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Military Seeks Support for Arenaviruses Countermeasures

Virions of an arenavirus, a cause of fatal hemorrhagic fever. Credit: CDC

The U.S. Army Medical Research Acquisition Activity (USAMRIID) is seeking research services to develop mechanisms of action for FDA-approved drugs against arenaviruses.

The Virology Division within USAMRIID has screened a library containing approximately 3,200 FDA-approved drugs to identify ones that inhibit infections by multiple pathogenic viruses including six hemorrhagic fever viruses and four alphaviruses:

  • Ebolavirus
  • Marburgvirus
  • Dengue Virus
  • West Nile Virus
  • Lassa Fever Virus
  • Rift Valley Fever Virus
  • Western Equine Encephalitis
  • Eastern Equine Encephalitis
  • Venezuelan Encephalitis
  • Chikungunya

From this effort, USAMRIID has identified approximately 140 highly active anti-viral lead therapeutic (HALLT) compounds that block infection by members of two or more virus families. Understanding the mechanism of action (MOA) will help USAMRIID understand how these compounds may be inhibiting infection and at which stage of virus replication, in order to develop more effective therapeutics.

Previous efforts against filoviruses have focused on specifically designed Ebolavirus (EBOV) virus like particles (VLPs) that recapitulate the filamentous shape and entry properties of authentic EBOV through the incorporation of the EBOV glycoprotein (GP).

Similar to other enveloped viruses, it is the GP that dictates all aspects of virus entry. Additionally, these VLPs incorporate two engineered forms of EBOV VP40, one tagged with β-lactamase and one tagged with mCherry. VP40 directs the assembly of EBOV VLPs, similar to authentic virus. The β-lactamase VP40 acts as a reporter when the VLPs have fused with a cellular membrane and have entered into the cytoplasma, whereas the mCherry VP40 provides a fluorescent tag for visualizing the VLPs during cellular entry.

The required work is to develop a similar pseudovirion assay for arenaviruses and identify the mechanism of action of compounds identified in the authentic virus screens completed by USAMRIID.

Further details are requirements are detailed under Solicitation Number: W81XWH-15-T-0065. Questions must be submitted by Dec. 17, 2014. The response deadline is Jan. 8, 2015.

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