the corpus

• Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro (2020, background): “Emetine was also identified to inhibit hCoV-OC43, hCoV-NL43, SARS-CoV, MERS-CoV, and MHV-A59 in vitro with EC50 reported at low micromolar range (Dyall et al., 2014; Shen et al., 2019).”
• Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset (2015, methodology): “In order to find immediately available treatment for MERS before these novel agents and convalescent-phase plasma therapy become available, we and others have applied highthroughput screening to identify existing drugs that may be repurposed to treat patients with MERS [15] [16] [17] .”
• Therapeutic options for the 2019 novel coronavirus (2019-nCoV) (2020, background): “• Randomized trial for SARS (NCT00578825) [2-8] 2019-nCoV RdRp Penciclovir Inhibits RdRp Approved for HSV [2] 2019-nCoV, MERS-CoV, SARS-CoV RdRp Remdesivir (GS-5734) Terminates the non-obligate chain • Phase 3 for 2019-nCoV (NCT04252664, NCT04257656) • Phase 1 for Ebola (NCT03719586) [1,2, 9-11] Bro”
• Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture (2014, background): “(85), CQ and CPZ were identified as inhibitors of the MERS-CoV as well.”
• Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods (2020, neutral): “PII: S2211-3835(20)30299-9 DOI: https://doi.”