Antiviral Activity of a Small-Molecule Inhibitor of Filovirus Infection

Warren, Travis K.; Warfield, Kelly L.; Wells, Jay; Enterlein, Sven; Smith, Mark A.; Ruthel, Gordon; Yunus, Abdul S.; Kinch, Michael S.; Goldblatt, Michael; Aman, M. Javad; Bavari, Sina

doi:10.1128/aac.01315-09

Cited by 67 publications

(50 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A green fluorescent protein (GFP)-Ebola virus-based highthroughput screening assay identified FGI-103 as an effective Ebola virus replication inhibitor (90% effective concentration, 330 nM) with no apparent in vitro cytotoxicity over the compound concentration range tested (72). Prophylactic administration (1 h before Ebola virus infection) of FGI-103 to C57BL/6 mice resulted in 100% protection.…”

Section: Small-molecule Inhibitors Of Ebola Virus Infectionmentioning

confidence: 99%

Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks

Haque

Hober

Blondiaux³

2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

c Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre-and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients.

show abstract

Section: Small-molecule Inhibitors Of Ebola Virus Infectionmentioning

confidence: 99%

Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks

Haque

Hober

Blondiaux³

2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…2 The Western switch to ''Musoke'' most likely occurred because its history and origin were known, whereas the history of the 1967 variant often involved passaging to various extents in rodents without adequately keeping track of which partner institution received which particular isolate. Recently, a few U.S. groups reported the use of a MARV Cieplik-derived isolate (see, eg, refs [15][16][17][18][19].…”

Section: Marburgvirus Isolates Used In Researchmentioning

confidence: 99%

Evaluation of Perceived Threat Differences Posed by Filovirus Variants

Kuhn

Dodd

Wahl‐Jensen

et al. 2011

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, an

Self Cite

View full text Add to dashboard Cite

show abstract

“…Scytovirin (SVN) was produced in E. coli and purified as previously described (Xiong et al 2006). All protein samples were diluted to a final concentration of 1 mg/ml in PBS, as determined by amino acid analysis, and sterile-filtered before use.…”

Section: Methodsmentioning

confidence: 99%

The cyanobacterial lectin scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus

et al. 2014

View full text Add to dashboard Cite

The cyanobacterial lectin scytovirin (SVN) binds with high affinity to mannose-rich oligosaccharides on the envelope glycoprotein (GP) of a number of viruses, blocking entry into target cells. In this study, we assessed the ability of SVN to bind to the envelope GP of Zaire Ebola virus (ZEBOV) and inhibit its replication. SVN interacted specifically with the protein’s mucin-rich domain. In cell culture, it inhibited ZEBOV replication with a 50% virus-inhibitory concentration (EC50) of 50 nM, and was also active against the Angola strain of the related Marburg virus (MARV), with a similar EC50. Injected subcutaneously in mice, SVN reached a peak plasma level of 100 nm in 45 minutes, but was cleared within 4 hours. When ZEBOV-infected mice were given 30 mg/kg/day of SVN by subcutaneous injection every 6 hours, beginning the day before virus challenge, 9 of 10 animals survived the infection, while all infected, untreated mice died. When treatment was begun one hour or one day after challenge, 70-90% of mice survived. Quantitation of infectious virus and viral RNA in samples of serum, liver and spleen collected on days 2 and 5 postinfection showed a trend toward lower titers in treated than control mice, with a significant decrease in liver titers on day 2. Our findings provide further evidence of the potential of natural lectins as therapeutic agents for viral infections.

show abstract

Antiviral Activity of a Small-Molecule Inhibitor of Filovirus Infection

Cited by 67 publications

References 22 publications

Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks

Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks

Evaluation of Perceived Threat Differences Posed by Filovirus Variants

The cyanobacterial lectin scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus

Contact Info

Product

Resources

About