Format

Send to

Choose Destination
Antiviral Res. 2014 Dec;112:1-7. doi: 10.1016/j.antiviral.2014.09.012. Epub 2014 Oct 5.

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

Author information

1
Department of Viral Therapeutics, Virology Division, United States Army Medical Research Institute of Infectious Disease, Ft. Detrick, Frederick, MD 21702, United States.
2
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.
3
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.
4
Office of the Chief Scientist, Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Frederick, MD 2170, United States.
5
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.
6
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.

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.

KEYWORDS:

Cyanobacteria; Ebola; Lectin; Natural product; Scytovirin

PMID:
25265598
PMCID:
PMC4258435
DOI:
10.1016/j.antiviral.2014.09.012
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center