Antiviral Activity of a Small-Molecule Inhibitor of Filovirus Infection
Abstract
There exists an urgent need to develop licensed drugs and vaccines for the treatment or prevention of filovirus infections. FGI-103 is a low-molecular-weight compound that was discovered through an in vitro screening assay utilizing a variant of Zaire ebolavirus (ZEBOV) that expresses green fluorescent protein. In vitro analyses demonstrated that FGI-103 also exhibits antiviral activity against wild-type ZEBOV and Sudan ebolavirus, as well as Marburgvirus (MARV) strains Ci67 and Ravn. In vivo administration of FGI-103 as a single intraperitoneal dose of 10 mg/kg delivered 24 h after infection is sufficient to completely protect mice against a lethal challenge with a mouse-adapted strain of either ZEBOV or MARV-Ravn. In a murine model of ZEBOV infection, delivery of FGI-103 reduces viremia and the viral burden in kidney, liver, and spleen tissues and is associated with subdued and delayed proinflammatory cytokine responses and tissue pathology. Taken together, these results identify a promising antiviral therapeutic candidate for the treatment of filovirus infections.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2010
- Accession Number
- ADA519550
Entities
People
- Abdul S. Yunus
- Gordon T. Ruthel
- Jay Wells
- Kelly Lyn Warfield
- M. J. Aman
- Mark Smith
- Michael Goldblatt
- Michael S. Kinch
- Sina Bavari
- Sven Enterlein
- Travis K. Warren
Organizations
- United States Army Medical Research Institute of Infectious Diseases