Monday, May 19, 2014

Stopping a Hemorrhagic Killer: BCX4430

"Filoviruses, such as Ebola and Marburg virus, constitute serious threats to our national defense," said Colonel Erin P. Edgar, commander of USAMRIID. "Development of cost-effective and versatile treatment options to combat these agents remains an unmet medical need and a high biodefense priorityfor the U.S. Government."
See: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13027.html#sthash.6b2rLOfA.dpuf

ebola virus picture
Ebola

"Filoviruses, such as Ebola virus and Marburg virus, are extremely virulent.Case fatality rates associated with filovirus disease outbreaks are the highest reported for any infection, exceeding 90 percent. These pathogens are classified as Category A bioterrorism Agents by the Centers for DiseaseControl and Prevention. BCX4430 completely protected cynomolgus macaques from Marburg virus infection and Ebola virus infections. In addition, BCX4430 was shown to be active in vitro against a broad range of other RNA viruses, including the emerging viral pathogen Middle East Respiratory Syndrome Coronavirus (MERS-CoV)." See: http:..globenewswire.com/news-release/2014/03/03/614909/10070784/en/BioCryst-Announces-Nature-Publication-Demonstrating-Efficacy-of BCX4430-in-a-Non-Human-Primate-Model-of-Filovirus-Infection#sthash.6b2rLOfA.dpuf

Although Cruecell, a Dutch based pharmaceutical firm has been working on an Ebola vaccine candidate for several years and notes on their site that "In experiments conducted in 2004 by the VRC together with the U.S. ArmyMedical Research Institute of Infectious Diseases (USAMRIID), our vaccine candidate confirms single-dose protection of monkeys against Ebola. Our results are distinct from the earlier trials in that our vaccine is based on PER.C6® cells, makind it suitable for large scale manufacturing." (See: http://www.crucell.com/R_and_D-Clinical_Development_Ebola_Vaccine) One is not exclusive to the other and indeed a viable vaccine candidate would be a valuable addition to any national strategic stockpile. However, BCX4430 offers a novel approach with wide 

applications
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BioCryst Pharmaceuticals, Inc. announced on March 3, 2014 in the journalNature extensive laboratory and nonclinical characterizations of BCX4430, "including efficacy results in animal models of infection with Marburg virus and Ebola virus, two highly virulent pathogens responsible for viral hemorrhagic fever diseases. The Nature publication entitled,"Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430," represents the first report of protection of non-human primates from filovirus disease by a small molecule drug, and describes efficacy results generated from an ongoing collaboration between scientists at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and BioCryst." See: http://globenewswire.com/news-release/2014/03/03/614909/10070784/en/BioCryst-Announces-Nature-Publication-Demonstrating-Efficacy-of-BCX4430-in-a-Non-Human-Primate-Model-of-Filovirus-Infection.html#sthash.6b2rLOfA.dpuf "BCX4430, resembles the famous "A" found in DNA: adenosine. (Recall that DNA is made of Adenosine, Thymidine, Cytidine and Guanosine.) The RNA-based filoviruses also use "A" in their genomes. BCX4430, because it resembles "A", can be accidently used by the virus when it is trying to grow inside of our cells. For the virus, this is a fatal mistake. BCX4430 blocks further growth and reproduction." See: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13027.html#sthash.6b2rLOfA.dpuf

While both Crucell and BioCryst offer potentially novel ways of combating filovirus outbreaks, BCX4430 has the advantage of greater application. This is an exciting discovery, not only as a counter-measure for Ebola and other VHF, but the potential application to other highly pathogenic diseases for which we currently have no treatment or preventive medical countermeasures i.e. vaccines. For years, bio-defence drug discovery has endured a one bug one drug approach, but advanced drug discovery means our ability to counter emerging and re-emerging diseases for which their previously was low to no investment incentives, may mean research and development for orphan diseases will become more enticing. The recent outbreak of Ebola in Guinea and Liberia, serves to remind us that emergingand re-emerging diseases continue to pose a global public health threat. The emergence of MERS-CoV and the increasing mortality associated with it mean it  too will likely remain a health concern for years to come. 


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