{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:21:53Z","timestamp":1787030513664,"version":"build-2736575974"},"reference-count":23,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:00:00Z","timestamp":1341100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2012,7]]},"abstract":"\n Background<\/jats:title>\n Human T-cell leukemia virus-1 (HTLV-1) was the first identified human retrovirus and was shown to be associated with diseases such as adult T-cell leukemia lymphoma and tropical spastic paraparesis\/HTLV-1 associated myelopathy. Retroviral proteases (PRs) are essential for viral replication by processing viral Gag and Gag-(Pro)-Pol polyproteins during maturation. Full-length HTLV-1 PR is 125 residues long; whether the C-terminal region is required for catalytic activity is still controversial. In this study, we characterized the effect of C-terminal amino acids of HTLV-1 PR for PR activity and examined the binding of compounds identified by in silico screening. One compound showed inhibition against the virus in infected cells.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Truncated (116-, 121- and 122-residue) forms of HTLV-1 PR were prepared and proteins from expression of the genes were purified. In silico screening was performed by docking small molecules into the active site of HTLV-1 PR. The kinetic constants k\n cat<\/jats:sub>\n , K\n m<\/jats:sub>\n , k\n cat<\/jats:sub>\n \/ K\n m<\/jats:sub>\n and inhibition constants K\n i<\/jats:sub>\n for inhibitors identified by the computational screening were determined. Western blot and ELISA analyses were used to determine the effect of the most potent PR inhibitors on HTLV-1 protein processing in infected cells.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The constructs showed similar catalytic efficiency constants ( k\n cat<\/jats:sub>\n \/ K\n m<\/jats:sub>\n ); thus HTLV-1 PR C-terminal amino acids are not essential for full activity. Computational screening revealed new PR inhibitors and some were shown to be inhibitory in enzyme assays. In HTLV-1-infected cells, one of the small molecules inhibited HTLV-1 gag cleavage and decreased the amount of HTLV-1 p19 produced in the cells.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n We have identified an HTLV-1 PR inhibitor that is biologically functional. Inhibitor screening will continue to develop possible drugs for therapy of HTLV-1 infection.<\/jats:p>\n <\/jats:sec>","DOI":"10.3851\/imp2090","type":"journal-article","created":{"date-parts":[[2012,3,22]],"date-time":"2012-03-22T19:08:19Z","timestamp":1332443299000},"page":"883-892","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Kinetic Characterization of Newly Discovered Inhibitors of Various Constructs of Human T-Cell Leukemia Virus-1 (HTLV-1) Protease and Their Effect on HTLV-1-Infected Cells"],"prefix":"10.1177","volume":"17","author":[{"given":"Ahu","family":"Demir","sequence":"first","affiliation":[{"name":"University of Florida College of Medicine Biochemistry and Molecular Biology, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael M","family":"Oguariri","sequence":"additional","affiliation":[{"name":"Laboratory of Human Retrovirology, Science Applications International Corporation-Frederick Inc., National Cancer Institute Frederick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Magis","sequence":"additional","affiliation":[{"name":"Department of Center of Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Ostrov","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomozumi","family":"Imamichi","sequence":"additional","affiliation":[{"name":"Laboratory of Human Retrovirology, Science Applications International Corporation-Frederick Inc., National Cancer Institute Frederick, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben M","family":"Dunn","sequence":"additional","affiliation":[{"name":"University of Florida College of Medicine Biochemistry and Molecular Biology, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,7,1]]},"reference":[{"key":"bibr1-IMP2090","doi-asserted-by":"publisher","DOI":"10.2174\/138161207780618849"},{"key":"bibr2-IMP2090","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01714.x"},{"key":"bibr3-IMP2090","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-960X(97)90015-1"},{"key":"bibr4-IMP2090","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509335102"},{"key":"bibr5-IMP2090","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1998.14.1007"},{"key":"bibr6-IMP2090","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-75-9-2233"},{"key":"bibr7-IMP2090","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401868200"},{"key":"bibr8-IMP2090","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1992.tb17001.x"},{"key":"bibr9-IMP2090","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.06.087"},{"key":"bibr10-IMP2090","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20071132"},{"key":"bibr11-IMP2090","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.7.5505-5511.1997"},{"key":"bibr12-IMP2090","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.10.6660"},{"key":"bibr13-IMP2090","doi-asserted-by":"publisher","DOI":"10.1021\/bi035701y"},{"key":"bibr14-IMP2090","doi-asserted-by":"publisher","DOI":"10.1006\/bioo.2001.1197"},{"key":"bibr15-IMP2090","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402464"},{"key":"bibr16-IMP2090","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-006-9060-4"},{"key":"bibr17-IMP2090","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bb.06.060177.001055"},{"key":"bibr18-IMP2090","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)60646-5"},{"key":"bibr19-IMP2090","doi-asserted-by":"publisher","DOI":"10.1126\/science.2992081"},{"key":"bibr20-IMP2090","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.2.1011-1020.2003"},{"key":"bibr21-IMP2090","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608150200"},{"key":"bibr22-IMP2090","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8477-8485.2004"},{"key":"bibr23-IMP2090","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240400103"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2090","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:50:44Z","timestamp":1777380644000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP2090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,7]]}},"alternative-id":["10.3851\/IMP2090"],"URL":"https:\/\/doi.org\/10.3851\/imp2090","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7]]}}}