antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»antibiotics-329Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSЭкспериментальное изучение противовирусной активности Ингавирина® в отношении аденовируса человекаExperimental Study of Ingavirin® Antiviral Activity Against Human AdenovirusЗарубаевВ. В.ZarubaevV. V.noemail@neicon.ruСлитаА. В.SlitaA. V.noemail@neicon.ruСироткинА. К.SirotkinA. K.noemail@neicon.ruНебольсинВ. Е.NebolsinV. E.noemail@neicon.ruКиселевО. И.KiselevO. I.noemail@neicon.ruНИИ гриппа СЗО РАМН, Санкт-ПетербургРоссияResearch Institute of Influenza, North-West Branch of the Russian Academy of Medical Sciences, St.PetersburgRussian FederationОАО «Валента Фарм», МоскваРоссияValenta Farm, MoscowRussian Federation201013052020559-101924Copyright © Зарубаев В.В., Слита А.В., Сироткин А.К., Небольсин В.Е., Киселев О.И., 20202020Зарубаев В.В., Слита А.В., Сироткин А.К., Небольсин В.Е., Киселев О.И.Zarubaev V.V., Slita A.V., Sirotkin A.K., Nebolsin V.E., Kiselev O.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/329

Изучены противовирусные свойства препарата Ингавирин® в отношении респираторного вируса человека - аденовируса 5 типа при использовании культуры клеток НЕр-2. При концентрации Ингавирина® 1000, 100 и 10 мкг/мл формируется вирусное потомство с пониженной инфекционной способностью (в 250, 100 и 10 раз соответственно). Электронно-микроскопический анализ инфицированных клеток подтвердил способность Ингавирина® нарушать нормальный морфогенез аденовируса.

Antiviral properties of Ingavirin® were investigated in the Hep-2 cell culture with respect to the human respiratory tract virus (type 5 adenovirus). In concentrations of Ingavirin® of 1000, 100 and 10 mcg/ml the generated posterity showed lower infective capacity (by 250, 100 and 10 times respectivelly). The electron microscopy of the infected cells confirmed the Ingavirin® ability to disturb the adenovirus normal morphogenesis.

Ингавиринаденовирус человека 5 типапротивовирусная активностьэлектронно-микроскопический анализкультура клеток Нер-2Ingavirin®human type 5 adenovirusantiviral activityelectron microscopyHep-2 cell cultureReferencesDas А., Trousdale М. D., Ren S., Lien E. J. Inhibition of Herpes simplex virus type 1 and adenovirus type 5 by heterocyclic Schiff bases of amino-hydroxyguanidine tosylate. Antiviral Res 1999; 44: 3: 201-208.Das А., Trousdale М. D., Ren S., Lien E. J. Inhibition of Herpes simplex virus type 1 and adenovirus type 5 by heterocyclic Schiff bases of amino-hydroxyguanidine tosylate. Antiviral Res 1999; 44: 3: 201-208.De Clercq E., Sakuma T., Baba М. et al. Antiviral activity of phosphonylmethoxyalkyl derivatives of purines and pyrimidines. Аntiviral Res 1987; 8: 5-6: 261-272.De Clercq E., Sakuma T., Baba М. et al. Antiviral activity of phosphonylmethoxyalkyl derivatives of purines and pyrimidines. Аntiviral Res 1987; 8: 5-6: 261-272.Arav-Boger R., Echavarria М., Forman М. et al. Clearance of adenoviral hepatitis with ribavirin therapy in a pediatric liver transplant recipient. Pediatr Infect Dis J 2000; 19: 11: 1097-1100.Arav-Boger R., Echavarria М., Forman М. et al. Clearance of adenoviral hepatitis with ribavirin therapy in a pediatric liver transplant recipient. Pediatr Infect Dis J 2000; 19: 11: 1097-1100.Shetty