Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.
Identifieur interne : 001B94 ( PubMed/Corpus ); précédent : 001B93; suivant : 001B95Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.
Auteurs : Darryl Falzarano ; Emmie De Wit ; Angela L. Rasmussen ; Friederike Feldmann ; Atsushi Okumura ; Dana P. Scott ; Doug Brining ; Trenton Bushmaker ; Cynthia Martellaro ; Laura Baseler ; Arndt G. Benecke ; Michael G. Katze ; Vincent J. Munster ; Heinz FeldmannSource :
- Nature medicine [ 1546-170X ] ; 2013.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (therapeutic use), Coronavirus (physiology), Coronavirus Infections (drug therapy), Interferon alpha-2, Interferon-alpha (therapeutic use), Macaca mulatta, Real-Time Polymerase Chain Reaction, Recombinant Proteins (therapeutic use), Ribavirin (therapeutic use), Virus Replication.
- MESH :
- chemical , therapeutic use : Antiviral Agents, Interferon-alpha, Recombinant Proteins, Ribavirin.
- drug therapy : Coronavirus Infections.
- physiology : Coronavirus.
- Animals, Interferon alpha-2, Macaca mulatta, Real-Time Polymerase Chain Reaction, Virus Replication.
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.
DOI: 10.1038/nm.3362
PubMed: 24013700
Links to Exploration step
pubmed:24013700Le document en format XML
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Katze</name></author><author><name sortKey="Munster, Vincent J" sort="Munster, Vincent J" uniqKey="Munster V" first="Vincent J" last="Munster">Vincent J. Munster</name></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name></author></analytic><series><title level="j">Nature medicine</title><idno type="eISSN">1546-170X</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (therapeutic use)</term><term>Coronavirus (physiology)</term><term>Coronavirus Infections (drug therapy)</term><term>Interferon alpha-2</term><term>Interferon-alpha (therapeutic use)</term><term>Macaca mulatta</term><term>Real-Time Polymerase Chain Reaction</term><term>Recombinant Proteins (therapeutic use)</term><term>Ribavirin (therapeutic use)</term><term>Virus Replication</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>Interferon-alpha</term><term>Recombinant Proteins</term><term>Ribavirin</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Interferon alpha-2</term><term>Macaca mulatta</term><term>Real-Time Polymerase Chain Reaction</term><term>Virus Replication</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24013700</PMID><DateCompleted><Year>2013</Year><Month>12</Month><Day>16</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>28</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1546-170X</ISSN><JournalIssue CitedMedium="Internet"><Volume>19</Volume><Issue>10</Issue><PubDate><Year>2013</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Nature medicine</Title><ISOAbbreviation>Nat. Med.</ISOAbbreviation></Journal><ArticleTitle>Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.</ArticleTitle><Pagination><MedlinePgn>1313-7</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/nm.3362</ELocationID><Abstract><AbstractText>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. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Falzarano</LastName><ForeName>Darryl</ForeName><Initials>D</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Wit</LastName><ForeName>Emmie</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Rasmussen</LastName><ForeName>Angela L</ForeName><Initials>AL</Initials></Author><Author ValidYN="Y"><LastName>Feldmann</LastName><ForeName>Friederike</ForeName><Initials>F</Initials></Author><Author 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