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Broad-Spectrum Antiviral Effective Against Ebola, MERS-CoV

Marburg FilovirusBioCryst Pharmaceuticals, Inc. this week announced the online publication in the journal Nature of extensive laboratory and nonclinical characterizations of broad-spectrum antiviral BCX4430, including efficacy results in animal models of infection with Marburg virus and Ebola virus. 

The Nature publication 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. 

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 Disease Control and Prevention. 

BCX4430 completely protected cynomolgus macaques from Marburg virus infection when administered by intramuscular injection 48 hours post-infection. Post-exposure intramuscular administration of BCX4430 also protected rodents against Marburg virus 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).

“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 priority for the U.S. Government.” 

Developed by BioCryst, BCX4430 has demonstrated antiviral activity in testing conducted at BioCryst, Utah State University/NIAID and USAMRIID. BCX4430 has been shown to be active against more than 20 RNA viruses in nine different families, including filoviruses, togaviruses, bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses and flaviviruses. In tests conducted at USAMRIID, BCX4430 protected animals against parenteral exposures to Marburg, Ebola and Rift Valley Fever viruses and from exposures to aerosolized Marburg virus, an experimental condition designed to mimic an exposure scenario that could result during a bioterrorist attack. 

“With its broad-spectrum antiviral activity, attractive drug-like characteristics and demonstrated efficacy against filoviruses, BCX4430 is well-positioned for continued development as a valuable addition to the nation’s arsenal of medical countermeasures,” said Dr. William P. Sheridan, Chief Medical Officer at BioCryst. “A single broad-spectrum agent that treats a range of RNA virus threats, such as BCX4430, presents an efficient one-drug, multi-bug strategic option against high-priority pathogens for the U.S. Government and offers promise as a treatment for patients infected in natural outbreaks.”

BCX4430 is being developed as a countermeasure against human filovirus diseases and other viral diseases representing major public health threats. In September 2013, the National Institute of Allergy and Infectious Diseases (NIAID) contracted with BioCryst for the development of BCX4430 as a treatment for Marburg virus disease. In 2013, NIAID awarded funding of $7.5 million to BioCryst, and total funding of up to $22.0 million, if all contract options are exercised. The goals of this contract are to file investigational new drug (IND) applications for intravenous and intramuscular BCX4430 for the treatment of Marburg virus disease, and to conduct Phase 1 human clinical trials.

Read more at Nature: Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430.

Source: Adapted from BioCryst Pharmaceuticals

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