Military Contracts Encourage Development of Drugs to Treat Hemorrhagic Fever Viruses

The possible weaponization of these viruses and their potential use by terrorist organizations has induced the [U.S.] Defense Threat Reduction Agency (Fort Belvoir, VA, USA) to award a series of contracts for development of antiviral agents for treatment of hemorrhagic fever viruses

Each company is using its own proprietary technology to develop effective drug candidates. AVI BioPharma (Portland, OR, USA) is applying its "Neugene” antisense technology to develop synthetic compounds able to selectively bind to and inhibit viral genes.

Alnylam Pharmaceuticals (Cambridge, MA, USA) focuses on the application of RNAi technology for the development of antiviral drugs. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. RNAi therapeutics target the root genetic cause of diseases by potently silencing specific messenger RNA, thereby preventing the disease-causing proteins from being made.

Functional Genetics Inc. (Rockville, MD, USA) is concentrating primarily on drugs to counter the activity of a compound called TSG101. Retroviruses begin their infectious life cycle by binding to cell surface proteins, an adhesion that promotes fusion of the viral and cell membranes and entry of the viral genome into the cell. The RNA-based viral genome replicates and, after integrating into a host chromosome, directs the production of new viral RNA and proteins. These viral components then self-assemble and escape from the cell as mature viral progeny. From adhesion to escape, the infectious cycle requires the concerted activity of viral and cellular proteins. One such cellular protein is TSG101. To propagate, fully assembled viruses must bud and pinch off membranous material from the cell surface. It has been shown that viruses are unable to carry out this final stage of maturation, and therefore recruit TSG101 and other cellular proteins for assistance. Inhibition of TSG101 activity would prevent viral replication.

Normally the small potential market in the developed countries for drugs against hemorrhagic fever virus would practically guarantee that they would not be developed. However, the importance of such drugs to the military is indicated by the size of the contracts that have been awarded: Alnylam Pharmaceuticals - US$10.9 million, Functional Genetics Inc. - $13 million, and AVI BioPharma - $28 million.

These amounts are only enough to get the ball rolling, however. Drug development is a long and expensive process ($100 million is often mentioned a minimum amount to get a drug through approvals), and promising therapies do not all make it through the research and testing stages. At best, it will be many years before an effective agent against Ebola or Marburg virus will be available.


Related Links:
Defense Threat Reduction Agency
AVI BioPharma
Alnylam Pharmaceuticals