PEGylation of cyanovirin–N, an entry inhibitor of HIV

Zappe, H.; Snell, M.E.; Bossard, M.J.

doi:10.1016/j.addr.2007.05.016

Cited by 57HIV Research and TreatmentHIV/AIDS drug development and treatmentAdvanced Drug Delivery Systems

PEGylation of cyanovirin–N, an entry inhibitor of HIV

Zappe, H., Snell, M.E., Bossard, M.J.·2008·Advanced Drug Delivery Reviews

DOI 10.1016/j.addr.2007.05.016

Open this paper in CoChat — free account

Abstract

Cyanovirin-N (CV-N) is a potent inhibitor of human immunodeficiency virus and many other viruses. It has a high potential for use as a systemic compound to control viral load or in the development of microbicides to prevent primary viral infection. Due to its cyanobacterial origin it is likely to show the typical drawbacks associated with pharmaceutical use of foreign proteins such as short plasma half-life, proteolysis and immunogenicity. Several strategies were used to covalently bond poly(ethylene glycol) (PEGylate) to CV-N. Random PEGylation at lysine residues resulted in poor retention of antiviral activity. Many site-directed mutants were made to test site-specific PEGylation. One mutant, where glutamine 62 was replaced with cysteine (CV-N(Q62C)) and PEGylated with maleimide activated PEG, retained significant anti-HIV activity in vitro.

Integrity signals

Registry

Crossref · 10.1016/j.addr.2007.05.016

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Nostoc produces the protein Cyanovirin, which has antiviral activities against HIV and influenza virus.
“Nostoc produce the protein Cyanovirin which have been reported for its antiviral activities against HIV an influenza virus [189].”
From The promising future of microalgae: Current status, challenges, and optimization of a sustainable and renewable industry for biofuels, feed, and other products (2018) · cites this paper as [189]

Van Damme A.
Haine, M. M.-L., & Meeùs, N. (1986) · Cited by 3,463 · see citing works
DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells
Geijtenbeek, T. B. H., Kwon, D. S., Torensma, R., van Vliet, S. J., van Duijnhoven, G. C. F., Middel, J., Cornelissen, I. L. M. H. A., Nottet, H. S. L. M., KewalRamani, V. N., Littman, D. R., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)80694-7 · Cited by 2,447 · see citing works
Chemistry for peptide and protein PEGylation
Roberts, M. J., Bentley, M. D., & Harris, J. M. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00022-4 · Cited by 1,607 · see citing works
Peptide and protein PEGylation
Veronese, F. M. (2001) · Biomaterials · doi:10.1016/s0142-9612(00)00193-9 · Cited by 1,068 · see citing works
Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells.
Leonard, C. K., Spellman, M. W., Riddle, L. M., Harris, R. J., Thomas, J. N., & Gregory, T. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)86956-3 · Cited by 986 · see citing works
Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development
Boyd, M. R., Gustafson, K. R., McMahon, J. B., Shoemaker, R. H., O’Keefe, B. R., Mori, T., Gulakowski, R. J., Wu, L., Rivera, M. I., Laurençot, C. M., et al. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.7.1521 · Cited by 606 · see citing works
HIV/AIDS in Women: An Expanding Epidemic
Quinn, T. C., & Overbaugh, J. (2005) · Science · doi:10.1126/science.1112489 · Cited by 417 · see citing works
Carbohydrates of human immunodeficiency virus. Structures of oligosaccharides linked to the envelope glycoprotein 120.
Geyer, H., Holschbach, C. S., Hunsmann, G., et al. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37849-9 · Cited by 269 · see citing works
Solution structure of cyanovirin-N, a potent HIV-inactivating protein
Bewley, C. A., Gustafson, K. R., Boyd, M. R., Covell, D. G., Bax, A., Clore, G. M., & Gronenborn, A. M. (1998) · Nature Structural Biology · doi:10.1038/828 · Cited by 265 · see citing works
The conjugation of proteins with polyethylene glycol and other polymers
Katre, N. V. (1993) · Advanced Drug Delivery Reviews · doi:10.1016/0169-409x(93)90005-o · Cited by 263 · see citing works
Involvement of macrophage mannose receptor in the binding and transmission of HIV by macrophages
Nguyen, D. G., & Hildreth, J. E. K. (2003) · European Journal of Immunology · doi:10.1002/immu.200310024 · Cited by 261 · see citing works
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
Dey, B., Lerner, D. L., Lusso, P., Boyd, M. R., Elder, J. H., & Berger, E. A. (2000) · Journal of Virology · doi:10.1128/jvi.74.10.4562-4569.2000 · Cited by 210 · see citing works
Repertoire of Chemokine Receptor Expression in the Female Genital Tract
Patterson, B. K., LANDAY, A. L., Andersson, J., Brown, C., Behbahani, H., Jiyamapa, D., Burki, Z., Stanislawski, D., Czerniewski, M. A., & Garcia, P. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65591-5 · Cited by 198 · see citing works
Potent Anti-Influenza Activity of Cyanovirin-N and Interactions with Viral Hemagglutinin
O’Keefe, B. R., Smee, D. F., Turpin, J. A., Saucedo, C. J., Gustafson, K. R., Mori, T., Blakeslee, D., Buckheit, R. W., & Boyd, M. R. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.8.2518-2525.2003 · Cited by 189 · see citing works
HIV entry inhibitors: mechanisms of action and resistance pathways
Briz, V., Poveda, E., & Soriano, V. (2006) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkl027 · Cited by 184 · see citing works
Cyanovirin-N Inhibits Hepatitis C Virus Entry by Binding to Envelope Protein Glycans
Helle, F., Wychowski, C., Vu‐Dac, N., Gustafson, K. R., Voisset, C., & Dubuisson, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602431200 · Cited by 175 · see citing works
Crystal structure of cyanovirin-N, a potent HIV-inactivating protein, shows unexpected domain swapping
Yang, F., Bewley, C. A., Louis, J. M., Gustafson, K. R., Boyd, M. R., Gronenborn, A. M., Clore, G. M., & Wlodawer, A. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2693 · Cited by 175 · see citing works
A review of vaccine research and development: The human immunodeficiency virus (HIV)☆
Girard, M. P., Osmanov, S., & Kiény, M. P. (2006) · Vaccine · doi:10.1016/j.vaccine.2006.02.031 · Cited by 174 · see citing works
Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus
Barrientos, L. G., O’Keefe, B. R., Bray, M., Sanchez, A., Gronenborn, A. M., & Boyd, M. R. (2003) · Antiviral Research · doi:10.1016/s0166-3542(02)00183-3 · Cited by 169 · see citing works
Cyanovirin-N Defines a New Class of Antiviral Agent Targeting N-Linked, High-Mannose Glycans in an Oligosaccharide-Specific Manner
Bolmstedt, A. J., O’Keefe, B. R., Shenoy, S. R., et al. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.5.949 · Cited by 150 · see citing works
Inhibition of HIV entry by carbohydrate-binding proteins
Balzarini, J. (2006) · Antiviral Research · doi:10.1016/j.antiviral.2006.02.004 · Cited by 147 · see citing works
