{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:09:30Z","timestamp":1790716170027,"version":"4.1.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"13","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            A structurally novel candidate microbicide, PPCM, which is formed from the reaction of\n            <jats:sc>d,l<\/jats:sc>\n            -mandelic acid with sulfuric acid, provides activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) and is not cytotoxic. The objectives of the current studies were to comprehensively evaluate the activity of PPCM in cell and explant cultures, explore the possibility of combining PPCM with HIV-specific reverse transcriptase inhibitors, and evaluate the efficacy of a formulated gel against genital herpes in a murine model. PPCM inhibited infection by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical and endocervical tissue explants exposed to HIV-1\n            <jats:sub>BaL<\/jats:sub>\n            in the presence of PPCM were protected (50% inhibitory concentrations [IC\n            <jats:sub>50<\/jats:sub>\n            ] of 3.9 \u03bcg\/ml for ectocervix and 3.1 \u03bcg\/ml for endocervix), and transfer of virus to target T cells via migratory cells was significantly impaired (IC\n            <jats:sub>50<\/jats:sub>\n            of 35.7 \u03bcg\/ml for ectocervix and 54.6 \u03bcg\/ml for endocervix). The drug also blocked infection by cell-associated virus. Combinations of PPCM with UC-781 or PMPA in vitro exhibited additive anti-HIV activity. PPCM was incorporated into stable, low-pH gel formulations at concentrations of 0.4% and 4%. Both gels prevented genital herpesvirus infection in mice, even when virus was introduced in human seminal plasma. The abilities of PPCM to inhibit primary HIV isolates, reduce infection by cell-associated virus, and transfer of HIV from migratory to T cells, combined with the complete protection provided by formulated gel against genital herpes, indicate that this drug is an excellent candidate for inclusion in a combination microbicide and would provide protection against both HIV and HSV.\n          <\/jats:p>","DOI":"10.1128\/jvi.00335-08","type":"journal-article","created":{"date-parts":[[2008,4,24]],"date-time":"2008-04-24T00:45:06Z","timestamp":1208997906000},"page":"6576-6584","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model"],"prefix":"10.1128","volume":"82","author":[{"given":"Pedro M. M.","family":"Mesquita","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"},{"name":"Departments of Pediatrics"},{"name":"Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah S.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"},{"name":"Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Manlow","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Fischetti","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marla J.","family":"Keller","sequence":"additional","affiliation":[{"name":"Medicine, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsy C.","family":"Herold","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"},{"name":"Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Shattock","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.0234"},{"key":"e_1_3_2_3_2","first-page":"394","volume":"50","year":"1996","unstructured":"Balzarini, J., H. Pelemans, S. Aquaro, C. F. Perno, M. Witvrouw, D. Schols, E. De Clercq, and A. Karlsson. 1996. Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication. Mol. Pharmacol.50:394-401.","journal-title":"Mol. Pharmacol."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01303-06"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000232228.88511.0b"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/368020"},{"key":"e_1_3_2_7_2","unstructured":"Abstr. 15th Conf. Retrovir. Oppor. Infect. 2008"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.08.048"},{"key":"e_1_3_2_9_2","first-page":"294","volume":"41","year":"2000","unstructured":"Chang, T. T., and T. C. Chou. 2000. Rational approach to the clinical protocol design for drug combinations: a review. Acta Paediatr. Taiwan41:294-302.","journal-title":"Acta Paediatr. Taiwan"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.6.2025-2036.2004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(84)90007-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe068302"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200404150-00001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/319676"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.10.3834-3844.2004"},{"key":"e_1_3_2_16_2","unstructured":"Abstr. 14th Conf. Retrovir. Oppor. Infect. 2007"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.olq.0000223287.46097.4b"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.17.11179-11186.2005"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000198081.09337.a7"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60313-4"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.12.5577-5586.2000"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.22.11236-11244.2002"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.12.2776"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022212"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/498533"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)66969-6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000222075.83490.ca"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2006.22.411"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02851-06"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.4.1948-1960.2000"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062607"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.9.5386-5399.2005"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1086\/522606"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001312"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.4.2855-2864.1998"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1086\/516541"},{"key":"e_1_3_2_37_2","unstructured":"Abstr. 15th Conf. Retrovir. Oppor. Infect. 2008"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.07.029"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1080\/1061186042000203574"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3002(63)90513-4"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1086\/510748"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11079-8"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500911200"},{"key":"e_1_3_2_44_2","unstructured":"Abstr. 15th Conf. Retrovir. Oppor. Infect. 2008"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.09.028"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1086\/379248"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod66.4.886"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(02)04210-3"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8356453"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00335-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00335-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T11:52:51Z","timestamp":1646481171000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00335-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7]]},"references-count":48,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2008,7]]}},"alternative-id":["10.1128\/JVI.00335-08"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00335-08","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7]]},"assertion":[{"value":"2008-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-04-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}