Carrageenan is a potent inhibitor of papillomavirus infection
Open accessAbstract
Certain sexually transmitted human papillomavirus (HPV) types are causally associated with the development of cervical cancer. Our recent development of high-titer HPV pseudoviruses has made it possible to perform high-throughput in vitro screens to identify HPV infection inhibitors. Comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted HPVs. Although carrageenan can inhibit herpes simplex viruses and some strains of HIV in vitro, genital HPVs are about a thousand-fold more susceptible, with 50% inhibitory doses in the low ng/ml range. Carrageenan acts primarily by preventing the binding of HPV virions to cells. This finding is consistent with the fact that carrageenan resembles heparan sulfate, an HPV cell-attachment factor. However, carrageenan is three orders of magnitude more potent than heparin, a form of cell-free heparan sulfate that has been regarded as a highly effective model HPV inhibitor. Carrageenan can also block HPV infection through a second, postattachment heparan sulfate-independent effect. Carrageenan is in widespread commercial use as a thickener in a variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Some of these products block HPV infectivity in vitro, even when diluted a million-fold. Clinical trials are needed to determine whether carrageenan-based products are effective as topical microbicides against genital HPVs.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Some representatives of carrageenan class demonstrate properties connected with cancer prevention, mainly due to antiviral, antioxidant properties, and stimulation of antitumor immunity.
“Some representatives of this polysaccharide class demonstrate properties connected with cancer prevention, mainly due to antiviral, antioxidant properties, and stimulation of antitumor immunity.”
From Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects (2013) · cites this paper as [93]
Carrageenan in nanomolar concentrations inhibits papillomavirus.
“Recently, it was established that carrageenan in nanomolar concentrations inhibits papillomavirus.”
From Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects (2013) · cites this paper as [93]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Contribution of Human α-Defensin 1, 2, and 3 to the Anti-HIV-1 Activity of CD8 Antiviral Factor
Zhang, L., Yu, W., Tian, H., Yu, J., Caffrey, R., Dalmasso, E. A., Fu, S., Pham, T., Mei, J., Ho, J. J., et al. (2002) · Science · doi:10.1126/science.1076185 · Cited by 468 · see citing works
RetractedClassification of papillomaviruses
de Villiers, E., Fauquet, C., Broker, T. R., Bernard, H., & Hausen, H. Z. (2004) · Virology · doi:10.1016/j.virol.2004.03.033 · Cited by 3,192 · see citing works
Order Out of Chaos: Assembly of Ligand Binding Sites in Heparan Sulfate
Esko, J. D., & Selleck, S. B. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135458 · Cited by 1,495 · see citing works
Epidemiology of Genital Human Papillomavirus Infection
Koutsky, L. A. (1997) · The American Journal of Medicine · doi:10.1016/s0002-9343(97)00177-0 · Cited by 1,121 · see citing works
Antimicrobial peptides: premises and promises
Reddy, K. V. R., Yedery, R. D., & Aranha, C. C. (2004) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2004.09.005 · Cited by 1,072 · see citing works
Doorbar, J. (2005) · Journal of Clinical Virology · doi:10.1016/j.jcv.2004.12.006 · Cited by 856 · see citing works
Effectiveness of condoms in preventing sexually transmitted infections.
(2004) · Europe PMC (PubMed Central) · Cited by 655 · see citing works
Animal cell mutants defective in glycosaminoglycan biosynthesis.
Esko, J. D., Stewart, T., & Taylor, W. H. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.10.3197 · Cited by 608 · see citing works
Human Papillomavirus Infection Requires Cell Surface Heparan Sulfate
Giroglou, T., Florin, L., Schäfer, F., Streeck, R. E., & Sapp, M. J. (2001) · Journal of Virology · doi:10.1128/jvi.75.3.1565-1570.2001 · Cited by 574 · see citing works
The carcinogenicity of human papillomavirus types reflects viral evolution
SCHIFFMAN, M. H., Herrero, R., DeSalle, R., Hildesheim, A., Wacholder, S., Rodríguez, A. C., Bratti, M. C., Sherman, M. E., Morales, J., Guillén, D., et al. (2005) · Virology · doi:10.1016/j.virol.2005.04.002 · Cited by 555 · see citing works
Baba, M., Snoeck, R., Pauwels, R., & Clercq, E. D. (1988) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.32.11.1742 · Cited by 545 · see citing works
Sulfated Polysaccharides Extracted from Sea Algae as Potential Antiviral Drugs
Witvrouw, M., & Clercq, E. D. (1997) · General Pharmacology The Vascular System · doi:10.1016/s0306-3623(96)00563-0 · Cited by 531 · see citing works
Chapter 2: Natural History of Anogenital Human Papillomavirus Infection and Neoplasia
SCHIFFMAN, M. H., & Kjær, S. K. (2003) · JNCI Monographs · doi:10.1093/oxfordjournals.jncimonographs.a003476 · Cited by 512 · see citing works
Efficient Intracellular Assembly of Papillomaviral Vectors
Buck, C. B., Pastrana, D. V., Lowy, D. R., & Schiller, J. T. (2003) · Journal of Virology · doi:10.1128/jvi.78.2.751-757.2004 · Cited by 489 · see citing works
Self-citationEfficacy of Human Papillomavirus-16 Vaccine to Prevent Cervical Intraepithelial Neoplasia
Mao, C., Koutsky, L. A., Ault, K. A., et al. (2006) · Obstetrics and Gynecology · doi:10.1097/01.aog.0000192397.41191.fb · Cited by 452 · see citing works
Joyce, J. G., Tung, J., Przysiecki, C. T., Cook, J. C., Lehman, E. D., Sands, J. A., Jansen, K. U., & Keller, P. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.9.5810 · Cited by 429 · see citing works
Do Condoms Prevent Genital HPV Infection, External Genital Warts, or Cervical Neoplasia?