The Potent Anti-HIV Protein Cyanovirin-N Contains Two Novel Carbohydrate Binding Sites That Selectively Bind to Man8 D1D3 and Man9 with Nanomolar Affinity: Implications for Binding to the HIV Envelope Protein gp120
Bewley, C. A., & Otero‐Quintero, S. (2001) · Journal of the American Chemical Society · doi:10.1021/ja004040e · Cited by 137 · see citing works
Emerging Drug Targets for Antiretroviral Therapy
Reeves, J. D., & Piefer, A. J. (2005) · Drugs · doi:10.2165/00003495-200565130-00002 · Cited by 137 · see citing works
Engineered Vaginal Lactobacillus Strain for Mucosal Delivery of the Human Immunodeficiency Virus Inhibitor Cyanovirin-N
Liu, X., Lagenaur, L. A., Simpson, D. A., Essenmacher, K., Frazier-Parker, C. L., Liu, Y., Tsai, D., Rao, S. S., Hamer, D. H., Parks, T., et al. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00493-06 · Cited by 136 · see citing works
The Domain-Swapped Dimer of Cyanovirin-N Is in a Metastable Folded State
Barrientos, L. G., Louis, J. M., Botos, I., Mori, T., Han, Z., O’Keefe, B. R., Boyd, M. R., Wlodawer, A., & Gronenborn, A. M. (2002) · Structure · doi:10.1016/s0969-2126(02)00758-x · Cited by 125 · see citing works
Considerations and development of topical microbicides to inhibit the sexual transmission of HIV
Turpin, J. A. (2002) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.11.8.1077 · Cited by 121 · see citing works
Profile of Resistance of Human Immunodeficiency Virus to Mannose-Specific Plant Lectins
Balzarini, J. M., Laethem, K. V., Hatse, S., et al. (2004) · Journal of Virology · doi:10.1128/jvi.78.19.10617-10627.2004 · Cited by 102 · see citing works
Isolation, Primary Sequence Determination, and Disulfide Bond Structure of Cyanovirin-N, an Anti-HIV(Human Immunodeficiency Virus) Protein from the CyanobacteriumNostoc ellipsosporum
Gustafson, K. R., Sowder, R. C., Henderson, L. E., Cardellina, J. H., McMahon, J. B., Rajamani, U., Pannell, L. K., & Boyd, M. R. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7203 · Cited by 98 · see citing works
Proteins that bind high-mannose sugars of the HIV envelope
Botos, I., & Wlodawer, A. (2004) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2004.05.001 · Cited by 94 · see citing works
Cyanovirin-N, a Potent Human Immunodeficiency Virus-Inactivating Protein, Blocks both CD4-Dependent and CD4-Independent Binding of Soluble gp120 (sgp120) to Target Cells, Inhibits sCD4-Induced Binding of sgp120 to Cell-Associated CXCR4, and Dissociates Bound sgp120 from Target Cells
Mori, T., & Boyd, M. R. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.3.664-672.2001 · Cited by 92 · see citing works
[32] Production and properties of chimeric antibody molecules
Shin, S.-U., & Morrison, S. L. (1989) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(89)78034-4 · Cited by 87 · see citing works
Transgenic plant production of Cyanovirin‐N, an HIV microbicide
Sexton, A. L., Drake, P. M. W., Mahmood, N., Harman, S. J., Shattock, R. J., & K‐C., J. (2005) · The FASEB Journal · doi:10.1096/fj.05-4742fje · Cited by 76 · see citing works
Bioengineering Lactic Acid Bacteria to Secrete the HIV-1 Virucide Cyanovirin
Pusch, O., Boden, D., Hannify, S., et al. (2005) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/01.qai.0000187446.76579.d3 · Cited by 72 · see citing works
Recombinant Production of Cyanovirin-N, a Potent Human Immunodeficiency Virus-Inactivating Protein Derived from a Cultured Cyanobacterium
Mori, T., Gustafson, K. R., Pannell, L. K., et al. (1998) · Protein Expression and Purification · doi:10.1006/prep.1997.0838 · Cited by 71 · see citing works
Development of Vaginal Microbicides for the Prevention of Heterosexual Transmission of HIV
Pauwels, R., & Clercq, E. D. (1996) · Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology · doi:10.1097/00042560-199603010-00001 · Cited by 70 · see citing works
Dissecting carbohydrate–Cyanovirin-N binding by structure-guided mutagenesis: functional implications for viral entry inhibition
Barrientos, L. G., Matei, E., Lasala, F., et al. (2006) · Protein Engineering Design and Selection · doi:10.1093/protein/gzl040 · Cited by 68 · see citing works
The microbicide cyanovirin-N expressed on the surface of commensal bacterium Streptococcus gordonii captures HIV-1
Giomarelli, B., Provvedi, R., Meacci, F., Maggi, T., Medaglini, D., Pozzi, G., Mori, T., McMahon, J. B., Gardella, R. S., & Boyd, M. R. (2002) · AIDS · doi:10.1097/00002030-200207050-00006 · Cited by 67 · see citing works
Immunology of the Vagina
Witkin, S. S. (1993) · Clinical Obstetrics & Gynecology · doi:10.1097/00003081-199303000-00017 · Cited by 37 · see citing works
Construction and Enhanced Cytotoxicity of a [Cyanovirin-N]-[PseudomonasExotoxin] Conjugate against Human Immunodeficiency Virus-Infected Cells
Mori, T., Shoemaker, R. H., McMahon, J. B., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7505 · Cited by 22 · see citing works
Parenteral Inhibitors of HIV Entry in Current Development
Lalezari, J. P., Lewis, S. T., Subramanian, G. M., Krawiec, R., Delmedico, M. K., Li, Z., Steinhauer, D. A., Klasse, P. J., & Moyle, G. J. (2006) · Cited by 2 · see citing works

