title: Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.
abstract: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. Therapeutic interventions have not been evaluated in vivo; thus, patient management relies exclusively on supportive care, which, given the high case-fatality rate, is not highly effective. The rhesus macaque is the only known model organism for MERS-CoV infection, developing an acute localized to widespread pneumonia with transient clinical disease that recapitulates mild to moderate human MERS-CoV cases. The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro; therefore, we initiated this treatment 8 h after inoculation of rhesus macaques. In contrast to untreated, infected macaques, treated animals did not develop breathing abnormalities and showed no or very mild radiographic evidence of pneumonia. Moreover, treated animals showed lower levels of systemic (serum) and local (lung) proinflammatory markers, in addition to fewer viral genome copies, distinct gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic for other infections, IFN-α2b and ribavirin should be considered for the management of MERS-CoV cases.
authors.affiliation: Disease Modeling and Transmission Unit, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, USA.
authors.forename: Darryl
authors.initials: D
authors.lastname: Falzarano
authors.forename: Emmie
authors.initials: E
authors.lastname: de Wit
authors.forename: Angela L
authors.initials: AL
authors.lastname: Rasmussen
authors.forename: Friederike
authors.initials: F
authors.lastname: Feldmann
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okumura
authors.forename: Dana P
authors.initials: DP
authors.lastname: Scott
authors.forename: Doug
authors.initials: D
authors.lastname: Brining
authors.forename: Trenton
authors.initials: T
authors.lastname: Bushmaker
authors.forename: Cynthia
authors.initials: C
authors.lastname: Martellaro
authors.forename: Laura
authors.initials: L
authors.lastname: Baseler
authors.forename: Arndt G
authors.initials: AG
authors.lastname: Benecke
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Munster
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D017934:Coronavirus / Q000502:physiology; D018352:Coronavirus Infections / Q000188:drug therapy*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008253:Macaca mulatta; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin