Sunday, September 08, 2013

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

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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 Branswells 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 vitro6; 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 . . . )