А. К, Gans H. А., So S. et al. Intravenous ribavirin therapy for adenovirus pneumonia. Pediatr Pulmonol 2000; 29: 1: 69-73.Shetty А. К, Gans H. А., So S. et al. Intravenous ribavirin therapy for adenovirus pneumonia. Pediatr Pulmonol 2000; 29: 1: 69-73.Gavin P. J., Katz B. Z. Intravenous Ribavirin treatment for severe adenovirus disease in immunocompromised children. Pediatrics 2002; 110: 1 pt 1: 1-8.Gavin P. J., Katz B. Z. Intravenous Ribavirin treatment for severe adenovirus disease in immunocompromised children. Pediatrics 2002; 110: 1 pt 1: 1-8.Bordigoni P., Carret А. S., Venard V. et al. Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2001; 32: 9: 1290-1297.Bordigoni P., Carret А. S., Venard V. et al. Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2001; 32: 9: 1290-1297.La Rosa A. M., Champlin R. E., Mirza М. et al. Adenovirus infections in adult recipients of blood and marrow transplants. Clin Infect Dis 2001; 32: 6: 871-876.La Rosa A. M., Champlin R. E., Mirza М. et al. Adenovirus infections in adult recipients of blood and marrow transplants. Clin Infect Dis 2001; 32: 6: 871-876.Trousdale М. D., Goldschmidt P. L., Nobrega R. Evaluation of ganciclovir against human adenovirus type 5 infection in cell culture and cotton rat eyes. Antiviral Res 1993; 20: Suppl. 1: 48.Trousdale М. D., Goldschmidt P. L., Nobrega R. Evaluation of ganciclovir against human adenovirus type 5 infection in cell culture and cotton rat eyes. Antiviral Res 1993; 20: Suppl. 1: 48.Chen F. E., Liang R. H., Lo J. Y. et al. Treatment of adenovirus-associated haemorrhagic cystitis with ganciclovir. Bone Marrow Transplant 1997; 20: 11: 997-999.Chen F. E., Liang R. H., Lo J. Y. et al. Treatment of adenovirus-associated haemorrhagic cystitis with ganciclovir. Bone Marrow Transplant 1997; 20: 11: 997-999.Hillenkamp J., Reinhard T., Ross R. S. et al. The effect of cidofovir 1% with and without cyclosporin A 1% as а topical treatment of acute adenoviral keratoconjunctivitis: а controlled clinical pilot study. Ophtalmology 2002; 109: 5: 845-850.Hillenkamp J., Reinhard T., Ross R. S. et al. The effect of cidofovir 1% with and without cyclosporin A 1% as а topical treatment of acute adenoviral keratoconjunctivitis: а controlled clinical pilot study. Ophtalmology 2002; 109: 5: 845-850.Hoffman J. А., Shah А. J., Ross L. А., Кароor N. Adenoviral infections and а prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 7: 388-394.Hoffman J. А., Shah А. J., Ross L. А., Кароor N. Adenoviral infections and а prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 7: 388-394.Romanowski E. G., Yates К. А., Gordon Y. J. Antiviral prophylaxis with twice daily topical cidofovir protects against challenge in the adenovirus type 5/New Zealand rabbit ocular model. Antiviral Res 2001; 52: 3: 275-280.Romanowski E. G., Yates К. А., Gordon Y. J. Antiviral prophylaxis with twice daily topical cidofovir protects against challenge in the adenovirus type 5/New Zealand rabbit ocular model. Antiviral Res 2001; 52: 3: 275-280.Romanowski E. G., Gordon Y. J., Araullo-Cruz T. et al. The antiviral resistance and replication of cidofovir-resistant adenovirus variants in the New Zealand white rabbit ocular model. Invest Ophtalmol Vis Sci 2001; 42: 8: 1812-1815.Romanowski E. G., Gordon