Flagged first, then by citations

Sorted by citations

The promising future of microalgae: Current status, challenges, and optimization of a sustainable and renewable industry for biofuels, feed, and other products
Khan, M. I., Shin, J. H., & Kim, J. D. (2018) · Microbial Cell Factories · doi:10.1186/s12934-018-0879-x · Cited by 2,082 · see citing works
Antiviral Cyanometabolites—A Review
Mazur-Marzec, H., Cegłowska, M., Konkel, R., & Pyrć, K. (2021) · Biomolecules · doi:10.3390/biom11030474 · Cited by 64 · see citing works

The impact of PEGylation on protein immunogenicity
Gefen, T., Vaya, J., Khatib, S., Harkevich, N., Artoul, F., Heller, E. D., Pitcovski, J., & Aizenshtein, E. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2012.12.012 · Cited by 50 · see citing works
Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity
Zhang, P., Sun, F., Tsao, C., Liu, S., Jain, P. R., Sinclair, A., Hung, H., Bai, T., Wu, K., & Jiang, S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1512465112 · Cited by 316 · see citing works
Reducing the immunogenicity and improving the in vivo activity of trichosanthin by site-directed pegylation
He, X., Shaw, P., & Tam, S.-C. (1999) · Life Sciences · doi:10.1016/s0024-3205(99)00257-x · Cited by 93 · see citing works
Effect of site-directed PEGylation of trichosanthin on its biological activity, immunogenicity, and pharmacokinetics
An, Q., Lei, Y., Jia, N., et al. (2007) · Biomolecular Engineering · doi:10.1016/j.bioeng.2007.10.002 · Cited by 37 · see citing works
Precise and combinatorial PEGylation generates a low-immunogenic and stable form of human growth hormone
Wu, L., Chen, J., Wu, Y., et al. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.01.029 · Cited by 44 · see citing works

Authors: Zappe, H., Snell, M. E., & Bossard, M. J.
Affiliations: Nektar Therapeutics (United States) (US)
Hauptman-Woodward Medical Research Institute (US)
Corresponding author: Bossard, M.J.
ORCID: Snell, M.E.
Venue: Advanced Drug Delivery Reviews
Publisher: Elsevier BV
Published: 2008-01
Volume: 60
Issue: 1
Pages: 79-87
ISSN: 0169-409X (ISSN-L)
DOI: 10.1016/j.addr.2007.05.016
OpenAlex: W2092238090
Cited by: 57
References: 40
Citations by year: 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 7 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 6 · 2013: 2 · 2012: 3
FWCI: 0.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Advanced Drug Delivery Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords: cyanovirin-N, PEGylation, HIV entry inhibitors, site-specific PEGylation, site-directed mutants, antiviral activity, microbicides, protein stability, immunogenicity
MeSH terms: Amino Acid Sequence, Bacterial Proteins, Carrier Proteins, Drug Compounding, Humans, Molecular Sequence Data, Polyethylene Glycols, HIV Infections, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Anti-HIV Agents

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

PEGylation of cyanovirin–N, an entry inhibitor of HIV

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks