Novel small molecule treatment for alpha virus infections and toxic shock

The Army seeks licensees interested in developing a novel small molecule inhibitor of MyD88

Medical & Biotechnology

Alpha viruses such as Venezuelan Equine Encephalitis Virus (VEEV) and Eastern Equine Encephalitis Virus (EEEV) represent a significant public health threat as both emerging infectious diseases and potential bio-terror agents due to their morbidity and mortality in humans, high infectivity in aerosols, considerable stability, and ease of production.  Myeloid differentiation primary response protein 88 (MyD88) plays a critical role in the activation of the host pattern recognition receptors Toll-like receptors (TLRs) and induction of host pro-inflammatory response.  However, during viral infections, MyD88 does not allow the host to properly activate antiviral immune responses.

Researchers at the United States Army Medical Research Institute for Infectious Diseases (USAMRIID) and Scripps Research Institute have developed a novel small molecule compound (called “4210”) that effectively blocks MyD88 signaling.  The compound reduced 3 to 4 log the EEEV and VEEV replication in infected U87 cells.  In addition, 4210 blocked MyD88-mediated pro-inflammatory signaling and protected mice from toxic shock induced death upon lethal exposure to staphylococcal enterotoxin B (SEB).

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