Y. J., Araullo-Cruz T. et al. The antiviral resistance and replication of cidofovir-resistant adenovirus variants in the New Zealand white rabbit ocular model. Invest Ophtalmol Vis Sci 2001; 42: 8: 1812-1815.Safrin S., Cherrington J., Joffe H. S. Cidofovir. Review of current and potential clinical uses. Adv Exp Med Biol 1999; 458: 111-120.Safrin S., Cherrington J., Joffe H. S. Cidofovir. Review of current and potential clinical uses. Adv Exp Med Biol 1999; 458: 111-120.Hitchcock M. J. M., Jaffe H. S., Martin J. C., Stagg R. J. Cidofovir, a new agent with potent anti-herpesvirus activity. Antivir Chem Chemother 1996;7: 3: 115-127.Hitchcock M. J. M., Jaffe H. S., Martin J. C., Stagg R. J. Cidofovir, a new agent with potent anti-herpesvirus activity. Antivir Chem Chemother 1996;7: 3: 115-127.Gordon Y. J., Naesens L., De Clercq E. et al. The treatment of adenoviral conjunctivitis with topical cidofovir. Cornea. 1996;15: 5: 546.Gordon Y. J., Naesens L., De Clercq E. et al. The treatment of adenoviral conjunctivitis with topical cidofovir. Cornea. 1996;15: 5: 546.Coca S., Perazella M. A. Rapid communication: acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity. Am J Med Sci 2002; 324: 6: 342-344.Coca S., Perazella M. A. Rapid communication: acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity. Am J Med Sci 2002; 324: 6: 342-344.Kaneko H., Kato К., Mori S., Shigеtа S. Antiviral activity of NMSO3 against adenovirus in vitro. Antiviral Res 2001; 52: 3: 281-288.Kaneko H., Kato К., Mori S., Shigеtа S. Antiviral activity of NMSO3 against adenovirus in vitro. Antiviral Res 2001; 52: 3: 281-288.Zarubaev V. V., Slita A. V., Krivitskaya V. Z. et al. Direct antiviral effect of cycloferon (10-carboxymethyl-9-acridanone) against adenovirus type 6 in vitro. Antiviral Res 2003; 58: 2: 131-137.Zarubaev V. V., Slita A. V., Krivitskaya V. Z. et al. Direct antiviral effect of cycloferon (10-carboxymethyl-9-acridanone) against adenovirus type 6 in vitro. Antiviral Res 2003; 58: 2: 131-137.Rautenschlein S., Miller R. L., Sharma J. M. The inhibitory effect of the imidazoquinolinamine S-28828 on the pathogenesis of a type II adenovirus in turkeys. Antiviral Res 2000; 46: 3: 195-205.Rautenschlein S., Miller R. L., Sharma J. M. The inhibitory effect of the imidazoquinolinamine S-28828 on the pathogenesis of a type II adenovirus in turkeys. Antiviral Res 2000; 46: 3: 195-205.Naesens L., Lenaerts L., Andrei G. et al. Antiadenovirus activities of several classes of nucleoside and nucleotide analogues. Antimicrob Agents Chemother 2005; 49: 1010-1016.Naesens L., Lenaerts L., Andrei G. et al. Antiadenovirus activities of several classes of nucleoside and nucleotide analogues. Antimicrob Agents Chemother 2005; 49: 1010-1016.Mentel R., Kinder М., Wegner U. et al. Inhibitory activity of 3-fluoro-2-deoxythymidine and related nucleoside analogues against adenoviruses in vitrn. Antiviral Res 1997; 34: 3: 113-119.Mentel R., Kinder М., Wegner U. et al. Inhibitory activity of 3-fluoro-2-deoxythymidine and related nucleoside analogues against adenoviruses in vitrn. Antiviral Res 1997; 34: 3: 113-119.Zarubaev V. V., Slita A. V., Sukhinin V. P. et al. Effect of 6-azacytidine on the course of experimental adenoviral infection in newborn Syrian hamsters. J Chemother 2007; 19: 1: 44-51.Zarubaev V. V., Slita A. V., Sukhinin V. P. et al. Effect of 6-azacytidine on the course of experimental adenoviral infection in newborn Syrian hamsters. J Chemother 2007; 19: 1: 44-51.Alexeeva I., Dyachenko N., Nosach L.et al. 6-Azacytidine - compound with wide spectrum of antiviral activity. Nucleosides Nucleotides Nucleic Acids. 