Cyanovirin-N: a sugar-binding antiviral protein with a new twist

  title={Cyanovirin-N: a sugar-binding antiviral protein with a new twist},
  author={Istvan Botos and Alexander Wlodawer},
  journal={Cellular and Molecular Life Sciences CMLS},
Abstract. Cyanovirin-N (CV-N), an 11-kDa protein from the cyanobacterium Nostoc ellipsosporum, is a highly potent virucidal agent that has generated interest as a lead natural product for the prevention and chemotherapy of human immunodeficiency virus infection. The antiviral activity of CV-N is mediated through specific, high-affinity interactions with the viral surface envelope glycoproteins. A number of structures of wild-type, mutant and sequence-shuffled CV-N have been solved by nuclear… 
A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity.
Findings show that the presence of at least two oligomannoside-binding sites, either by the existence of intact domains A and B or by formation of domain-swapped dimers, is essential for activity.
The antiviral lectin cyanovirin-N: probing multivalency and glycan recognition through experimental and computational approaches.
An integrated approach that encompasses structural determination, mutagenesis analysis and computational work holds particular promise to clarify aspects of the interactions between CVN and glycans.
Glycan-Cyanovirin-N Interactions and Designed WW Domains: Combining Experimental and Computational Studies
Biophysical calculations completed on a monomeric-stabilized mutant of cyanovirin-N, P51G-m4-CVN, in which domain A binding activity is abolished by four mutations are presented; with comparisons made to CVNmutDB, inwhich domain B binding action is abolished.
Proteins that bind high-mannose sugars of the HIV envelope.
The role of Glu41 in the binding of dimannose to P51G-m4-CVN.
Mutations of P51G-m4-CVN Glu41 to Ala41 and Gly41 reveal that whereas the loss of Coulomb interactions result in a free energy penalty of about 2.1 kcal/mol, this is significantly compensated by favorable contributions to the Lennard-Jones portion of the transformation, resulting in almost no change in the free energy of binding.
In silico improvement of the cyanobacterial lectin microvirin and mannose interaction
The results of an in silico approach to improve affinity interaction between the cyanobacterial lectin microvirin and its ligand Manα(1-2)Man showed that the mutant (Thr82Arg) showed a higher affinity interaction with Manα (1- 2)Man.
Antiviral Cyanometabolites—A Review
The structure and activity of the most promising antiviral cyanobacterial products are presented and provide a good basis for further studies on the therapeutic potential of these microorganisms.
A new lectin from the sea worm Serpula vermicularis: isolation, characterization and anti-HIV activity.


Solution structure of cyanovirin-N, a potent HIV-inactivating protein
The solution structure of cyanovirin-N, a potent 11,000 M r HIV-inactivating protein that binds with high affinity and specificity to the HIV surface envelope protein gp120, has been solved by
Domain-swapped structure of a mutant of cyanovirin-N.
Properties of cyanovirin-N (CV-N): inactivation of HIV-1 by sessile cyanovirin-N (sCV-N).
CV-N binds with extremely high affinity to highly conserved binding site(s) on the viral envelope glycoprotein gp120, preventing virus-to-cell fusion, viral entry and infection of cells, and is undergoing preclinical development for topical anti-HIV prophylactic applications to prevent sexual transmission of HIV.
Engineering an obligate domain-swapped dimer of cyanovirin-N with enhanced anti-HIV activity.
An obligate domain-swapped dimer of cyanovirin-N is constructed that represents a new tetravalent carbohydrate binding protein that is stable over a large range of pH values and can be rapidly obtained in >98% purity in a single chromatographic step.
Solution structure of a cyanovirin-N:Man alpha 1-2Man alpha complex: structural basis for high-affinity carbohydrate-mediated binding to gp120.
The CVN:Manalpha1-2Manalpha complex provides the first high-resolution structure of a mannose-specific protein-carbohydrate complex with nanomolar affinity and presents a new carbohydrate binding motif, as well as a new class of carbohydrate binding protein, that facilitates divalent binding via a monomeric protein.
Crystal structure of cyanovirin-N, a potent HIV-inactivating protein, shows unexpected domain swapping.
The crystal structure of cyanovirin-N (CV-N), a protein with potent antiviral activity, was solved at 1.5 A resolution by molecular replacement using as the search model the solution structure previously determined by NMR, with the exception of the unexpected phenomenon of domain swapping.
Analysis of sequence requirements for biological activity of cyanovirin-N, a potent HIV (human immunodeficiency virus)-inactivating protein.
Findings are consistent with the view that gp120 binding is a necessary but not sufficient requirement for the HIV-inactivating activity of CV-N and related proteins; the sequence specificities for gp120binding and anti-HIV activity are not identical.
Construction and enhanced cytotoxicity of a [cyanovirin-N]-[Pseudomonas exotoxin] conjugate against human immunodeficiency virus-infected cells.
The feasibility of use of CV-N as a gp120-targeting sequence for construction and experimental therapeutic investigations of unique new chimeric toxins designed to selectively destroy HIV-infected host cells is established.
Recombinant production of cyanovirin-N, a potent human immunodeficiency virus-inactivating protein derived from a cultured cyanobacterium.
This recombinant production and purification of a novel anti-human immunodeficiency virus (HIV) protein, cyanovirin-N (CV-N), in Escherichia coli provides a basis for large-scale production of clinical grade CV-N for further research and development as an anti-HIV microbicide.