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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vavilov</journal-id><journal-title-group><journal-title xml:lang="ru">Вавиловский журнал генетики и селекции</journal-title><trans-title-group xml:lang="en"><trans-title>Vavilov Journal of Genetics and Breeding</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2500-3259</issn><publisher><publisher-name>Institute of Cytology and Genetics of Siberian Branch of the RAS</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">vavilov-50</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Статьи</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>ПОДАВЛЕНИЕ РЕПЛИКАЦИИ СУБГЕНОМНОГО РНК РЕПЛИКОНА ВИРУСА ГЕПАТИТА С ИНГИБИТОРОМ NS3 ПРОТЕАЗЫ SCH 503034 В Huh-7 КЛЕТКАХ: СТОХАСТИЧЕСКАЯ МОДЕЛЬ</article-title><trans-title-group xml:lang="en"><trans-title>SUPPRESSION OF SUBGENOMIC HEPATITIS C VIRUS RNA REPLICON REPLICATION IN Huh-7 CELLS BY THE NS3 PROTEASE INHIBITOR SCH5030334: A STOCHASTIC MATHEMATICAL MODEL</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мищенко</surname><given-names>Е. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Mishchenko</surname><given-names>E. L.</given-names></name></name-alternatives><email xlink:type="simple">elmish@bionet.nsc.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Иванисенко</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Ivanisenko</surname><given-names>N. V.</given-names></name></name-alternatives><email xlink:type="simple">elmish@bionet.nsc.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Акбердин</surname><given-names>И. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Akberdin</surname><given-names>I. R.</given-names></name></name-alternatives><email xlink:type="simple">elmish@bionet.nsc.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Деменков</surname><given-names>П. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Demenkov</surname><given-names>P. S.</given-names></name></name-alternatives><email xlink:type="simple">elmish@bionet.nsc.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лихошвай</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Likhoshvai</surname><given-names>V. A.</given-names></name></name-alternatives><email xlink:type="simple">elmish@bionet.nsc.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Колчанов</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kolchanov</surname><given-names>N. A.</given-names></name></name-alternatives><email xlink:type="simple">elmish@bionet.nsc.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Иванисенко</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ivanisenko</surname><given-names>V. A.</given-names></name></name-alternatives><email xlink:type="simple">elmish@bionet.nsc.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, Россия<country>Россия</country></aff><aff xml:lang="en">Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Федеральное государственное бюджетное учреждение науки Институт цитологии и генетики Сибирского отделения РАН, Новосибирск, Россия&#13;
Новосибирский государственный университет, Новосибирск, Россия<country>Россия</country></aff><aff xml:lang="en">Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia&#13;
Novosibirsk State University, Novosibirsk, Russia<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>12</day><month>12</month><year>2014</year></pub-date><volume>16</volume><issue>2</issue><fpage>339</fpage><lpage>347</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Мищенко Е.Л., Иванисенко Н.В., Акбердин И.Р., Деменков П.С., Лихошвай В.А., Колчанов Н.А., Иванисенко В.А., 2014</copyright-statement><copyright-year>2014</copyright-year><copyright-holder xml:lang="ru">Мищенко Е.Л., Иванисенко Н.В., Акбердин И.Р., Деменков П.С., Лихошвай В.А., Колчанов Н.А., Иванисенко В.А.</copyright-holder><copyright-holder xml:lang="en">Mishchenko E.L., Ivanisenko N.V., Akberdin I.R., Demenkov P.S., Likhoshvai V.A., Kolchanov N.A., Ivanisenko V.A.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://vavilov.elpub.ru/jour/article/view/50">https://vavilov.elpub.ru/jour/article/view/50</self-uri><abstract><p>Вирус гепатита С (ВГС) вызывает опасное заболевание печени, часто сопровождающееся циррозом и гепатоклеточной карциномой. Против ВГС до сих пор нет эффективной терапии. Для предсказания эффективности действия новых потенциальных лекарств, направленных против ВГС, актуально применение математического моделирования. Впервые предложена стохастическая модель репликации субгеномного РНК репликона ВГС в Huh-7 клетках в присутствии ингибитора NS3 протеазы ВГС SCH 503034. Модель описывает экспериментально полученные кинетики подавления вирусной РНК в присутствии разных концентраций SCH 503034 и может применяться для разработки оптимальных стратегий подавления РНК ВГС в Huh-7 клетках.</p></abstract><trans-abstract xml:lang="en"><p>Hepatitis C virus (HCV) causes a severe liver disease frequentlyassociatedwith cirrhosis andhepatocellular carcinoma. No effective anti-HCVtherapyis available so far. Thus, it is pertinent to applymathematical modelingto prediction ofthe efficiencyofnew candidate pharmaceuticals. Astochastic mathematical model for subgenomic HCVreplicon replication in Huh-7 cells with the presence ofthe HCVNS3 protease inhibitor SCH 503034 is proposed. The model describes the experimental kinetic curves ofviral RNAsuppression at various SCH 503034 concentrations. It is applicable to the development ofapproaches to HCVRNAsuppression in Huh-7 cells.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>вирус гепатита С</kwd><kwd>субгеномный репликон</kwd><kwd>математическое моделирование</kwd><kwd>эффективность лекарств</kwd></kwd-group><kwd-group xml:lang="en"><kwd>hepatitis C virus</kwd><kwd>subgenomic replicon</kwd><kwd>mathematical modeling</kwd><kwd>effectiveness of drugs</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Castro C., Arnold J.J., Cameron C.E. Incorporation fidelity of the viral RNA-dependent RNA polymerase: a kinetic, thermodynamic and structural perspective // Virus. Res. 2005. V. 107. P. 141–149.</mixed-citation><mixed-citation xml:lang="en">Castro C., Arnold J.J., Cameron C.E. Incorporation fidelity of the viral RNA-dependent RNA polymerase: a kinetic, thermodynamic and structural perspective // Virus. Res. 2005. V. 107. P. 141–149.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Dahari H., Ribeiro R.M., Rice C.M., Perelson A.S. Mathematical modeling of subgenomic hepatitis C viral replication in Huh-7 cells // J. Virol. 2007. V. 81. P. 750–760.</mixed-citation><mixed-citation xml:lang="en">Dahari H., Ribeiro R.M., Rice C.M., Perelson A.S. Mathematical modeling of subgenomic hepatitis C viral replication in Huh-7 cells // J. Virol. 2007. V. 81. P. 750–760.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Egger D., Wölk B., Gosert R. et al. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex // J. Virol. 2002. V. 76. P. 5974–5984.</mixed-citation><mixed-citation xml:lang="en">Egger D., Wölk B., Gosert R. et al. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex // J. Virol. 2002. V. 76. P. 5974–5984.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Gillespie D.T. General method for numerically simulating stochastic time evolution of coupled chemical reactions // J. Comput. Phys. 1976. V. 22. P. 403–434.</mixed-citation><mixed-citation xml:lang="en">Gillespie D.T. General method for numerically simulating stochastic time evolution of coupled chemical reactions // J. Comput. Phys. 1976. V. 22. P. 403–434.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Kieffer T.L., Sarrazin C., Miller J.S. et al. Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients // Hepatology. 2007. V. 46. P. 631–639.</mixed-citation><mixed-citation xml:lang="en">Kieffer T.L., Sarrazin C., Miller J.S. et al. Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients // Hepatology. 2007. V. 46. P. 631–639.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Lin C., Pragai B.M., Grakoui A. et al. Hepatitis C virus NS3 serine proteinase: trans-cleavage requirements and processing kinetics // J. Virol. 1994. V. 68. P. 8147–8157.</mixed-citation><mixed-citation xml:lang="en">Lin C., Pragai B.M., Grakoui A. et al. Hepatitis C virus NS3 serine proteinase: trans-cleavage requirements and processing kinetics // J. Virol. 1994. V. 68. P. 8147–8157.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Lohmann V., Korner F., Koch J. et al. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line // Science. 1999. V. 285. P. 110–113.</mixed-citation><mixed-citation xml:lang="en">Lohmann V., Korner F., Koch J. et al. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line // Science. 1999. V. 285. P. 110–113.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Malcolm B.A., Liu R., Lahser F. et al. SCH 503034, a mechanism-based inhibitor of hepatitis C virus NS3 protease, suppresses polyprotein maturation and enhances the antiviral activity of alpha interferon in replicon cells // Antimicrob. Agents. Chemother. 2006. V. 50. P. 1013–1020.</mixed-citation><mixed-citation xml:lang="en">Malcolm B.A., Liu R., Lahser F. et al. SCH 503034, a mechanism-based inhibitor of hepatitis C virus NS3 protease, suppresses polyprotein maturation and enhances the antiviral activity of alpha interferon in replicon cells // Antimicrob. Agents. Chemother. 2006. V. 50. P. 1013–1020.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Miller S., Krijnse-Locker J. Modification of intracellular membrane structures for virus replication // Nat. Rev. Microbiol. 2008. V. 6. P. 363–374.</mixed-citation><mixed-citation xml:lang="en">Miller S., Krijnse-Locker J. Modification of intracellular membrane structures for virus replication // Nat. Rev. Microbiol. 2008. V. 6. P. 363–374.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Mishchenko E.L., Bezmaternykykh K.D., Likhoshvai V.A. et al. Mathematical model for suppression of subgenomic hepatitis C virus RNA replication in cell culture // J. Bioinform. Comput. Biol. 2007. V. 5. P. 593–609.</mixed-citation><mixed-citation xml:lang="en">Mishchenko E.L., Bezmaternykykh K.D., Likhoshvai V.A. et al. Mathematical model for suppression of subgenomic hepatitis C virus RNA replication in cell culture // J. Bioinform. Comput. Biol. 2007. V. 5. P. 593–609.