{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:33:27Z","timestamp":1791362007807,"version":"4.3.1"},"reference-count":124,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T00:00:00Z","timestamp":1597968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1F1A1058628"],"award-info":[{"award-number":["NRF-2019R1F1A1058628"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Different kinds of red algae are enriched with chemically diverse carbohydrates. In particular, a group of sulfated polysaccharides, which were isolated from the cell walls of red algae, gained a large amount of attention due to their broad-spectrum antimicrobial activities. Within that group, carrageenans (CGs) were expected to be the first clinically applicable microbicides that could prevent various viral infections due to their superior antiviral potency and desirable safety profiles in subclinical studies. However, their anticipated beneficial effects could not be validated in human studies. To assess the value of a second attempt at pharmacologically developing CGs as a new class of preventive microbicides, all preclinical and clinical development processes of CG-based microbicides need to be thoroughly re-evaluated. In this review, the in vitro toxicities; in vivo safety profiles; and in vitro, ex vivo, and in vivo antiviral activities of CGs are summarized according to the study volume of their target viruses, which include human immunodeficiency virus, herpesviruses, respiratory viruses, human papillomavirus, dengue virus, and other viruses along with a description of their antiviral modes of action and development of antiviral resistance. This evaluation of the strengths and weaknesses of CGs will help provide future research directions that may lead to the successful development of CG-based antimicrobial prophylactics.<\/jats:p>","DOI":"10.3390\/md18090435","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T09:21:51Z","timestamp":1598001711000},"page":"435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Carrageenans as Broad-Spectrum Microbicides: Current Status and Challenges"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-8428","authenticated-orcid":false,"given":"Choongho","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy, Dongguk University, Goyang 10326, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"825203","DOI":"10.1155\/2015\/825203","article-title":"Antiviral Potential of Algae Polysaccharides Isolated from Marine Sources: A Review","volume":"2015","author":"Ahmadi","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.2174\/0929867043364504","article-title":"Sulfated seaweed polysaccharides as antiviral agents","volume":"11","author":"Damonte","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0306-3623(96)00563-0","article-title":"Sulfated polysaccharides extracted from sea algae as potential antiviral drugs","volume":"29","author":"Witvrouw","year":"1997","journal-title":"Gen. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.antiviral.2011.03.176","article-title":"The rise and fall of polyanionic inhibitors of the human immunodeficiency virus type 1","volume":"90","author":"Pirrone","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1289\/ehp.01109983","article-title":"Review of harmful gastrointestinal effects of carrageenan in animal experiments","volume":"109","author":"Tobacman","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1097\/QAD.0b013e3282ef83fd","article-title":"Vaginal microbicides: Moving ahead after an unexpected setback","volume":"21","author":"Shattock","year":"2007","journal-title":"AIDS"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1128\/AAC.02468-15","article-title":"Multipurpose Prevention Approaches with Antiretroviral-Based Formulations","volume":"60","author":"Barnable","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1128\/AAC.00796-13","article-title":"A modified zinc acetate gel, a potential nonantiretroviral microbicide, is safe and effective against simian-human immunodeficiency virus and herpes simplex virus 2 infection in vivo","volume":"57","author":"Kenney","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1128\/AAC.00392-16","article-title":"In Vitro Exposure to PC-1005 and Cervicovaginal Lavage Fluid from Women Vaginally Administered PC-1005 Inhibits HIV-1 and HSV-2 Infection in Human Cervical Mucosa","volume":"60","author":"Villegas","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1016\/j.antiviral.2013.09.030","article-title":"Multipurpose prevention technologies: Products in development","volume":"100","author":"Friend","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/S0140-6736(08)61842-5","article-title":"Efficacy of Carraguard for prevention of HIV infection in women in South Africa: A randomised, double-blind, placebo-controlled trial","volume":"372","author":"Ramjee","year":"2008","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Turville, S.G., Aravantinou, M., Miller, T., Kenney, J., Teitelbaum, A., Hu, L., Chudolij, A., Zydowsky, T.M., Piatak, M., and Bess, J.W. (2008). Efficacy of Carraguard-based microbicides in vivo despite variable in vitro activity. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003162"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1743-422X-9-33","article-title":"Application and removal of polyanionic microbicide compounds enhances subsequent infection by HIV-1","volume":"9","author":"Pirrone","year":"2012","journal-title":"Virol. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tan, S., Lu, L., Li, L., Liu, J., Oksov, Y., Lu, H., Jiang, S., and Liu, S. (2013). Polyanionic candidate microbicides accelerate the formation of semen-derived amyloid fibrils to enhance HIV-1 infection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059777"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1089\/aid.2008.0043","article-title":"Enhancement of HIV infection by cellulose sulfate","volume":"24","author":"Tao","year":"2008","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.virusres.2014.02.011","article-title":"Changes in antiviral susceptibility to entry inhibitors and endocytic uptake of dengue-2 virus serially passaged in Vero or C6\/36 cells","volume":"184","author":"Acosta","year":"2014","journal-title":"Virus Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0166-3542(90)90009-V","article-title":"Inhibitory effect of selected antiviral compounds on arenavirus replication in vitro","volume":"14","author":"Andrei","year":"1990","journal-title":"Antivir. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1128\/AAC.32.11.1742","article-title":"Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus, and human immunodeficiency virus","volume":"32","author":"Baba","year":"1988","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.antiviral.2003.09.005","article-title":"In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: Synergistic effect of interferon-alpha and ribavirin combination","volume":"61","author":"Briolant","year":"2004","journal-title":"Antivir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Buck, C.B., Thompson, C.D., Roberts, J.N., Muller, M., Lowy, D.R., and Schiller, J.T. (2006). Carrageenan is a potent inhibitor of papillomavirus infection. PLoS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020069"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0031-9422(99)00461-6","article-title":"Carrageenans from chilean samples of Stenogramme interrupta (Phyllophoraceae): Structural analysis and biological activity","volume":"53","author":"Caceres","year":"2000","journal-title":"Phytochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0166-3542(99)00038-8","article-title":"Antiherpetic activity and mode of action of natural carrageenans of diverse structural types","volume":"43","author":"Carlucci","year":"1999","journal-title":"Antivir. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0141-8130(96)01145-2","article-title":"Antiherpetic and anticoagulant properties of carrageenans from the red seaweed Gigartina skottsbergii and their cyclized derivatives: Correlation between structure and biological activity","volume":"20","author":"Carlucci","year":"1997","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1159\/000007236","article-title":"Inhibitory action of natural carrageenans on Herpes simplex virus infection of mouse astrocytes","volume":"45","author":"Carlucci","year":"1999","journal-title":"Chemotherapy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.carbpol.2015.04.030","article-title":"Partial and total C-6 oxidation of gelling carrageenans. Modulation of the antiviral activity with the anionic character","volume":"128","author":"Cosenza","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.rvsc.2014.11.010","article-title":"Antiviral activity of lambda-carrageenan prepared from red seaweed (Gigartina skottsbergii) against BoHV-1 and SuHV-1","volume":"98","author":"Diogo","year":"2015","journal-title":"Res. Vet. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0166-3542(91)90031-L","article-title":"Antiviral activity of sulfated polysaccharides against African swine fever virus","volume":"15","year":"1991","journal-title":"Antivir. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0923-2516(91)90011-Q","article-title":"Antiviral activity of carrageenan on hepatitis A virus replication in cell culture","volume":"142","author":"Girond","year":"1991","journal-title":"Res. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"024110","DOI":"10.1063\/1.4870772","article-title":"Assessment of the inhibition of Dengue virus infection by carrageenan via real-time monitoring of cellular oxygen consumption rates within a microfluidic device","volume":"8","author":"Huang","year":"2014","journal-title":"Biomicrofluidics"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Luo, Z., Tian, D., Zhou, M., Xiao, W., Zhang, Y., Li, M., Sui, B., Wang, W., Guan, H., and Chen, H. (2015). lambda-Carrageenan P32 Is a Potent Inhibitor of Rabies Virus Infection. