{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:32:05Z","timestamp":1792711925779,"version":"4.5.0"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,4,14]]},"abstract":"<jats:p>\n                    To prevent sexually transmitted HIV, the most desirable active ingredients of microbicides are antiretrovirals (ARVs) that directly target viral entry and avert infection at mucosal surfaces. However, most promising ARV entry inhibitors are biologicals, which are costly to manufacture and deliver to resource-poor areas where effective microbicides are urgently needed. Here, we report a manufacturing breakthrough for griffithsin (GRFT), one of the most potent HIV entry inhibitors. This red algal protein was produced in multigram quantities after extraction from\n                    <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                    plants transduced with a tobacco mosaic virus vector expressing GRFT. Plant-produced GRFT (GRFT-P) was shown as active against HIV at picomolar concentrations, directly virucidal via binding to HIV envelope glycoproteins, and capable of blocking cell-to-cell HIV transmission. GRFT-P has broad-spectrum activity against HIV clades A, B, and C, with utility as a microbicide component for HIV prevention in established epidemics in sub-Saharan Africa, South Asia, China, and the industrialized West. Cognizant of the imperative that microbicides not induce epithelial damage or inflammatory responses, we also show that GRFT-P is nonirritating and noninflammatory in human cervical explants and in vivo in the rabbit vaginal irritation model. Moreover, GRFT-P is potently active in preventing infection of cervical explants by HIV-1 and has no mitogenic activity on cultured human lymphocytes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0901506106","type":"journal-article","created":{"date-parts":[[2009,3,30]],"date-time":"2009-03-30T21:44:29Z","timestamp":1238449469000},"page":"6099-6104","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":226,"title":["Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component"],"prefix":"10.1073","volume":"106","author":[{"given":"Barry R.","family":"O'Keefe","sequence":"first","affiliation":[{"name":"Molecular Targets Development Program, National Cancer Institute at Frederick, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakhrieh","family":"Vojdani","sequence":"additional","affiliation":[{"name":"Intrucept Biomedicine, Owensboro, KY 42301;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Buffa","sequence":"additional","affiliation":[{"name":"Saint George's Hospital Medical School, University of London, London SW17 0RE, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Shattock","sequence":"additional","affiliation":[{"name":"Saint George's Hospital Medical School, University of London, London SW17 0RE, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Montefiori","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, NC 27708;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Bakke","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, CA 94025;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Mirsalis","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, CA 94025;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lisa","family":"d'Andrea","sequence":"additional","affiliation":[{"name":"SRI International, Menlo Park, CA 94025;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Hume","sequence":"additional","affiliation":[{"name":"Kentucky Bioprocessing, Owensboro, KY 42301;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Bratcher","sequence":"additional","affiliation":[{"name":"Kentucky Bioprocessing, Owensboro, KY 42301;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie J.","family":"Saucedo","sequence":"additional","affiliation":[{"name":"Molecular Targets Development Program, National Cancer Institute at Frederick, Frederick, MD 21702;"},{"name":"SAIC-Frederick, Frederick, MD 21702; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"McMahon","sequence":"additional","affiliation":[{"name":"Molecular Targets Development Program, National Cancer Institute at Frederick, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory P.","family":"Pogue","sequence":"additional","affiliation":[{"name":"Intrucept Biomedicine, Owensboro, KY 42301;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Intrucept Biomedicine, Owensboro, KY 42301;"},{"name":"Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,4,14]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2302"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.01.007"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm833"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04055"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802666105"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/088922204322749459"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/088922203322230897"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099288"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4742fje"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708841104"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411122200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2006.05.017"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21336"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0684.2007.00242.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9579"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803636105"},{"key":"e_1_3_3_17_2","first-page":"12.11.1","volume-title":"Current Protocols in Immunology","author":"Montefiori DC","year":"2005","unstructured":"DC Montefiori, Evaluating neutralizing antibodies against HIV, SIV, and SHIV in luciferase reporter gene assays. Current Protocols in Immunology, eds JE Coligan, et al. (John Wiley & Sons, New York), pp. 12.11.1\u201312.11.17 (2005)."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01730-06"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.16.10108-10125.2005"},{"key":"e_1_3_3_20_2","first-page":"1065","article-title":"Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue","volume":"199","author":"Hu Q","year":"2004","unstructured":"Q Hu, et al., Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. J Virol 199, 1065\u20131075 (2004).","journal-title":"J Virol"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.05.023"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.713-723.2006"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.12.5577-5586.2000"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.004358-0"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0200085"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200405010-00001"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.59.061206.112737"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2005.10.014"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505763102"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32805e8727"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.17.11179-11186.2005"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0901506106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:01:10Z","timestamp":1649786470000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0901506106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,14]]},"references-count":31,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2009,4,14]]}},"alternative-id":["10.1073\/pnas.0901506106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0901506106","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1157851.619097","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,14]]},"assertion":[{"value":"2008-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-04-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}