{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T02:43:32Z","timestamp":1781059412566,"version":"3.54.1"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Influenza viruses of types A and B cause periodic pandemics in the human population. The antiviral drugs approved to combat influenza virus infections are currently limited. We have investigated an effective novel inhibitor of human influenza A and B viruses, triazavirine {2-methylthio-6-nitro-1,2,4-triazolo[5,1-c]-1,2,4-triazine-7(4I\u0301)-one} (TZV). TZV suppressed the replication of influenza virus in cell culture and in chicken chorioallantoic membranes, and it protected mice from death caused by type A and B influenza viruses. TZV was also effective against a rimantadine-resistant influenza virus strain and against avian influenza A virus H5N1 strains. The pharmacokinetic parameters and bioavailability of TZV were calculated after the administration of TZV to rabbits. The TZV metabolite AMTZV {2-methylthio-6-amino-1,2,4-triazolo[5,1-\n            <jats:italic>s<\/jats:italic>\n            ]-1,2,4-triazin(e)-7(4I\u0301)-one} was discovered in I\u0301A\u030aK 293T and Huh7 cell cultures, a liver homogenate, and rabbit blood after intragastric administration of TZV. AMTZV was nontoxic and inactive as an inhibitor of influenza virus in cell culture. Most likely, this metabolite is a product of TZV elimination.\n          <\/jats:p>","DOI":"10.1128\/aac.01186-09","type":"journal-article","created":{"date-parts":[[2010,3,2]],"date-time":"2010-03-02T04:54:26Z","timestamp":1267505666000},"page":"2017-2022","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":65,"title":["Antiviral Properties, Metabolism, and Pharmacokinetics of a Novel Azolo-1,2,4-Triazine-Derived Inhibitor of Influenza A and B Virus Replication"],"prefix":"10.1128","volume":"54","author":[{"given":"Inna","family":"Karpenko","sequence":"first","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Deev","sequence":"additional","affiliation":[{"name":"Postovsky Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, Ekaterinburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Kiselev","sequence":"additional","affiliation":[{"name":"Research Institute of Influenza, Russian Academy of Medical Sciences, St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerey","family":"Charushin","sequence":"additional","affiliation":[{"name":"Postovsky Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, Ekaterinburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Rusinov","sequence":"additional","affiliation":[{"name":"Postovsky Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, Ekaterinburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugeney","family":"Ulomsky","sequence":"additional","affiliation":[{"name":"Postovsky Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, Ekaterinburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Deeva","sequence":"additional","affiliation":[{"name":"Research Institute of Influenza, Russian Academy of Medical Sciences, St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Yanvarev","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Kochetkov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Chupakhin","sequence":"additional","affiliation":[{"name":"Postovsky Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, Ekaterinburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Kukhanova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Sodium salt dihydrate possessing antiviral activity. 2007"},{"key":"e_1_3_2_3_2","first-page":"358","volume":"446","year":"2007","unstructured":"Fuyuno, I. 2007. Tamiflu side effects come under scrutiny. Nature446:358-359.","journal-title":"Nature"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.epirev.a017917"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.335.7614.sgp59"},{"key":"e_1_3_2_6_2","first-page":"44","year":"1996","unstructured":"Hay, A. 1996. Amantadine and rimantadine\u2014mechanisms, p. 44-58. In D. Richman (ed.), Antiviral drug resistance. John Wiley and Sons Ltd., Chichester, United Kingdom.","journal-title":"Antiviral drug resistance."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1985.tb04038.x"},{"key":"e_1_3_2_8_2","first-page":"5","year":"2004","unstructured":"Hayden, F. 2004. Annex 5: considerations for the use of antivirals during an influenza pandemic, p.5-1-5-18. InWHO guidelines on the use of vaccines and antivirals during influenza pandemics. World Health Organization, Geneva, Switzerland. http:\/\/www.wpro.who.int\/internet\/resources.ashx\/CSR\/Publications\/11_29_01_A.pdf .","journal-title":"WHO guidelines on the use of vaccines and antivirals during influenza pandemics."},{"key":"e_1_3_2_9_2","first-page":"119","volume":"176","year":"1992","unstructured":"Hayden, F. G., and A. J. Hay. 1992. Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine. Curr. Top. Microbiol. Immunol.176:119-130.","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804958105"},{"key":"e_1_3_2_11_2","first-page":"147","volume":"82","year":"2002","unstructured":"Johnston, S. L. 2002. Anti-influenza therapies. Virus Res.82:147-152.","journal-title":"Virus Res."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.022269"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(08)60520-5"},{"key":"e_1_3_2_14_2","first-page":"112","volume":"2","year":"2003","unstructured":"Kuznetsov, O. K., and O. I. Kiselev. 2003. Influenza viruses with pandemic potential and measures to prevent their emergence: facts, hypothesis. Med. Acad. J.2:112-121.","journal-title":"Med. Acad. J."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/scientificamerican0199-78"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(00)00123-6"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.2.1099-1106.1995"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2008.02.005"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39240.497025.80"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e318168b739"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050740"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/314903"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","unstructured":"NIH publication 86\/609\/EEC. 1986","DOI":"10.1016\/S0002-8223(21)03989-4"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp058068"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2008.01.003"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.1.200-204.2000"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902548106"},{"key":"e_1_3_2_28_2","first-page":"493","volume":"27","year":"1938","unstructured":"Reed, L., and H. Muench. 1938. A simple method of estimating fifty percent endpoints. Am. J. Hyg.27:493-497.","journal-title":"Am. J. Hyg."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.029470"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06531"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03161197"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2004.03.001"},{"key":"e_1_3_2_33_2","first-page":"1613","volume":"165","year":"2008","unstructured":"Smith, E. J. 2008. Amantadine-induced psychosis in a young healthy patient. Am. J. Psychiatr.165:1613.","journal-title":"Am. J. Psychiatr."},{"key":"e_1_3_2_34_2","first-page":"674","volume":"5","year":"1992","unstructured":"Ulomskii, E. N., E. V. Tsoi, V. L. Rusinov, O. N. Chupakhin, G. L. Kalb, and I. M. Sosonkin. 1992. Reduction of nitro derivatives of azolo[5,1-c][1,2,4]triazines. Khimiya Geterotsiklicheskikh Soedinenii5:674-677. (In Russian.)","journal-title":"Khimiya Geterotsiklicheskikh Soedinenii"},{"key":"e_1_3_2_35_2","first-page":"711","volume":"24","year":"1961","unstructured":"Veeraraghavan, N., M. W. Kiritikar, and T. T. Sreevalsan. 1961. Studies on the cultivation of influenza virus in vitro. Bull. W. H. O.24:711-722.","journal-title":"Bull. W. H. O."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.9.5585-5594.1993"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"i5","DOI":"10.1093\/jac\/dki018","volume":"55","year":"2005","unstructured":"Ward, P., I. Small, J. Smith, and R. Dutkowski. 2005. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J. Antimicrob. Chemother.55(Suppl. 1):i5-i21.","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01186-09","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01186-09","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:22:53Z","timestamp":1645474973000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01186-09"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,5]]}},"alternative-id":["10.1128\/AAC.01186-09"],"URL":"https:\/\/doi.org\/10.1128\/aac.01186-09","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5]]},"assertion":[{"value":"2009-08-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-02-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}