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140586"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1179\/joc.1995.7.2.90","article-title":"Inhibition of herpes simplex virus infection by negatively charged and neutral carbohydrate polymers","volume":"7","author":"Marchetti","year":"1995","journal-title":"J. Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Penuela, A., Robledo, D., Bourgougnon, N., Bedoux, G., Hernandez-Nunez, E., and Freile-Pelegrin, Y. (2018). Environmentally Friendly Valorization of Solieria filiformis (Gigartinales, Rhodophyta) from IMTA Using a Biorefinery Concept. Mar. Drugs, 16.","DOI":"10.3390\/md16120487"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.antiviral.2014.05.018","article-title":"In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition","volume":"108","author":"Rodriguez","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shao, Q., Guo, Q., Xu, W., Li, Z., and Zhao, T. (2015). Specific Inhibitory Effect of kappa-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126577"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1128\/AAC.29.2.284","article-title":"New agents active against African swine fever virus","volume":"29","author":"Sola","year":"1986","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.virol.2007.01.043","article-title":"Interference in dengue virus adsorption and uncoating by carrageenans","volume":"363","author":"Talarico","year":"2007","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1002\/jmv.24457","article-title":"Characterization of in vitro dengue virus resistance to carrageenan","volume":"88","author":"Talarico","year":"2016","journal-title":"J. Med. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1099\/vir.0.028522-0","article-title":"Differential inhibition of dengue virus infection in mammalian and mosquito cells by iota-carrageenan","volume":"92","author":"Talarico","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.antiviral.2005.02.001","article-title":"The antiviral activity of sulfated polysaccharides against dengue virus is dependent on virus serotype and host cell","volume":"66","author":"Talarico","year":"2005","journal-title":"Antivir. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ijbiomac.2004.03.002","article-title":"Anti-herpes simplex virus activity of sulfated galactans from the red seaweeds Gymnogongrus griffithsiae and Cryptonemia crenulata","volume":"34","author":"Talarico","year":"2004","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1021\/jm010969d","article-title":"Synthesis of new covalently bound kappa-carrageenan-AZT conjugates with improved anti-HIV activities","volume":"45","author":"Vlieghe","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.antiviral.2011.08.010","article-title":"In vitro inhibitory effect of carrageenan oligosaccharide on influenza A H1N1 virus","volume":"92","author":"Wang","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1080\/15384101.2019.1691363","article-title":"Antiviral bioactivity of renewable polysaccharides against Varicella Zoster","volume":"18","author":"Huleihel","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0010-7824(97)00176-5","article-title":"Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan","volume":"56","author":"Elias","year":"1997","journal-title":"Contraception"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1097\/OLQ.0b013e31815d6e0d","article-title":"A randomized, placebo-controlled trial to assess the safety and acceptability of use of carraguard vaginal gel by heterosexual couples in Thailand","volume":"35","author":"Kilmarx","year":"2008","journal-title":"Sex. Transm. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1097\/QAI.0b013e318159d5a8","article-title":"Carraguard Vaginal Gel Safety in HIV-Positive Women and Men in South Africa","volume":"46","author":"Braunstein","year":"2007","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1097\/QAI.0b013e31815d2f12","article-title":"No increase in cervicovaginal proinflammatory cytokines after Carraguard use in a placebo-controlled randomized clinical trial","volume":"47","author":"Bollen","year":"2008","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1097\/QAD.0b013e32801086c9","article-title":"Acceptability of Carraguard vaginal gel use among Thai couples","volume":"20","author":"Whitehead","year":"2006","journal-title":"AIDS"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1097\/QAI.0000000000001136","article-title":"First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics","volume":"73","author":"Friedland","year":"2016","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1097\/QAD.0b013e328333bf89","article-title":"HIV genital shedding and safety of Carraguard use by HIV-infected women: A crossover trial in Thailand","volume":"24","author":"McLean","year":"2010","journal-title":"AIDS"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1097\/01.qai.0000243056.59860.c1","article-title":"Safety and acceptability of the candidate microbicide Carraguard in Thai Women: Findings from a Phase II Clinical Trial","volume":"43","author":"Kilmarx","year":"2006","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1742-6405-4-20","article-title":"Acceptability of Carraguard, a candidate microbicide and methyl cellulose placebo vaginal gels among HIV-positive women and men in Durban, South Africa","volume":"4","author":"Ramjee","year":"2007","journal-title":"AIDS Res. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Carraguard Phase II South Africa Study Team (2010). Expanded safety and acceptability of the candidate vaginal microbicide Carraguard(R) in South Africa. Contraception, 82, 563\u2013571.","DOI":"10.1016\/j.contraception.2010.04.019"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Whitehead, S.J., McLean, C., Chaikummao, S., Braunstein, S., Utaivoravit, W., van de Wijgert, J.H., Mock, P.A., Siraprapasiri, T., Friedland, B.A., and Kilmarx, P.H. (2011). Acceptability of Carraguard vaginal microbicide gel among HIV-infected women in Chiang Rai, Thailand. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014831"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1095\/biolreprod54.1.173","article-title":"Sulfated polysaccharides inhibit lymphocyte-to-epithelial transmission of human immunodeficiency virus-1","volume":"54","author":"Phillips","year":"1996","journal-title":"Biol. Reprod."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/jlb.56.3.266","article-title":"Sulfated polyanions prevent HIV infection of lymphocytes by disruption of the CD4-gp120 interaction, but do not inhibit monocyte infection","volume":"56","author":"Lynch","year":"1994","journal-title":"J. Leukoc. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1006\/eesa.1999.1862","article-title":"Anti-HIV activity of extracts and compounds from algae and cyanobacteria","volume":"45","author":"Schaeffer","year":"2000","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/glycob\/cwn092","article-title":"Focus on antivirally active sulfated polysaccharides: From structure-activity analysis to clinical evaluation","volume":"19","author":"Ghosh","year":"2009","journal-title":"Glycobiology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.3390\/md10122795","article-title":"The antiviral activities and mechanisms of marine polysaccharides: An overview","volume":"10","author":"Wang","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.copbio.2010.02.008","article-title":"Red microalgal cell-wall polysaccharides: Biotechnological aspects","volume":"21","author":"Arad","year":"2010","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1128\/AAC.31.10.1524","article-title":"Purification and characterization of an avian myeloblastosis and human immunodeficiency virus reverse transcriptase inhibitor, sulfated polysaccharides extracted from sea algae","volume":"31","author":"Nakashima","year":"1987","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1099\/0022-1317-75-1-111","article-title":"Inhibition by iota-carrageenan of the spread of murine cytomegalovirus from the peritoneal cavity to the blood plasma","volume":"75","author":"Hamasuna","year":"1994","journal-title":"J. Gen. Virol."},{"key":"ref_63","first-page":"353","article-title":"Protective effect of carrageenan against murine cytomegalovirus infection in mice","volume":"4","author":"Hamasuna","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1126\/science.1193748","article-title":"Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women","volume":"329","author":"Frohlich","year":"2010","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Berry, M., Wirtz, A.L., Janayeva, A., Ragoza, V., Terlikbayeva, A., Amirov, B., Baral, S., and Beyrer, C. (2012). Risk factors for HIV and unprotected anal intercourse among men who have sex with men (MSM) in Almaty, Kazakhstan. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043071"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0144-8617(96)00128-2","article-title":"Preparation and anti-HIV activity of low molecular-weight carrageenans and their sulfated derivatives","volume":"32","author":"Yamada","year":"1997","journal-title":"Carbohydr. Polym."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/01.olq.0000223287.46097.4b","article-title":"Carrageenan\/MIV-150 (PC-815), a combination microbicide","volume":"34","author":"Thorn","year":"2007","journal-title":"Sex. Transm. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1159\/000322355","article-title":"Mucosal human defensins 5 and 6 antagonize the anti-HIV activity of candidate polyanion microbicides","volume":"3","author":"Ding","year":"2011","journal-title":"J. Innate Immun."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Barnable, P., Calenda, G., Ouattara, L., Gettie, A., Blanchard, J., Jean-Pierre, N., Kizima, L., Rodriguez, A., Abraham, C., and Menon, R. (2014). A MIV-150\/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108109"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1128\/AAC.00073-15","article-title":"MIV-150\/zinc acetate gel inhibits cell-associated simian-human immunodeficiency virus reverse transcriptase infection in a macaque vaginal explant model","volume":"59","author":"Barnable","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1128\/AAC.01129-06","article-title":"Preclinical testing of candidate topical microbicides for anti-human immunodeficiency virus type 1 activity and tissue toxicity in a human cervical explant culture","volume":"51","author":"Cummins","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1095\/biolreprod.102.014555","article-title":"Carrageenan formulation prevents macrophage trafficking from vagina: Implications for microbicide development","volume":"69","author":"Perotti","year":"2003","journal-title":"Biol. Reprod."