{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T07:42:00Z","timestamp":1781509320066,"version":"3.54.1"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["AS262Z02656P"],"award-info":[{"award-number":["AS262Z02656P"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Since combination antiretroviral therapy (cART) was introduced to treat human immunodeficiency virus type-1 (HIV-1)\/acquired immunodeficiency syndrome (AIDS), the AIDS mortality rate has markedly decreased, and convalescence in individuals with HIV has improved drastically. However, sexual transmission has made HIV-1 a global epidemic. Sacran is a megamolecular polysaccharide extracted from cyanobacterium Aphanothece sacrum that exhibits numerous desirable characteristics for transdermic applications, such as safety as a biomaterial, a high moisture retention effect, the ability to form a film and hydrogel, and an anti-inflammatory effect. In this study, we evaluated the anti-HIV-1 effects in sacran as a barrier to HIV-1 transmission. Sacran inhibited HIV-1 infection and envelope-dependent cell-to-cell fusion. Moreover, we used a Transwell assay to confirm that sacran inhibited viral diffusion and captured viruses. The synergistic effects of sacran and other anti-HIV infection drugs were also evaluated. HIV-1 infections can be reduced through the synergistic effects of sacran and anti-HIV-1 drugs. Our study suggests using sacran gel to provide protection against HIV-1 transmission.<\/jats:p>","DOI":"10.3390\/v16091501","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T09:15:07Z","timestamp":1727082907000},"page":"1501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluating the Use of Sacran, a Polysaccharide Isolated from Aphanothece sacrum, as a Possible Microbicide for Preventing HIV-1 Infection"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4757-7128","authenticated-orcid":false,"given":"Kouki","family":"Matsuda","sequence":"first","affiliation":[{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan"},{"name":"Division of Antiviral Therapy, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusho","family":"Kariya","sequence":"additional","affiliation":[{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Maeda","sequence":"additional","affiliation":[{"name":"Division of Antiviral Therapy, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-5206","authenticated-orcid":false,"given":"Seiji","family":"Okada","sequence":"additional","affiliation":[{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2024, September 21). 2023 Global AIDS Update. Available online: http:\/\/www.unaids.org\/en."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"CMWH-S10353","DOI":"10.4137\/CMWH.S10353","article-title":"Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection","volume":"7","author":"McConville","year":"2014","journal-title":"Clin. Med. Insights Womens Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1111\/tmi.13401","article-title":"Effectiveness of Vaginal Microbicides in Preventing HIV Transmission","volume":"25","author":"Musekiwa","year":"2020","journal-title":"Trop. Med. Int. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/COH.0000000000000746","article-title":"How Could HIV-1 Drug Resistance Impact Preexposure Prophylaxis for HIV Prevention?","volume":"17","author":"Parikh","year":"2022","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S1473-3099(08)70254-8","article-title":"Vaginal Microbicides and the Prevention of HIV Transmission","volume":"8","author":"Cutler","year":"2008","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10531","DOI":"10.1073\/pnas.0802666105","article-title":"Tropism-Independent Protection of Macaques against Vaginal Transmission of Three SHIVs by the HIV-1 Fusion Inhibitor T-1249","volume":"105","author":"Veazey","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa1402269","article-title":"Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women","volume":"372","author":"Marrazzo","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1021\/ma800307w","article-title":"Supergiant Ampholytic Sugar Chains with Imbalanced Charge Ratio Form Saline Ultra-Absorbent Hydrogels","volume":"41","author":"Maiko","year":"2008","journal-title":"Macromolecules"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8526","DOI":"10.1021\/la8036956","article-title":"Cyanobacterial Megamolecule Sacran Efficiently Forms LC Gels with Very Heavy Metal Ions","volume":"25","author":"Okajima","year":"2009","journal-title":"Langmuir"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1021\/bm100231q","article-title":"Cyanobacterial Polysaccharide Gels with Efficient Rare-Earth-Metal Sorption","volume":"11","author":"Okajima","year":"2010","journal-title":"Biomacromolecules"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1021\/bm101012u","article-title":"Gelation Behavior by the Lanthanoid Adsorption of the Cyanobacterial Extracellular Polysaccharide","volume":"11","author":"Okajima","year":"2010","journal-title":"Biomacromolecules"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1248\/cpb.c14-00053","article-title":"Potential Use of a Megamolecular Polysaccharide Sacran as a Hydrogel-Based Sustained Release System","volume":"62","author":"Motoyama","year":"2014","journal-title":"Chem. Pharm. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Puluhulawa, L.E., Joni, I.M., Mohammed, A.F.A., Arima, H., and Wathoni, N. (2021). The Use of Megamolecular Polysaccharide Sacran in Food and Biomedical Applications. Molecules, 26.","DOI":"10.3390\/molecules26113362"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"30083","DOI":"10.1074\/jbc.M414360200","article-title":"Isolation of TAK-779-Resistant HIV-1 from an R5 HIV-1 GP120 V3 Loop Library","volume":"280","author":"Yusa","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1128\/jvi.70.3.1340-1354.1996","article-title":"Molecular Determinants of Acute Single-Cell Lysis by Human Immunodeficiency Virus Type 1","volume":"70","author":"Cao","year":"1996","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.bbrc.2014.12.102","article-title":"Inhibition of HIV-1 Entry by the Tricyclic Coumarin GUT-70 through the Modification of Membrane Fluidity","volume":"457","author":"Matsuda","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/j.bmcl.2014.03.041","article-title":"Cepharanthine Inhibited HIV-1 Cell-Cell Transmission and Cell-Free Infection via Modification of Cell Membrane Fluidity","volume":"24","author":"Matsuda","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1128\/AAC.00270-09","article-title":"Potent Activity of a Nucleoside Reverse Transcriptase Inhibitor, 4\u2032-Ethynyl-2-Fluoro-2\u2032-Deoxyadenosine, against Human Immunodeficiency Virus Type 1 Infection in a Model Using Human Peripheral Blood Mononuclear Cell-Transplanted NOD\/SCID Janus Kinase 3 Knockout Mice","volume":"53","author":"Hattori","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1084\/jem.186.8.1383","article-title":"Inhibition of T-Tropic HIV Strains by Selective Antagonization of the Chemokine Receptor CXCR4","volume":"186","author":"Schols","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1089\/aid.1993.9.1051","article-title":"A Synthetic Peptide from HIV-1 gp41 Is a Potent Inhibitor of Virus-Mediated Cell-Cell Fusion","volume":"9","author":"Wild","year":"1993","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1128\/AAC.39.12.2602","article-title":"L-743, 726 (DMP-266): A Novel, Highly Potent Nonnucleoside Inhibitor of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase","volume":"39","author":"Young","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.antiviral.2010.08.006","article-title":"Semi-Solid Gels Function as Physical Barriers to Human Immunodeficiency Virus Transport In Vitro","volume":"88","author":"Lai","year":"2010","journal-title":"Antiviral Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chutiwitoonchai, N., Hiyoshi, M., Mwimanzi, P., Ueno, T., Adachi, A., Ode, H., Sato, H., Fackler, O.T., Okada, S., and Suzu, S. (2011). The Identification of a Small Molecule Compound That Reduces HIV-1 Nef-Mediated Viral Infectivity Enhancement. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027696"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/0165-6147(83)90490-X","article-title":"Analysis of Combined Drug Effects\u2014A New Look at a Very Old Problem","volume":"4","author":"Chou","year":"1983","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: The Combined Effects of Multiple Drugs or Enzyme Inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzyme Regul."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4721","DOI":"10.1128\/AAC.49.11.4721-4732.2005","article-title":"Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity","volume":"49","author":"Dorr","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1086\/378302","article-title":"Enfuvirtide (T-20): A Novel Human Immunodeficiency Virus Type 1 Fusion Inhibitor","volume":"37","author":"Cervia","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nrd1331","article-title":"Enfuvirtide: The First Therapy to Inhibit the Entry of HIV-1 into Host CD4 Lymphocytes","volume":"3","author":"Matthews","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature04055","article-title":"Protection of Macaques from Vaginal SHIV Challenge by Vaginally Delivered Inhibitors of Virus-Cell Fusion","volume":"438","author":"Veazey","year":"2005","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.virol.2007.03.001","article-title":"Entry Inhibitor-Based Microbicides Are Active In Vitro against HIV-1 Isolates from Multiple Genetic Subtypes","volume":"364","author":"Ketas","year":"2007","journal-title":"Virology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.3390\/v2061306","article-title":"Cell-to-Cell Spread of Retroviruses","volume":"2","author":"Sattentau","year":"2010","journal-title":"Viruses"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1016\/0006-2952(94)90254-2","article-title":"Antiviral Activity of a Sulphated Polysaccharide from the Red Seaweed Nothogenia Fastigiata","volume":"47","author":"Damonte","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.anai.2011.10.013","article-title":"Anti-Inflammatory Effects of Sacran, a Novel Polysaccharide from Aphanothece Sacrum, on 2,4,6-Trinitrochlorobenzene-Induced Allergic Dermatitis In Vivo","volume":"108","author":"Ngatu","year":"2012","journal-title":"Ann. Allergy Asthma Immunol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/9\/1501\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:02:55Z","timestamp":1760112175000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/9\/1501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,23]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["v16091501"],"URL":"https:\/\/doi.org\/10.3390\/v16091501","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,23]]}}}