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Marburg virus, like other filoviruses, causes hemorrhagic fever and has a fatality rate as high as 90%. Filoviruses are normally transmitted between individuals by blood or body fluids but are also infectious in aerosol form, which means they pose the risk of becoming a global health threat as well as being used as agents of biological warfare or terrorism. Given these possibilities, the lack of vaccines or therapies for filovirus infection is a great concern. Developing filovirus countermeasures is a top priority for the US Army Medical Research Institute of Infectious Diseases (USAMRIID; Fort Detrick, MD), said USAMRIID commander Col. Erin P. Edgar in a press release, and USAMRIID scientists recently reported new progress toward achieving that goal.

The group, led by Sina Bavari, showed that a synthetic small-molecule inhibitor of viral RNA polymerase activity, called BCX4430, protected cynomolgus macaques from Marburg virus infection without adverse effects (Nature doi:10.1038/nature13027; published online 2 March 2014). The drug was administered intramuscularly and was effective even when administered up to 48 h after exposure to Marburg virus. These characteristics make it potentially suitable for use during outbreaks.

Guinea pigs exposed to Marburg virus either by intraperitoneal injection or by aerosol inhalation were also protected from infection by administration of BCX4430 within 48 h of exposure. BCX4430 also showed efficacy against other filoviruses, including Ravn virus and Ebola virus, as well as Rift Valley fever virus (belonging to the related family of bunyaviruses) in rodents. Intramuscular administration of BCX4430 protected mice from all three of these viruses, and oral administration was also effective against Ebola virus infection in mice. In cell-based studies, BCX4430 showed specific antiviral activity against multiple virus families other than filoviruses and bunyaviruses, including arenaviruses, orthomyxoviruses, picornaviruses, paramyxoviruses, flaviviruses and coronaviruses. The researchers are carrying out further studies to evaluate the in vivo efficacy of BCX4430 against these and other virulent viral pathogens.

BCX4430 was developed by BioCryst Pharmaceuticals, Inc., in collaboration with the USAMRIID scientists. It inhibits viral RNA polymerase activity indirectly after being incorporated into viral RNA strands, causing premature termination of transcription and replication. Col. Edgar indicated that the study “demonstrates the importance of government-industry collaboration,” continuing, “[w]hen federal assets like USAMRIID team up with cutting-edge partners in private industry, we can make real progress.”