title: FGI-104: a broad-spectrum small molecule inhibitor of viral infection.
abstract: The treatment of viral diseases remains an intractable problem facing the medical community. Conventional antivirals focus upon selective targeting of virus-encoded targets. However, the plasticity of viral nucleic acid mutation, coupled with the large number of progeny that can emerge from a single infected cells, often conspire to render conventional antivirals ineffective as resistant variants emerge. Compounding this, new viral pathogens are increasingly recognized and it is highly improbable that conventional approaches could address emerging pathogens in a timely manner. Our laboratories have adopted an orthogonal approach to combat viral disease: Target the host to deny the pathogen the ability to cause disease. The advantages of this novel approach are many-fold, including the potential to identify host pathways that are applicable to a broad-spectrum of pathogens. The acquisition of drug resistance might also be minimized since selective pressure is not directly placed upon the viral pathogen. Herein, we utilized this strategy of host-oriented therapeutics to screen small molecules for their abilities to block infection by multiple, unrelated virus types and identified FGI-104. FGI-104 demonstrates broad-spectrum inhibition of multiple blood-borne pathogens (HCV, HBV, HIV) as well as emerging biothreats (Ebola, VEE, Cowpox, PRRSV infection). We also demonstrate that FGI-104 displays an ability to prevent lethality from Ebola in vivo. Altogether, these findings reinforce the concept of host-oriented therapeutics and present a much-needed opportunity to identify antiviral drugs that are broad-spectrum and durable in their application.
authors: Michael S
authors: MS
authors: Kinch
authors: Abdul S
authors: AS
authors: Yunus
authors: Calli
authors: C
authors: Lear
authors: Hanwen
authors: H
authors: Mao
authors: Hanson
authors: H
authors: Chen
authors: Zena
authors: Z
authors: Fesseha
authors: Guangxiang
authors: G
authors: Luo
authors: Eric A
authors: EA
authors: Nelson
authors: Limin
authors: L
authors: Li
authors: Zhuhui
authors: Z
authors: Huang
authors: Michael
authors: M
authors: Murray
authors: William Y
authors: WY
authors: Ellis
authors: Lisa
authors: L
authors: Hensley
authors: Jane
authors: J
authors: Christopher-Hennings
authors: Gene G
authors: GG
authors: Olinger
authors: Michael
authors: M
authors: Goldblatt