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Antiviral Res ; 112: 1-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25265598

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.


Subject(s)
Antiviral Agents/therapeutic use , Bacterial Proteins/therapeutic use , Carrier Proteins/therapeutic use , Ebolavirus/drug effects , Lectins/therapeutic use , Viral Envelope Proteins/metabolism , Virus Replication/drug effects , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Bacterial Proteins/administration & dosage , Bacterial Proteins/metabolism , Bacterial Proteins/pharmacology , Carrier Proteins/administration & dosage , Carrier Proteins/metabolism , Carrier Proteins/pharmacology , Disease Models, Animal , Ebolavirus/physiology , Glycoproteins/metabolism , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/virology , Inhibitory Concentration 50 , Injections, Subcutaneous , Lectins/administration & dosage , Lectins/metabolism , Lectins/pharmacology , Liver/virology , Marburgvirus/drug effects , Membrane Proteins , Mice, Inbred BALB C , Microbial Sensitivity Tests , Serum/virology , Spleen/virology , Survival Analysis , Viral Load
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