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Nature Medicine. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV?infected rhesus macaques

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  • Nature Medicine. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV?infected rhesus macaques

    [Source: Nature, full page: (LINK): Abstract, edited.]


    Medicine | Letter

    Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV?infected rhesus macaques


    Darryl Falzarano,<SUP>1 </SUP>Emmie de Wit,<SUP>1 </SUP>Angela L Rasmussen,<SUP>2 </SUP>Friederike Feldmann,<SUP>3 </SUP>Atsushi Okumura,<SUP>2 </SUP>Dana P Scott,<SUP>3 </SUP>Doug Brining,<SUP>3 </SUP>Trenton Bushmaker,<SUP>4 </SUP>Cynthia Martellaro,<SUP>1 </SUP>Laura Baseler,<SUP>1, 5 </SUP>Arndt G Benecke,<SUP>2, 6 </SUP>Michael G Katze,<SUP>2, 7 </SUP>Vincent J Munster<SUP>4 </SUP>& Heinz Feldmann<SUP>1, 8</SUP>
    <SUP></SUP>
    Journal name: Nature Medicine - Year published: (2013) - DOI: doi:10.1038/nm.3362

    Received 24 May 2013 - Accepted 27 August 2013 - Published online 08 September 2013


    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<SUP>1</SUP> 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<SUP>2, 3</SUP> that recapitulates mild to moderate human MERS-CoV cases<SUP>4, 5</SUP>. The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro<SUP>6</SUP>; 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.


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  • #2
    Re: Nature Medicine. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV?infected rhesus macaques

    Nature: Animal Testing Of Drug Combo Shows Potential For Treating MERS



    Coronavirus ? Credit CDC PHIL


    # 7743



    One of the more worrisome aspects of the recent emergence of MERS coronavirus has been the lack of a specific and effective treatment. Unlike influenza, there are currently no coronavirus-specific antivirals available.
    Treatment has basically been supportive (e.g. fluids, vasopressors, ventilators and/or ECMO, dialysis, and antibiotics for secondary infections).
    Today, in a letter that appears in Nature Medicine, we learn that a drug combination (Interferon-α2b & ribavirin) ? which showed promise earlier in the year in in-vitro experiments - `reduces virus replication, moderates the host response, and improves the clinical outcome? of rhesus macaques experimentally infected with the MERS coronavirus.

    While welcome news, a few caveats are in order.

    • First, the macaque model is not a perfect substitute for humans, as they tend not to be as severely impacted by the MERS virus.
    • Second, treatment was initiated 8 hours post infection, which is an earlier pharmacological intervention than most humans could hope to see.
    • And third, most severe human infections have been seen in people with co-morbidities like COPD, cancer, diabetes, asthma . . . variables this study does not attempt to replicate.


    Still, this has to be seen as progress. I?ve a link to the Abstract, a brief announcement from NIAID, then a link to Helen Branswell?s article on this announcement.
    Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV?infected rhesus macaques

    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 Feldmann
    ABSTRACT (Excerpt)
    The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro<sup>6</sup>; 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.
    From NIAID:
    Sunday, September 8, 2013
    MERS-CoV Treatment Effective in Monkeys, NIH Study Finds
    WHAT:

    National Institutes of Health (NIH) scientists report that a combination of two licensed antiviral drugs reduces virus replication and improves clinical outcome in a recently developed monkey model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Their study, which appears as a letter in the Sept. 8 edition of Nature Medicine, expands on work published in April showing that a combination of ribavirin and interferon-alpha 2b stops MERS-CoV from replicating in cell culture. Both antivirals are routinely used together to treat viral diseases such as hepatitis C.

    In the latest study, investigators at NIH?s National Institute of Allergy and Infectious Diseases (NIAID) infected six rhesus macaques with MERS-CoV and, eight hours later, treated half of them with the two-drug regimen. Compared to the untreated animals, the treatment group showed no breathing difficulties and only minimal X-ray evidence of pneumonia. The treated animals also had lower amounts of virus and less severe tissue damage in the lungs.

    As of Aug. 30, 2013, the World Health Organization has reported 108 human cases of MERS-CoV infection, including 50 deaths. Given the current lack of treatment options, the authors of this study conclude that combined ribavirin and interferon-alpha 2b therapy should be considered as an early intervention.
    (Continue . . . )
    And finally, from Helen Branswell, a detailed and informative report, with comments from Matthew Frieman, Professor of Virology at the University of Maryland medical school in Baltimore.
    Drug combo helps reduce MERS virus in animals: study

    Helen Branswell, The Canadian Press
    Published Sunday, September 8, 2013 1:16PM EDT

    TORONTO -- New research is adding weight to the idea that a combination of existing drugs may help some patients infected with the new MERS coronavirus.

    The findings could prove to be important because there is no vaccine to prevent the infection and no drugs specifically designed to mitigate the damage it does in severe cases.

    Infections with the new virus continue to pile up, particularly in Saudi Arabia.

    (Continue . . . )
    Posted by Michael Coston at <a class="timestamp-link" href="http://afludiary.blogspot.com/2013/09/nature-animal-testing-of-drug-combo.html" rel="bookmark" title="permanent link"><abbr class="published" title="2013-09-08T14:34:00-04:00">2:34 PM</abbr>

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