Literature DB >> 25265598

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

Aura R Garrison1, Barbara G Giomarelli2, Calli M Lear-Rooney1, Carrie J Saucedo3, Srikanth Yellayi4, Lauren R H Krumpe3, Maura Rose2, Jason Paragas1, Mike Bray5, Gene G Olinger1, James B McMahon2, John Huggins1, Barry R O'Keefe6.   

Abstract

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 min, but was cleared within 4h. When ZEBOV-infected mice were given 30 mg/kg/day of SVN by subcutaneous injection every 6h, 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. Published by Elsevier B.V.

Entities:  

Keywords:  Cyanobacteria; Ebola; Lectin; Natural product; Scytovirin

Mesh:

Substances:

Year:  2014        PMID: 25265598      PMCID: PMC4258435          DOI: 10.1016/j.antiviral.2014.09.012

Source DB:  PubMed          Journal:  Antiviral Res        ISSN: 0166-3542            Impact factor:   5.970


  24 in total

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3.  Plaque assay for Ebola virus.

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4.  Overexpression and purification of scytovirin, a potent, novel anti-HIV protein from the cultured cyanobacterium Scytonema varium.

Authors:  Changyun Xiong; Barry R O'Keefe; Istvan Botos; Alexander Wlodawer; James B McMahon
Journal:  Protein Expr Purif       Date:  2005-10-24       Impact factor: 1.650

5.  Ebolavirus delta-peptide immunoadhesins inhibit marburgvirus and ebolavirus cell entry.

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10.  Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor.

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6.  Hepatitis C Virus Resistance to Carbohydrate-Binding Agents.

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7.  Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins.

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8.  Novel Antifungal Activity for the Lectin Scytovirin: Inhibition of Cryptococcus neoformans and Cryptococcus gattii.

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Review 9.  Antiviral lectins: Selective inhibitors of viral entry.

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Review 10.  Cationic host defense peptides; novel antimicrobial therapeutics against Category A pathogens and emerging infections.

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