Manhart, L. E., & Koutsky, L. A. (2002) · Sexually Transmitted Diseases · doi:10.1097/00007435-200211000-00018 · Cited by 396 · see citing works
Review of harmful gastrointestinal effects of carrageenan in animal experiments.
Tobacman, J. K. (2001) · Environmental Health Perspectives · doi:10.1289/ehp.01109983 · Cited by 370 · see citing works
Pastrana, D. V., Buck, C. B., Pang, Y.-Y. S., Thompson, C. D., Castle, P. E., FitzGerald, P. C., Kjær, S. K., Lowy, D. R., & Schiller, J. T. (2004) · Virology · doi:10.1016/j.virol.2003.12.027 · Cited by 358 · see citing works
Self-citationA quantitative in vitro focus assay for bovine papilloma virus
Dvoretzky, I., Shober, R., Chattopadhyay, S. K., et al. (1980) · Virology · doi:10.1016/0042-6822(80)90195-6 · Cited by 309 · see citing works
Moulard, M., Lortat‐Jacob, H., Mondor, I., Roca, G., Wyatt, R. T., Sodroski, J., Zhao, L., Olson, W. C., Kwong, P. D., & Sattentau, Q. J. (2000) · Journal of Virology · doi:10.1128/jvi.74.4.1948-1960.2000 · Cited by 297 · see citing works
Maturation of Papillomavirus Capsids
Buck, C. B., Thompson, C. D., Pang, Y.-Y. S., Lowy, D. R., & Schiller, J. T. (2005) · Journal of Virology · doi:10.1128/jvi.79.5.2839-2846.2005 · Cited by 289 · see citing works
Self-citationTalarico, L. B., Pujol, C. A., ZIBETTI, R., de Faria, P. A. C., Noseda, M. D., Duarte, M. E. R., & Damonte, E. B. (2005) · Antiviral Research · doi:10.1016/j.antiviral.2005.02.001 · Cited by 277 · see citing works
Human α-defensins block papillomavirus infection
Buck, C. B., Day, P. M., Thompson, C. D., Lubkowski, J. T., Lu, W., Lowy, D. R., & Schiller, J. T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508033103 · Cited by 238 · see citing works
Self-citationPolysaccharides as antiviral agents: antiviral activity of carrageenan
González, M. E., Alarcón, B., & Carrasco, L. (1987) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.31.9.1388 · Cited by 187 · see citing works
Pastrana, D. V., Gambhira, R., Buck, C. B., Pang, Y.-Y. S., Thompson, C. D., Culp, T. D., Christensen, N. D., Lowy, D. R., Schiller, J. T., & Roden, R. B. S. (2005) · Virology · doi:10.1016/j.virol.2005.04.011 · Cited by 186 · see citing works
Self-citationHuman Papillomavirus Types 16, 31, and 58 Use Different Endocytosis Pathways To Enter Cells
Bousarghin, L., Touzé, A., Sizaret, P.-Y., & Coursaget, P. (2003) · Journal of Virology · doi:10.1128/jvi.77.6.3846-3850.2003 · Cited by 171 · see citing works
Postnatal Descent of the Epiglottis in Man: A Preliminary Report
Sasaki, C. T., Levine, P. A., Laitman, J. T., et al. (1977) · Archives of Otolaryngology - Head and Neck Surgery · doi:10.1001/archotol.1977.00780200095011 · Cited by 171 · see citing works
ERp29 Triggers a Conformational Change in Polyomavirus to Stimulate Membrane Binding
Magnuson, B., Rainey-Barger, E. K., Benjamin, T. L., Baryshev, M., Mkrtchian, S., & Tsai, B. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.08.034 · Cited by 161 · see citing works
Stabilization of human papillomavirus virus-like particles by non-ionic surfactants
Shi, L., Sanyal, G., Ni, A., et al. (2005) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20377 · Cited by 126 · see citing works
Intercapsomeric Disulfide Bonds in Papillomavirus Assembly and Disassembly
Li, M., Beard, P., Estes, P. A., et al. (1998) · Journal of Virology · doi:10.1128/jvi.72.3.2160-2167.1998 · Cited by 122 · see citing works
Further Evidence that Papillomavirus Capsids Exist inTwo DistinctConformations
Selinka, H., Giroglou, T., Nowak, T., et al. (2003) · Journal of Virology · doi:10.1128/jvi.77.24.12961-12967.2003 · Cited by 121 · see citing works
Vaginal formulations of carrageenan protect mice from herpes simplex virus infection
Zacharopoulos, V. R., & Phillips, D. M. (1997) · Clinical and Diagnostic Laboratory Immunology · doi:10.1128/cdli.4.4.465-468.1997 · Cited by 120 · see citing works