2001; 20: 4-7: 1147-1152.Alexeeva I., Dyachenko N., Nosach L.et al. 6-Azacytidine - compound with wide spectrum of antiviral activity. Nucleosides Nucleotides Nucleic Acids. 2001; 20: 4-7: 1147-1152.Weber J. M., Ruzindana-Umunyana A., Imbeault L., Sircar S. Inhibition of adenovirus infection and adenain by green tea catechins. Antiviral Res 2003; 58: 2: 167-173.Weber J. M., Ruzindana-Umunyana A., Imbeault L., Sircar S. Inhibition of adenovirus infection and adenain by green tea catechins. Antiviral Res 2003; 58: 2: 167-173.Zhang Y., Schneider R. J. Adenovirus inhibition of cellular protein synthesis and the specific translation of late viral mRNAs. Semin Virol 1993; 4: 229-236.Zhang Y., Schneider R. J. Adenovirus inhibition of cellular protein synthesis and the specific translation of late viral mRNAs. Semin Virol 1993; 4: 229-236.Логинова С. Я., Борисевич С. В., Лыков М. В. и др. Изучение эффективности Ингавирина® in vitro в отношении «мексиканского» пандемического подтипа H1N1 вируса гриппа А, штаммы А/California/04/2009 и А/California/07/2009. Антибиотики и химиотер 2009; 3-4: 15-17.Логинова С. Я., Борисевич С. В., Лыков М. В. и др. Изучение эффективности Ингавирина® in vitro в отношении «мексиканского» пандемического подтипа H1N1 вируса гриппа А, штаммы А/California/04/2009 и А/California/07/2009. Антибиотики и химиотер 2009; 3-4: 15-17.Логинова С. Я., Борисевич С. В., Максимов В. А. и др. Изучение терапевтической эффективности нового отечественного препарата Ингавирин в отношении возбудителя гриппа А (H3N2). Там же 2008; 53: 11/12: 27-30.Логинова С. Я., Борисевич С. В., Максимов В. А. и др. Изучение терапевтической эффективности нового отечественного препарата Ингавирин в отношении возбудителя гриппа А (H3N2). Там же 2008; 53: 11/12: 27-30.Xing L., Tikoo S. K. Packaging ofviral RNAs in virions of adenoviruses. Virol J 2009; 5: 6: 16.Xing L., Tikoo S. K. Packaging ofviral RNAs in virions of adenoviruses. Virol J 2009; 5: 6: 16.Erturk E., Ostapchuk P., Wells S. I. et al. Binding of CCAAT displacement protein CDP to adenovirus packaging sequences. J Virol 2003; 77: 11: 6255-6264.Erturk E., Ostapchuk P., Wells S. I. et al. Binding of CCAAT displacement protein CDP to adenovirus packaging sequences. J Virol 2003; 77: 11: 6255-6264.Ostapchuk P., Hearing P. Regulation of adenovirus packaging. Curr Top Microbiol Immunol. 2003; 272: 165-185.Ostapchuk P., Hearing P. Regulation of adenovirus packaging. Curr Top Microbiol Immunol. 2003; 272: 165-185.Логинова С. Я., Борисевич С. В., Максимов В. А. и др. Изучение эффективности Ингавирина® in vitro в отношении возбудителя аденовирусной инфекции. Антибиотики и химиотерапия, 2009, 54; 7-8.Логинова С. Я., Борисевич С. В., Максимов В. А. и др. Изучение эффективности Ингавирина® in vitro в отношении возбудителя аденовирусной инфекции. Антибиотики и химиотерапия, 2009, 54; 7-8.

The authors declare that there are no conflicts of interest present.