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Moradpdpour D., Gosert R., Egger D. et al. Membrane association of hepatitis C virus nonstructural proteins and identification of the membrane alteration that harbors the viral replication complex // Antiviral. Res. 2003. V. 60. P. 103–109.</mixed-citation><mixed-citation xml:lang="en">Moradpdpour D., Gosert R., Egger D. et al. Membrane association of hepatitis C virus nonstructural proteins and identification of the membrane alteration that harbors the viral replication complex // Antiviral. Res. 2003. V. 60. P. 103–109.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Moriishi K., Matsuura Y. Host factors involved in the replication of hepatitis C virus // Rev. Med. Virol. 2007. V. 17. P. 343–354.</mixed-citation><mixed-citation xml:lang="en">Moriishi K., Matsuura Y. Host factors involved in the replication of hepatitis C virus // Rev. Med. Virol. 2007. V. 17. P. 343–354.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Nakabayashi J. A compartmentalization model of hepatitis C virus replication: An appropriate distribution of HCV RNA for the effective replication // J. Theor. Biol. 2012. V. 300. P. 110–117.</mixed-citation><mixed-citation xml:lang="en">Nakabayashi J. A compartmentalization model of hepatitis C virus replication: An appropriate distribution of HCV RNA for the effective replication // J. Theor. Biol. 2012. V. 300. P. 110–117.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Pietschmann T., Lohmann V., Rutter G. et al. Characterization of cell lines carrying self-replicating hepatitis C virus RNAs // J. Virol. 2001. V. 75. P. 1252–1264.</mixed-citation><mixed-citation xml:lang="en">Pietschmann T., Lohmann V., Rutter G. et al. Characterization of cell lines carrying self-replicating hepatitis C virus RNAs // J. Virol. 2001. V. 75. P. 1252–1264.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Quinkert D., Bartenschlager R., Lohmann V. Quantitative analysis of the hepatitis C virus replication complex // J. Virol. 2005. V. 79. P. 13594–13605.</mixed-citation><mixed-citation xml:lang="en">Quinkert D., Bartenschlager R., Lohmann V. Quantitative analysis of the hepatitis C virus replication complex // J. Virol. 2005. V. 79. P. 13594–13605.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Reiss S., Rebhan I., Backes P. et alal. Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment // Cell Host Microbe. 2011. V. 9. P. 32–45.</mixed-citation><mixed-citation xml:lang="en">Reiss S., Rebhan I., Backes P. et alal. Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment // Cell Host Microbe. 2011. V. 9. P. 32–45.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Robinson M., Tian Y., Delaney W.E. 4th, Greenstein A.E. Preexisting drug-resistance mutations reveal unique barriers to resistance for distinct antivirals // Proc. Natl Acad. Sci. USA. 2011. V. 108. P. 10290–10295.</mixed-citation><mixed-citation xml:lang="en">Robinson M., Tian Y., Delaney W.E. 4th, Greenstein A.E. Preexisting drug-resistance mutations reveal unique barriers to resistance for distinct antivirals // Proc. Natl Acad. Sci. USA. 2011. V. 108. P. 10290–10295.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Srivastava R., Peterson M.S., Bentley W.E. Stochastic kinetic analysis of the Escherichia coli stress circuit using σ32-targeted antisense // Biotechnol. Bioengineer. 2001, V. 75. P. 120–129.</mixed-citation><mixed-citation xml:lang="en">Srivastava R., Peterson M.S., Bentley W.E. Stochastic kinetic analysis of the Escherichia coli stress circuit using σ32-targeted antisense // Biotechnol. Bioengineer. 2001, V. 75. P. 120–129.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Stone M., Jia S., Heo W.D. et al. Participation of rab5, an early endosome protein, in hepatitis C virus RNA replication machinery // J. Virol. 2007. V. 81. P. 4551–4563.</mixed-citation><mixed-citation xml:lang="en">Stone M., Jia S., Heo W.D. et al. Participation of rab5, an early endosome protein, in hepatitis C virus RNA replication machinery // J. Virol. 2007. V. 81. P. 4551–4563.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Tang H., Grisé H. Cellular and molecular biology of HCV infection and hepatitis // Clin. Sci. (Lond.) 2009. V. 117. P. 49–65.</mixed-citation><mixed-citation xml:lang="en">Tang H., Grisé H. Cellular and molecular biology of HCV infection and hepatitis // Clin. Sci. (Lond.) 2009. V. 117. P. 49–65.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Targett-Adams P., Boulant S., McLauchlan J. Visualization of double-stranded RNA in cells supppporting hepatitis C virus RNA replication // J. Virol. 2008. V. 82. P. 2182–2195.</mixed-citation><mixed-citation xml:lang="en">Targett-Adams P., Boulant S., McLauchlan J. Visualization of double-stranded RNA in cells supppporting hepatitis C virus RNA replication // J. Virol. 2008. V. 82. P. 2182–2195.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Zoulim F., Chevallier M., Maynard M., Trepo C. Clinical consequences of hepatitis C virus infection // Rev. Med. Virol. 2003. V. 13. P. 57–68.</mixed-citation><mixed-citation xml:lang="en">Zoulim F., Chevallier M., Maynard M., Trepo C. Clinical consequences of hepatitis C virus infection // Rev. Med. Virol. 2003. V. 13. P. 57–68.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