NHPV16 VLP Vaccine Induces Human Antibodies That Neutralize Divergent Variants of HPV16
Pastrana, D. V., Vass, W. C., Lowy, D. R., et al. (2001) · Virology · doi:10.1006/viro.2000.0702 · Cited by 112 · see citing works
Self-citationA Broad-Spectrum Microbicide with Virucidal Activity against Sexually Transmitted Viruses
Howett, M. K., Neely, E. B., Christensen, N. D., Wigdahl, B. L., Krebs, F. C., Malamud, D., Patrick, S. D., Pickel, M. D., Welsh, P. A., Reed, C. A., et al. (1999) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.43.2.314 · Cited by 109 · see citing works
Zhang, Y., Hatziioannou, T., Zang, T. M., Braaten, D. C., Luban, J., Goff, S. P., & Bieniasz, P. D. (2002) · Journal of Virology · doi:10.1128/jvi.76.12.6332-6343.2002 · Cited by 108 · see citing works
Culp, T. D., Budgeon, L. R., & Christensen, N. D. (2005) · Virology · doi:10.1016/j.virol.2005.11.025 · Cited by 101 · see citing works
Christensen, N. D., Reed, C. A., Culp, T. D., et al. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.12.3427-3432.2001 · Cited by 101 · see citing works
Preliminary safety and acceptability of a carrageenan gel for possible use as a vaginal microbicide
Coggins, C. (2000) · Sexually Transmitted Infections · doi:10.1136/sti.76.6.480 · Cited by 101 · see citing works
Lactoferrin inhibits human papillomavirus binding and uptake in vitro
Drobni, P., Näslund, J., & Evander, M. (2004) · Antiviral Research · doi:10.1016/j.antiviral.2004.05.005 · Cited by 97 · see citing works
Tests of vaginal microbicides in the mouse genital herpes model
Zeitlin, L., Whaley, K. J., Hegarty, T. A., Moench, T. R., & Cone, R. A. (1997) · Contraception · doi:10.1016/s0010-7824(97)00154-6 · Cited by 88 · see citing works
Glomb-Reinmund, S., & Kielian, M. C. (1998) · Virology · doi:10.1006/viro.1998.9275 · Cited by 85 · see citing works
Inhibitory Effect of Tachyplesin I on the Proliferation of Human Immunodeficiency Virus in vitro
Morimoto, M., Mori, H., Otake, T., et al. (2009) · Chemotherapy · doi:10.1159/000238855 · Cited by 75 · see citing works
Recurrent respiratory papillomatosis: pathogenesis to treatment
Lee, J. H., & Smith, R. J. (2005) · Current Opinion in Otolaryngology & Head & Neck Surgery · doi:10.1097/01.moo.0000186205.91332.46 · Cited by 72 · see citing works
Human Papillomavirus Type 31b Infection of Human Keratinocytes Does Not Require Heparan Sulfate
Patterson, N. A., Smith, J. L., & Ozbun, M. A. (2005) · Journal of Virology · doi:10.1128/jvi.79.11.6838-6847.2005 · Cited by 68 · see citing works
Baghian, A., Jaynes, J. M., Enright, F. M., et al. (1997) · Peptides · doi:10.1016/s0196-9781(96)00290-2 · Cited by 62 · see citing works
Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan
Elias, C. J., Coggins, C., Alvarez, F., et al. (1997) · Contraception · doi:10.1016/s0010-7824(97)00176-5 · Cited by 62 · see citing works
Antioxidant Defenses Influence HIV-1 Replication and Associated Cytopathic Effects
Sandstrom, P. A., Murray, J. L., Folks, T. M., & Diamond, A. M. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00023-9 · Cited by 61 · see citing works
Protein disulfide isomerase suppresses the transcriptional activity of NF-κB
Higuchi, T., Watanabe, Y., & Waga, I. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.04.002 · Cited by 59 · see citing works
Microbicides for Prevention of Transmission of Sexually Transmitted Diseases
Howett, M. K., & Kuhl, J. (2005) · Current Pharmaceutical Design · doi:10.2174/138161205774580633 · Cited by 48 · see citing works
Lynch, G. W., Low, L., LI, S., et al. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.56.3.266 · Cited by 45 · see citing works
Doncel, G. F. (2005) · Human Reproduction Update · doi:10.1093/humupd/dmi040 · Cited by 43 · see citing works
Bourinbaiar, A. S., & Coleman, C. F. (1997) · Archives of Virology · doi:10.1007/s007050050237 · Cited by 37 · see citing works
