Cyanovirin-N
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Cyanovirin-N (CV-N) is a protein produced by the cyanobacterium Nostoc ellipsosporum that displays virucidal activity against several viruses, including human immunodeficiency virus (HIV).[1] A cyanobacterial protein called cyanovirin-N (CV-N) has strong anti-human immunodeficiency virus (HIV) neutralizing properties.[2] The virucidal activity of CV-N is mediated through specific high-affinity interactions with the viral surface envelope glycoproteins gp120 and gp41, as well as to high-mannose oligosaccharides found on the HIV envelope.[3] In addition, CV-N is active against rhinoviruses, human parainfluenza virus, respiratory syncytial virus, and enteric viruses. The virucidal activity of CV-N against influenza virus is directed towards viral haemagglutinin.[4]
The blue-green alga Nostoc ellipsosporum naturally contains the protein cyanovirin-N. The National Cancer Institute (NCI) in the United States carried out the initial isolation and characterisation of this protein in 1999.[5] The use of cyanovirin-N as an antiviral drug, particularly against HIV, has since been the subject of investigation. Its ability to bind to the HIV-encapsulating glycoprotein gp120 has been demonstrated in several studies, which has led to the development of Cyanovirin-N-based therapies and preventatives.[5]
Structure
[edit]Cyanovirin-N is a lengthy, mostly beta-sheet protein that displays internal two-fold pseudosymmetry. The fundamental atomic root-mean-square of the two sequence repeats (1-50 and 51-101) differs by 1.3 A while sharing 32% of the same sequence. The total fold depends on a number of interactions between the two repetitions, therefore they don't actually belong in separate domains.[6] CV-N has a complex fold composed of a duplication of a tandem repeat of two homologous motifs comprising three-stranded beta-sheet and beta-hairpins.[7]
References
[edit]- ^ Zappe H, Snell ME, Bossard MJ (2008). "PEGylation of cyanovirin-N, an entry inhibitor of HIV". Adv. Drug Deliv. Rev. 60 (1): 79–87. doi:10.1016/j.addr.2007.05.016. PMID 17884238.
- ^ Dey, Barna, Danica L. Lerner, Paolo Lusso, Michael R. Boyd, John H. Elder, and Edward A. Berger. “Multiple Antiviral Activities of Cyanovirin-N: Blocking of Human Immunodeficiency Virus Type 1 gp120 Interaction with CD4 and Coreceptor and Inhibition of Diverse Enveloped Viruses.” Journal of Virology 74, no. 10 (2000): 4562–69. https://doi.org/10.1128/jvi.74.10.4562-4569.2000.)
- ^ Botos I, Wlodawer A (February 2003). "Cyanovirin-N: a sugar-binding antiviral protein with a new twist". Cell. Mol. Life Sci. 60 (2): 277–87. doi:10.1007/s000180300023. PMC 11138712. PMID 12678493. S2CID 10579615.
- ^ O'Keefe BR, Smee DF, Turpin JA, Saucedo CJ, Gustafson KR, Mori T, Blakeslee D, Buckheit R, Boyd MR (August 2003). "Potent anti-influenza activity of cyanovirin-N and interactions with viral hemagglutinin". Antimicrob. Agents Chemother. 47 (8): 2518–25. doi:10.1128/aac.47.8.2518-2525.2003. PMC 166092. PMID 12878514.
- ^ a b Boyd, MR; Gustafson, KR; McMahon, JB; Shoemaker, RH; O'Keefe, BR; et al. (June 1997). "Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development". Antimicrobial Agents and Chemotherapy. 41 (6): 1521–1530. doi:10.1128/AAC.41.7.1521. PMC 163952. PMID 9210678.
{{cite journal}}: CS1 maint: numeric names: authors list (link) - ^ Bewley, C.; Gustafson, K.; Boyd, M.; Covell, D.G.; Bax, A.; Clore, G.M.; Gronenborn, A.M. (1998). "Solution structure of cyanovirin-N, a potent HIV-inactivating protein". Nature Structural and Molecular Biology. 5 (7): 571–578. doi:10.1038/828. PMID 9665171. S2CID 11367037.
- ^ Botos I, O'Keefe BR, Shenoy SR, Cartner LK, Ratner DM, Seeberger PH, Boyd MR, Wlodawer A (September 2002). "Structures of the complexes of a potent anti-HIV protein cyanovirin-N and high mannose oligosaccharides". J. Biol. Chem. 277 (37): 34336–42. doi:10.1074/jbc.M205909200. PMID 12110688.
External links
[edit]- Article on using Tobacco Plants to produce Cyanovirin—BBC News
- Woodrum, BW; Maxwell, J; Allen, DM; et al. (6 June 2016). "A Designed 'Nested' Dimer of Cyanovirin-N Increases Antiviral Activity". Viruses. 8 (6): 158. doi:10.3390/v8060158. PMC 4926178. PMID 27275831.