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kenney, J., Aravantinou, M., Singer, R., Hsu, M., Rodriguez, A., Kizima, L., Abraham, C.J., Menon, R., Seidor, S., and Chudolij, A. (2011). An antiretroviral\/zinc combination gel provides 24 hours of complete protection against vaginal SHIV infection in macaques. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0015835"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5504","DOI":"10.1128\/JVI.02422-10","article-title":"The nonnucleoside reverse transcriptase inhibitor MIV-150 in carrageenan gel prevents rectal transmission of simian\/human immunodeficiency virus infection in macaques","volume":"85","author":"Singer","year":"2011","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1089\/aid.2012.0087","article-title":"A single dose of a MIV-150\/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8\u201324 h after gel use","volume":"28","author":"Kenney","year":"2012","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Halpern, V., Ogunsola, F., Obunge, O., Wang, C.H., Onyejepu, N., Oduyebo, O., Taylor, D., McNeil, L., Mehta, N., and Umo-Otong, J. (2008). Effectiveness of cellulose sulfate vaginal gel for the prevention of HIV infection: Results of a Phase III trial in Nigeria. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003784"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1056\/NEJMoa0707957","article-title":"Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission","volume":"359","author":"Govinden","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1128\/JVI.01366-08","article-title":"The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection","volume":"83","author":"Roan","year":"2009","journal-title":"J. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.cell.2007.10.014","article-title":"Semen-derived amyloid fibrils drastically enhance HIV infection","volume":"131","author":"Munch","year":"2007","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1038\/s41467-018-06349-0","article-title":"Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo","volume":"9","author":"Derby","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0010-7824(97)00154-6","article-title":"Tests of vaginal microbicides in the mouse genital herpes model","volume":"56","author":"Zeitlin","year":"1997","journal-title":"Contraception"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0166-3542(99)00020-0","article-title":"Plant products as topical microbicide candidates: Assessment of in vitro and in vivo activity against herpes simplex virus type 2","volume":"42","author":"Bourne","year":"1999","journal-title":"Antivir. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/0006-291X(87)90791-1","article-title":"Animal viruses promote the entry of polysaccharides with antiviral activity into cells","volume":"146","author":"Gonzalez","year":"1987","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.antiviral.2004.07.001","article-title":"Protective effect of a natural carrageenan on genital herpes simplex virus infection in mice","volume":"64","author":"Carlucci","year":"2004","journal-title":"Antivir. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1128\/AAC.05461-11","article-title":"Zinc acetate\/carrageenan gels exhibit potent activity in vivo against high-dose herpes simplex virus 2 vaginal and rectal challenge","volume":"56","author":"Abraham","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7290","DOI":"10.1128\/AAC.01816-15","article-title":"Griffithsin and Carrageenan Combination To Target Herpes Simplex Virus 2 and Human Papillomavirus","volume":"59","author":"Levendosky","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00007435-200105000-00003","article-title":"Comparison of microbicides for efficacy in protecting mice against vaginal challenge with herpes simplex virus type 2, cytotoxicity, antibacterial properties, and sperm immobilization","volume":"28","author":"Maguire","year":"2001","journal-title":"Sex. Transm. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1167\/iovs.07-1245","article-title":"Effects of lambda-carrageenan on in vitro replication of feline herpesvirus and on experimentally induced herpetic conjunctivitis in cats","volume":"49","author":"Stiles","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1128\/cdli.4.4.465-468.1997","article-title":"Vaginal formulations of carrageenan protect mice from herpes simplex virus infection","volume":"4","author":"Zacharopoulos","year":"1997","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1097\/00007435-199810000-00010","article-title":"Carrageenan-based nonoxynol-9 spermicides for prevention of sexually transmitted infections","volume":"25","author":"Maguire","year":"1998","journal-title":"Sex. Transm. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/jmv.10174","article-title":"Herpes simplex virus type 1 variants arising after selection with an antiviral carrageenan: Lack of correlation between drug susceptibility and syn phenotype","volume":"68","author":"Carlucci","year":"2002","journal-title":"J. Med. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1097\/OLQ.0b013e3182084d99","article-title":"Emergence of Herpes Simplex Virus-1 Syncytial Variants With Altered Virulence for Mice After Selection With a Natural Carrageenan","volume":"38","author":"Mateu","year":"2011","journal-title":"Sex. Transm. Dis."},{"key":"ref_93","first-page":"68","article-title":"Altered expression of cytokines in mice infected intranasally with two syncytial variants of Herpes simplex virus type 1","volume":"71","author":"Linero","year":"2014","journal-title":"Microb. Pathog."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"275","DOI":"10.2147\/IJGM.S167123","article-title":"Development of a nasal spray containing xylometazoline hydrochloride and iota-carrageenan for the symptomatic relief of nasal congestion caused by rhinitis and sinusitis","volume":"11","author":"Graf","year":"2018","journal-title":"Int. J. Gen. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/1743-422X-5-107","article-title":"Iota-Carrageenan is a potent inhibitor of rhinovirus infection","volume":"5","author":"Grassauer","year":"2008","journal-title":"Virol. J."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Leibbrandt, A., Meier, C., Konig-Schuster, M., Weinmullner, R., Kalthoff, D., Pflugfelder, B., Graf, P., Frank-Gehrke, B., Beer, M., and Fazekas, T. (2010). Iota-carrageenan is a potent inhibitor of influenza A virus infection. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014320"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2147\/IJGM.S120665","article-title":"Amylmetacresol\/2,4-dichlorobenzyl alcohol, hexylresorcinol, or carrageenan lozenges as active treatments for sore throat","volume":"10","author":"Graf","year":"2017","journal-title":"Int. J. Gen. Med."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Morokutti-Kurz, M., Konig-Schuster, M., Koller, C., Graf, C., Graf, P., Kirchoff, N., Reutterer, B., Seifert, J.M., Unger, H., and Grassauer, A. (2015). The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128794"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s11802-012-2107-3","article-title":"Structure and anti-influenza A (H1N1) virus activity of three polysaccharides from Eucheuma denticulatum","volume":"11","author":"Yu","year":"2012","journal-title":"J. Ocean Univ. China"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1099\/0022-1317-68-2-425","article-title":"Protective mechanisms against pulmonary infection with influenza virus. I. Relative contribution of polymorphonuclear leukocytes and of alveolar macrophages to protection during the early phase of intranasal infection","volume":"68","author":"Fujisawa","year":"1987","journal-title":"J. Gen. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1002\/app.37502","article-title":"Preparation and potentialin vivoanti-influenza virus activity of low molecular-weight \u03ba-carrageenans and their derivatives","volume":"127","author":"Tang","year":"2013","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1099\/0022-1317-68-2-419","article-title":"Mechanism of protection during the early phase of a generalized viral infection. II. Contribution of polymorphonuclear leukocytes to protection against intravenous infection with influenza virus","volume":"68","author":"Tsuru","year":"1987","journal-title":"J. Gen. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1099\/0022-1317-64-9-2021","article-title":"Mechanism of protection during the early phase of a generalized viral infection. I. Contribution of phagocytes to protection against ectromelia virus","volume":"64","author":"Tsuru","year":"1983","journal-title":"J. Gen. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Hebar, A., Koller, C., Seifert, J.M., Chabicovsky, M., Bodenteich, A., Bernkop-Schnurch, A., Grassauer, A., and Prieschl-Grassauer, E. (2015). Non-clinical safety evaluation of intranasal iota-carrageenan. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122911"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/1465-9921-11-108","article-title":"Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: A randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold","volume":"11","author":"Eccles","year":"2010","journal-title":"Respir. Res."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Fazekas, T., Eickhoff, P., Pruckner, N., Vollnhofer, G., Fischmeister, G., Diakos, C., Rauch, M., Verdianz, M., Zoubek, A., and Gadner, H. (2012). Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold. BMC Complement. Altern. Med., 12.","DOI":"10.1186\/1472-6882-12-147"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/1465-9921-14-124","article-title":"Efficacy of a carrageenan nasal spray in patients with common cold: A randomized controlled trial","volume":"14","author":"Ludwig","year":"2013","journal-title":"Respir. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/2049-6958-9-57","article-title":"Carrageenan nasal spray in virus confirmed common cold: Individual patient data analysis of two randomized controlled trials","volume":"9","author":"Koenighofer","year":"2014","journal-title":"Multidiscip. Respir. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12931-015-0281-8","article-title":"Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: The ICICC trial","volume":"16","author":"Eccles","year":"2015","journal-title":"Respir. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1002\/ijc.29823","article-title":"Human papillomavirus capsids preferentially bind and infect tumor cells","volume":"138","author":"Kines","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.virol.2013.10.038","article-title":"Preparation and properties of a papillomavirus infectious intermediate and its utility for neutralization studies","volume":"449","author":"Wang","year":"2014","journal-title":"Virology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ygyno.2016.09.003","article-title":"In vitro inhibition of human papillomavirus following use of a carrageenan-containing vaginal gel","volume":"143","author":"Novetsky","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/nm1598","article-title":"Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan","volume":"13","author":"Roberts","year":"2007","journal-title":"Nat. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.3851\/IMP1890","article-title":"The effectiveness of Carraguard, a vaginal microbicide, in protecting women against high-risk human papillomavirus infection","volume":"16","author":"Marais","year":"2011","journal-title":"Antivir. Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/jnci\/djr061","article-title":"Effect of Pap smear collection and carrageenan on cervicovaginal human papillomavirus-16 infection in a rhesus macaque model","volume":"103","author":"Roberts","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.cmi.2018.04.012","article-title":"Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): Interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial","volume":"25","author":"Magnan","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_117","first-page":"6744","article-title":"Impact of a new carrageenan-based vaginal microbicide in a female population with genital HPV-infection: First experimental results","volume":"23","author":"Perino","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1128\/AAC.31.9.1388","article-title":"Polysaccharides as antiviral agents: Antiviral activity of carrageenan","volume":"31","author":"Gonzalez","year":"1987","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12985-018-1045-0","article-title":"Heparan sulfate is an important mediator of Ebola virus infection in polarized epithelial cells","volume":"15","author":"Tamhankar","year":"2018","journal-title":"Virol. J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.antiviral.2012.05.009","article-title":"Prevention of human enterovirus 71 infection by kappa carrageenan","volume":"95","author":"Chiu","year":"2012","journal-title":"Antivir. Res."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Tseligka, E.D., Sobo, K., Stoppini, L., Cagno, V., Abdul, F., Piuz, I., Meylan, P., Huang, S., Constant, S., and Tapparel, C. (2018). A VP1 mutation acquired during an enterovirus 71 disseminated infection confers heparan sulfate binding ability and modulates ex vivo tropism. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007190"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s12560-016-9233-9","article-title":"The Experimental Research (In Vitro) of Carrageenans and Fucoidans to Decrease Activity of Hantavirus","volume":"8","author":"Pavliga","year":"2016","journal-title":"Food Environ. Virol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"9237","DOI":"10.1128\/JVI.01362-16","article-title":"Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection in Human Lung Cells and Airway Tissues","volume":"90","author":"Klimyte","year":"2016","journal-title":"J. Virol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1128\/AAC.30.3.409","article-title":"Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions","volume":"30","author":"Kimberlin","year":"1986","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/18\/9\/435\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:04:41Z","timestamp":1760177081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/18\/9\/435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,21]]},"references-count":124,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["md18090435"],"URL":"https:\/\/doi.org\/10.3390\/md18090435","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,21]]}}}