The Spermicide Nonoxynol-9 Does Not Inactivate Papillomavirus
Hermonat, P. L., Daniel, R. W., & Shah, K. V. (1992) · Sexually Transmitted Diseases · doi:10.1097/00007435-199207000-00004 · Cited by 29 · see citing works
Preclinical evaluation of magainin-A as a contraceptive antimicrobial agent
Clara, A., Manjramkar, D. D., & Reddy, V. R. K. (2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.09.073 · Cited by 27 · see citing works
Ishikawa, A., Kubota, Y., Murayama, T., et al. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00850-2 · Cited by 25 · see citing works
Effect of polyanion-resistance on HIV-1 infection
Bobardt, M. D., Armand‐Ugón, M., Clotet, I., et al. (2004) · Virology · doi:10.1016/j.virol.2004.05.011 · Cited by 23 · see citing works
Delivering Reassurance to Parents: Perinatal Human Papillomavirus Transmission Is Rare
Winer, R. L., & Koutsky, L. A. (2004) · Sexually Transmitted Diseases · doi:10.1097/01.olq.0000108768.62279.66 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Bioactive compounds in seaweed: functional food applications and legislation
Holdt, S. L., & Kraan, S. (2011) · Journal of Applied Phycology · doi:10.1007/s10811-010-9632-5 · Cited by 2,135 · see citing works
Nutraceutical Potential of Seaweed Polysaccharides: Structure, Bioactivity, Safety, and Toxicity
Tanna, B., & Mishra, A. (2019) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12441 · Cited by 329 · see citing works
Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects
Fedorov, S., Ermakova, S., Zvyagintseva, T., & Stonik, V. (2013) · Marine Drugs · doi:10.3390/md11124876 · Cited by 189 · see citing works
Algae-derived bioactive molecules for the potential treatment of SARS-CoV-2
Alam, M. A., Parra-Saldivar, R., Bilal, M., Afroze, C. A., Ahmed, M. N., Iqbal, H. M. N., & Xu, J. (2021) · Molecules · doi:10.3390/molecules26082134 · Cited by 69 · see citing works
Omics for Bioprospecting and Drug Discovery from Bacteria and Microalgae
Maghembe, R., Damian, D., Makaranga, A., Nyandoro, S. S., Lyantagaye, S. L., Kusari, S., & Hatti-Kaul, R. (2020) · Antibiotics · doi:10.3390/antibiotics9050229 · Cited by 66 · see citing works
An Overview of Phycocolloids: The Principal Commercial Seaweed Extracts
Pangestuti, R., & Kim, S. (2015) · Marine Algae Extracts · doi:10.1002/9783527679577.ch19 · Cited by 25 · see citing works
- Authors
- Buck, C. B., Thompson, C. D., Roberts, J. N., Müller, M., Lowy, D. R., & Schiller, J. T.
- Affiliations
- National Cancer Institute (US)
- National Institutes of Health (US)
- German Cancer Research Center (DE)
- Corresponding author
- Schiller, John T
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2006-07-14
- Volume
- 2
- Issue
- 7
- Pages
- e69
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC1500806
- OpenAlex
- W2125372939
- Cited by
- 497
- References
- 58
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 26 · 2023: 32 · 2022: 41 · 2021: 44 · 2020: 47 · 2019: 20 · 2018: 25 · 2017: 19 · 2016: 14 · 2015: 32 · 2014: 25 · 2013: 25 · 2012: 25
- FWCI
- 11.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Health Sciences › Medicine › Surgery › Genital Health and Disease
- Keywords
- carrageenan, human papillomavirus, heparan sulfate, heparin, sulfated polysaccharides, microbicides, cervical cancer, sexually transmitted infections, topical antiviral agents, food additives
- MeSH terms
- Administration, Topical, Animals, Anti-Infective Agents, Local, Capsid, Carrageenan, Cell Line, Dose-Response Relationship, Drug, Female, Cricetinae, HeLa Cells, Heparin, Heparitin Sulfate, Heparan Sulfate, Humans, Hydrogen-Ion Concentration, Polysaccharides, Virion, Sexually Transmitted Diseases, Viral, CHO Cells, Papillomaviridae, Papillomavirus Infections, Mice
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
