Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus.
Ebola virus (Ebo) causes severe hemorrhagic fever and high mortality in humans. There are currently no effective therapies. Here, we have explored potential anti-Ebo activity of the human immunodeficiency virus (HIV)-inactivating protein cyanovirin-N (CV-N). CV-N is known to potently inhibit the infectivity of a broad spectrum of HIV strains at the level of viral entry. This involves CV-N binding to N-linked high-mannose oligossacharides on the viral glycoprotein gp120. The Ebola envelope contains somewhat similar oligosaccharide constituents, suggesting possible susceptibility to inhibition by CV-N. Our initial results revealed that CV-N had both in vitro and in vivo antiviral activity against the Zaire strain of the Ebola virus (Ebo-Z). Addition of CV-N to the cell culture medium at the time of Ebo-Z infection inhibited the development of viral cytopathic effects (CPEs). CV-N also delayed the death of Ebo-Z-infected mice, both when given as a series of daily subcutaneous injections and when the virus was incubated ex vivo together with CV-N before inoculation into the mice. Furthermore, similar to earlier results with HIV gp120, CV-N bound with considerable affinity to the Ebola surface envelope glycoprotein, GP(1,2). Competition experiments with free oligosaccharides were consistent with the view that carbohydrate-mediated CV-N/GP(1,2) interactions involve oligosaccharides residing on the Ebola viral envelope. Overall, these studies broaden the range of viruses known to be inhibited by CV-N, and further implicate carbohydrate moieties on viral surface proteins as common viral molecular targets for this novel protein.
Barrientos
Laura G
LG
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
O'Keefe
Barry R
BR
Bray
Mike
M
Sanchez
Anthony
A
Gronenborn
Angela M
AM
Boyd
Michael R
MR
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D029043:Ebolavirus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D014764:Viral Proteins; C107733:cyanovirin N