Infectious Diseases

The global market for influenza therapeutics was estimated at approximately $2 billion in 2004 and has grown to over $4.5 billion over the last year due to the pandemic threat. The current market is divided roughly into a $1.5 billion vaccine market and a $3 billion antiviral market.

The cost to the community of influenza is estimated at $12 billion per year in the US alone.
An anti-influenza therapeutic targeting all influenza subtypes and new variants would be regarded as a major breakthrough in influenza treatment.

Viral replication presents multiple targeting opportunities for RAFT Intervention Technology®. Enveloped viruses in particular utilize RAFTs at several steps of the replication cycle. Employing this mechanism, they create their own RAFTs, resulting in highly specific therapeutic intervention points. Since RAFTs play a role in several stages of viral replication, RAFT intervention could occur at different sites and each by a different pharmaceutical scaffold.

JADO’s lead anti-influenza compound is able to block all major human pathogenic influenza subtypes and is thus a broad-band antiviral. Moreover it is expected to prevent development of viral resistance due to a new mode-of-action – intervention in the lipid structure of the viral budding RAFT. This compound is currently undergoing optimization.

RAFT Dependent Virus Infection Like the host cells they infect, enveloped viruses are surrounded by a lipid membrane, which fuses with the host plasma membrane during viral infection. The infected cell is directed by the virus to make copies of virus proteins and nucleic acids, which are assembled and released back through the plasma membrane. The release of new virus particles involves production of a new virus envelope, and this is a specific lipid RAFT. Virus RAFT proteins, residing in the plasma membrane, self-aggregate and at the same time select the RAFT lipids (shown in red) needed to form the envelope. This is a highly selective process as different virus envelopes have different lipid and protein compositions. Once the enveloped RAFT is formed and the virus core enclosed, the new virus particle complete with its RAFT buds from the membrane. JADO’s RAFT modulator compounds prevent virus budding by interfering in the assemble of the envelope RAFT. These inhibitors are designed to specifically target the virus RAFT, but once incorporated, they prevent the virus from completing the assembly process. The virus can no longer exit the cell and replication is arrested.