Development of a broad-spectrum antiviral with activity against Ebola virus

Aman, M. Javad; Kinch, Michael S.; Warfield, Kelly L.; Warren, Travis K.; Yunus, Abdul S.; Enterlein, Sven; Stavale, Eric; Wang, Peifang; Chang, Shaojing; Tang, Qingsong; Porter, Kevin R.; Goldblatt, Michael; Bavari, Sina

doi:10.1016/j.antiviral.2009.06.001

Cited by 84 publications

(75 citation statements)

References 20 publications

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“…We observed a range of inhibition using cell-based assays of at least 1 log 10 PFU/mL for ANDV and HTNV to as high as 3.2 log 10 PFU/mL for RVFV. The pharmacokinetic and organ distribution profile of FGI-106 in vivo was previously shown to be sufficient to provide efficacious levels of FGI-106 to organs that are relevant to infection with bunyaviruses (liver, lungs, spleen, and kidneys; 19 ). Consistent with this finding, FGI-106 treatment of animals infected with RVFV was sufficient to delay the onset of disease and protect almost half of individuals from an otherwise lethal infection.…”

Section: Discussionmentioning

confidence: 99%

“…Our in vitro and in vivo results collectively suggest that FGI-106 activity may not entirely be due to antiviral effects, but more of a therapeutic effect. FGI-106 was originally identified using a screen of small-molecule inhibitors of Ebola virus, 19 which is a hemorrhagic fever virus in the family Filoviridae. These studies demonstrated efficacy against Ebola virus as measured in cell-based studies and in vivo in a mouse model of infection.…”

Section: Discussionmentioning

confidence: 99%

“…were collected over the following 6 h. These studies revealed a peak FGI-106 plasma concentration of 286 ng/mL 5 min after dosing and the plasma levels decreased thereafter with an estimated half life of approximately 15 min ( Figure 4A in 19 ). Organs were harvested 6 h after mice received a single 3 mg/kg dose, revealing accumulation of 10 to 40 µg of FGI-106 per g in organs of interest (lungs, liver, kidneys, spleen; Figure 4B in 19 ).…”

Section: Dovepressmentioning

confidence: 99%

“…Organs were harvested 6 h after mice received a single 3 mg/kg dose, revealing accumulation of 10 to 40 µg of FGI-106 per g in organs of interest (lungs, liver, kidneys, spleen; Figure 4B in 19 ). To place these findings in perspective of the results of cell-based studies, the EC 90 value determined with Vero cells translates to 4.4 × 10 -3 µg/g.…”

Section: Dovepressmentioning

confidence: 99%

“…The pharmacokinetics and bioavailability of the molecule in vivo was published previously. 19 These studies were completed using uninfected mice to investigate the pharmacokinetics and organ distribution of FGI-106 to relevant target organs. Specifically, viral hemorrhagic fevers are often characterized by damage to the liver, kidneys, and spleen.…”

Section: Safety and Pharmacokinetic Analyses Of Fgi-106 In Vivomentioning

confidence: 99%

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Development of FGI-106 as a broad-spectrum therapeutic with activity against members of the family Bunyaviridae

Kinch¹

2010

VAAT

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Virus Adaptation and Treatment Abstract:The family Bunyaviridae is a diverse group of negative-strand RNA viruses that infect a wide range of arthropod vectors and animal hosts. Based on the continuing need for new therapeutics to treat bunyavirus infections, we evaluated the potential efficacy of FGI-106, a small-molecular compound that previously demonstrated activity against different RNA viruses. FGI-106 displayed substantial antiviral activity in cell-based assays of different bunyavirus family members, including Asian and South American hantaviruses (Hantaan virus and Andes virus), Crimean-Congo hemorrhagic fever virus, La Crosse virus, and Rift Valley fever virus. The pharmacokinetic profile of FGI-106 revealed sufficient exposure of the drug to critical target organs (lung, liver, kidney, and spleen), which are frequently the sites of bunyavirus replication. Consistent with these findings, FGI-106 treatment delivered via intraperitoneal injection prior to virus exposure was sufficient to delay the onset of Rift Valley fever virus infection in mouse-based models and to enhance survival in the face of an otherwise lethal infection. Altogether, these results suggest a potential opportunity for the use of FGI-106 to treat infections by members of the family Bunyaviridae.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Dovepressmentioning

confidence: 99%

Section: Dovepressmentioning

confidence: 99%

Section: Safety and Pharmacokinetic Analyses Of Fgi-106 In Vivomentioning

confidence: 99%

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Development of FGI-106 as a broad-spectrum therapeutic with activity against members of the family Bunyaviridae

Kinch¹

2010

VAAT

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Perspectives towards antiviral drug discovery against Ebola virus

Mirza

Vanmeert

Ali

et al. 2019

Journal of Medical Virology

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Ebola virus disease (EVD), caused by Ebola viruses, resulted in more than 11 500 deaths according to a recent 2018 WHO report. With mortality rates up to 90%, it is nowadays one of the most deadly infectious diseases. However, no Food and Drug Administration‐approved Ebola drugs or vaccines are available yet with the mainstay of therapy being supportive care. The high fatality rate and absence of effective treatment or vaccination make Ebola virus a category‐A biothreat pathogen. Fortunately, a series of investigational countermeasures have been developed to control and prevent this global threat. This review summarizes the recent therapeutic advances and ongoing research progress from research and development to clinical trials in the development of small‐molecule antiviral drugs, small‐interference RNA molecules, phosphorodiamidate morpholino oligomers, full‐length monoclonal antibodies, and vaccines. Moreover, difficulties are highlighted in the search for effective countermeasures against EVD with additional focus on the interplay between available in silico prediction methods and their evidenced potential in antiviral drug discovery.

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A Cutting‐Edge View on the Current State of Antiviral Drug Development

Clercq

2013

Medicinal Research Reviews

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Prominent in the current stage of antiviral drug development are: (i) for human immunodeficiency virus (HIV), the use of fixed-dose combinations (FDCs), the most recent example being Stribild(TM); (ii) for hepatitis C virus (HCV), the pleiade of direct-acting antivirals (DAAs) that should be formulated in the most appropriate combinations so as to obtain a cure of the infection; (iii)-(v) new strategies (i.e., AIC316, AIC246, and FV-100) for the treatment of herpesvirus infections: herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), respectively; (vi) the role of a new tenofovir prodrug, tenofovir alafenamide (TAF) (GS-7340) for the treatment of HIV infections; (vii) the potential use of poxvirus inhibitors (CMX001 and ST-246); (viii) the usefulness of new influenza virus inhibitors (peramivir and laninamivir octanoate); (ix) the position of the hepatitis B virus (HBV) inhibitors [lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate (TDF)]; and (x) the potential of new compounds such as FGI-103, FGI-104, FGI-106, dUY11, and LJ-001 for the treatment of filoviruses (i.e., Ebola). Whereas for HIV and HCV therapy is aimed at multiple-drug combinations, for all other viruses, HSV, CMV, VZV, pox, influenza, HBV, and filoviruses, current strategies are based on the use of single compounds.

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Development of a broad-spectrum antiviral with activity against Ebola virus

Cited by 84 publications

References 20 publications

Development of FGI-106 as a broad-spectrum therapeutic with activity against members of the family Bunyaviridae

Development of FGI-106 as a broad-spectrum therapeutic with activity against members of the family Bunyaviridae

Perspectives towards antiviral drug discovery against Ebola virus

A Cutting‐Edge View on the Current State of Antiviral Drug Development

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