title: Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays.
abstract: The Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel emerging threat to public health worldwide. Several treatments for infected individuals have been suggested including IFN, ribavirin and passive immunotherapy with convalescent plasma. Administration of IFN-α2b and ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when administered within 8 h post-challenge. However, detailed and systematic evidence on the activity of other clinically available drugs is limited. Here we compared the susceptibility of MERS-CoV with different IFN products (IFN-α2b, IFN-γ, IFN-universal, IFN-α2a and IFN-β), as well as with two antivirals, ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in vitro. Of all the IFNs tested, IFN-β showed the strongst inhibition of MERS-CoV in vitro, with an IC₅₀ of 1.37 U ml(-1), 41 times lower than the previously reported IC₅₀ (56.08 U ml(-1)) of IFN-α2b. IFN-β inhibition was confirmed in the virus yield reduction assay, with an IC90 of 38.8 U ml(-1). Ribavirin did not inhibit viral replication in vitro at a dose that would be applicable to current treatment protocols in humans. In contrast, MPA showed strong inhibition, with an IC₅₀ of 2.87 µM. This drug has not been previously tested against MERS-CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-β, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV.
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
authors: Brit J
authors: BJ
authors: Hart
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
authors: Julie
authors: J
authors: Dyall
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
authors: Elena
authors: E
authors: Postnikova
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
authors: Huanying
authors: H
authors: Zhou
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
authors: Jason
authors: J
authors: Kindrachuk
authors: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.
authors: Reed F
authors: RF
authors: Johnson
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
authors: Gene G
authors: GG
authors: Olinger
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Matthew B
authors: MB
authors: Frieman
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
authors: Michael R
authors: MR
authors: Holbrook
authors: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.|Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
authors: Peter B
authors: PB
authors: Jahrling
authors: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederik, MD, USA.
authors: Lisa
authors: L
authors: Hensley
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003332:Coronaviridae / Q000187:drug effects* / Q000502:physiology; D003333:Coronaviridae Infections / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D009173:Mycophenolic Acid / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D007372:Interferons; D009173:Mycophenolic Acid