Antiviral Activity of a Small-Molecule Inhibitor of Filovirus Infection

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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 invitro screening assay utilizing a variant of Zaireebolavirus (ZEBOV) that expresses green fluorescent protein. Invitro analyses demonstrated that FGI-103 also exhibits antiviral activity against wild-type ZEBOV and Sudanebolavirus, as well as Marburgvirus (MARV) strains Ci67 and Ravn. Invivo 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.