title: The cyanobacterial lectin scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus.
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.
authors.affiliation: Department of Viral Therapeutics, Virology Division, United States Army Medical Research Institute of Infectious Disease, Ft. Detrick, Frederick, MD 21702, United States.
authors.forename: Aura R
authors.initials: AR
authors.lastname: Garrison
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Giomarelli
authors.affiliation: Department of Viral Therapeutics, Virology Division, United States Army Medical Research Institute of Infectious Disease, Ft. Detrick, Frederick, MD 21702, United States.
authors.forename: Calli M
authors.initials: CM
authors.lastname: Lear-Rooney
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States; Basic Science Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States.
authors.forename: Carrie J
authors.initials: CJ
authors.lastname: Saucedo
authors.affiliation: Office of the Chief Scientist, Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Frederick, MD 2170, United States.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Yellayi
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States; Basic Science Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States.
authors.forename: Lauren R H
authors.initials: LR
authors.lastname: Krumpe
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States.
authors.forename: Maura
authors.initials: M
authors.lastname: Rose
authors.affiliation: Department of Viral Therapeutics, Virology Division, United States Army Medical Research Institute of Infectious Disease, Ft. Detrick, Frederick, MD 21702, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Paragas
authors.affiliation: Department of Viral Therapeutics, Virology Division, United States Army Medical Research Institute of Infectious Disease, Ft. Detrick, Frederick, MD 21702, United States; Division of Clinical Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Mike
authors.initials: M
authors.lastname: Bray
authors.affiliation: Department of Viral Therapeutics, Virology Division, United States Army Medical Research Institute of Infectious Disease, Ft. Detrick, Frederick, MD 21702, United States.
authors.forename: Gene G
authors.initials: GG
authors.lastname: Olinger
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States.
authors.forename: James B
authors.initials: JB
authors.lastname: McMahon
authors.affiliation: Department of Viral Therapeutics, Virology Division, United States Army Medical Research Institute of Infectious Disease, Ft. Detrick, Frederick, MD 21702, United States.
authors.forename: John
authors.initials: J
authors.lastname: Huggins
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States. Electronic address: okeefeba@mail.nih.gov.
authors.forename: Barry R
authors.initials: BR
authors.lastname: O'Keefe
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000187:drug effects* / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control / Q000821:virology; D020128:Inhibitory Concentration 50; D007279:Injections, Subcutaneous; D037102:Lectins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000821:virology; D029024:Marburgvirus / Q000187:drug effects; D008565:Membrane Proteins; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D044967:Serum / Q000821:virology; D013154:Spleen / Q000821:virology; D016019:Survival Analysis; D014759:Viral Envelope Proteins / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D037102:Lectins; D008565:Membrane Proteins; D014759:Viral Envelope Proteins; C474342:scytovirin protein, S varium
keywords: Cyanobacteria; Ebola; Lectin; Natural product; Scytovirin