Email this article THE STUDY OF TOXICITY AND THE PROTECTIVE PROPERTIES OF IFN-A2B WITH ANTIOXIDANTS AND SPECIFIC ANTIVIRAL CHEMO DRUGS FOR HERPES VIRAL INFECTIONS "IN VITRO" AND "IN VIVO"
- Authors: Vasiliev A.N.1, Klimova R.R.2, Tyulenev Y.A.2
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Affiliations:
- Center for examination and control of proprietary medicines, Federal State Institution National Research Center for Medicinal Products Quality Control of Ministry of Public Health and Social Development
- Federal State Budget-Financed Institution “D. I. Ivanovsky Institute of Virology”
- Issue: Vol 17, No 2 (2012)
- Pages: 29-35
- Section: Articles
- URL: https://journal-vniispk.ru/1560-9529/article/view/40649
- DOI: https://doi.org/10.17816/EID40649
- ID: 40649
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Abstract
Herpes simplex virus-1 (HSV1) and cytomegalovirus (CMV) are extremely widespread in the human population and can affect various organs and tissues. HSV1 and CMV infections are particularly dangerous for pregnant women and newborns. The main disadvantages of antiviral chemotherapeutic agents are their high toxicity, limited bioavailability and the development of drug resistance during the long-term tretatment. Currently the search for new drugs and new regimens which permit to avoid the adverse manifestations of toxic effects while maintenance of high antiviral efficacy is performed. The purpose of this study was to evaluate the effectiveness of the of scheme of multimodal therapy of herpes virus infection with a new drug form (NDF) VIFERON®, a solution for local application in combination with specific antiviral chemo drugs "in vitro" and "in vivo". For the first time the use of NDF in a concentration of 20000 IU/ml was found to inhibit CMV infection by 83% in a therapeutic scheme “in vitro”. NDF has been shown to increase the specific antiviral activity of chemotherapy, allowing to significantly reduce the effective inhibitory concentration for Acyclovir - by 3 times, for Acyclovir - by 20 times. In “in vivo” experiments NDF has not demonstrated any toxic effect on the animal organism. 24 h after intraperitoneal infection of mice HSV1 the single administration of NDF protects 60% of the animals from lethal (20 LD5o) herpes virus infection. Combined use of ТДА and ACV therapeutic scheme “in vivo” allowed: a) reduce the dose of both drugs by 10 times (up to 2000 IU/ml and 5 mg/kg, respectively) compared with either single agent; and b) to achieve the therapeutic effect with the use of the short regimen - 3 days; c) to provide full protection (100%) animals from lethal HSV1-infection (20 LD50). The high protective effect of multimodal therapy of lethal herpes virus infection “in vivo” was provided due to the synergistic character of the interaction of drugs used.
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##article.viewOnOriginalSite##About the authors
A. N. Vasiliev
Center for examination and control of proprietary medicines, Federal State Institution National Research Center for Medicinal Products Quality Control of Ministry of Public Health and Social Developmentканд. биол. наук, дир. Центра экспертизы и контроля готовых лекарственных средств России ФГБУ Научный центр экспертизы средств медицинского применения Минздравсоцразвития России
R. R. Klimova
Federal State Budget-Financed Institution “D. I. Ivanovsky Institute of Virology”канд. биол. наук, ст. науч. сотр. ФГБУ Научно-исследовательский институт вирусологии им. Д. И. Ивановского Минздравсоцразвития России
Yu. A. Tyulenev
Federal State Budget-Financed Institution “D. I. Ivanovsky Institute of Virology”мл. науч. сотр. ФГБУ Научно-исследовательский институт вирусологии им. Д. И. Ивановского Минздравсоцразвития России
References
- Выжлова Е. Н., Андронова В. Л., Галегов Г. А., Малиновская В. В. Комбинированное антигерпесвирусное действие комплексного препарата “Виферон - капли глазные” и модифицированных нуклеозидов // Бюл. экспер. биол. - 2006. - Т. 141, № 6. - С. 672-676.
- Выжлова Е. Н. Антивирусная активность новой лекарственной формы интерферона для местного применения: Автореф. дис.. канд. биол. наук. - М., 2008.
- Климова Р. Р., Масалова О. В., Атанадзе С. Н. и др. Получение и свойства моноклональных антител к вирусу герпеса 1-го и 2-го типа // Журн. микробиол. - 1999. - № 5. - С. 99-103.
- Макарова Н., Кущ А., Иванова Л. и др. Получение моноклональных антител к сверхранним белкам цитомегаловируса человека и их применение для выявления инфицированных клеток // Вопр. вирусол. - 1996. - № 1. - С. 28-32.
- Farley N., Bernstein D. I., Bravo F. J. et al. Recurrent vaginal shedding of herpes simplex type 2 virus in the mouse and effects of antiviral therapy // Antiviral Res. - 2010. - Vol. 86, N 2. - P. 188-195.
- Field H. J., Biswas S. Antiviral drug resistance and helicase-primase inhibitors of herpes simplex virus // Drug Resist. Updat. - 2010. - [Epub ahead of print].
- Gebhardt B. M., Focher F., Eberle R. et al. Effect of combinations of antiviral drugs on herpes simplex encephalitis // Drug Des. Devel. Ther. - 2009. - Vol. 3. - P. 289-294.
- Khetsuriani N., Holman R. C., Anderson L. J. Burden of encephalitis-associated hospitalizations in the United States, 1988-1997 // Clin. Infect. Dis. - 2002. - Vol. 35. - P. 175-182.
- Kimberlin D. W. Management of HSV encephalitis in adults and neonates: diagnosis, prognosis and treatment // Herpes. - 2007. -Vol. 14. - N 1. - P. 11-16.
- Lampi G., Deidda D., Pinza M. et al. Enhancement of anti-herpetic activity of glycyrrhizic acid by physiological proteins // Antiviral Chem. Chemother. - 2001. - Vol. 12, N 2. - P. 125-131.
- Lischka P., Zimmermann H. Antiviral strategies to combat cytomegalovirus infections in transplant recipients // Curr. Opin. Pharmacol. - 2008. - Vol. 8, N 5. - P. 541-548.
- Lischka P., Hewlett G., Wunberg T. et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246 // Antimicrob. Agents Chemother. - 2010. - Vol. 54, N 3. - P. 1290-1297.
- Michaels M. G. Treatment of congenital cytomegalovirus: where are we now? // Expert. Rev. Antiinfect. Ther. - 2007. - Vol. 5, N 3. - P. 441-448.
- Naesens L., De Clercq E. Recent developments in herpesvirus therapy // Herpes. - 2001. - Vol. 8, N 1. - P. 12-16.
- Scott H. J., Kimberlin D. W., Whitley R. J. Antiviral therapy for herpesvirus central nervous system infections: Neonatal herpes simplex virus infection, herpes simplex encephalitis, and congenital cytomegalovirus infection // Antiviral Res. - 2009. - Vol. 83, N 3. - P. 207-213.
- Smith J. D., De Harven E. Herpes simplex virus and human cytomegalovirus replication in WI-38 cells. I. Sequence of viral replica tion // J. Virol. - 1973. - Vol. 12, N 4. - P. 919-930.
- Spector T., Harrington J. A., Morrison R. W. et al. 2-Acetylpyridine 5-[(dimethylamino)thiocarbonyl]-thiocarbonohydrazone (A1110U), a potent inactivator of ribonucleotide reductases of herpes simplex and varicella-zoster viruses and a potentiator of acyclovir // Proc. Natl Acad. Sci. USA. - 1989. - Vol. 86, N 3. - P. 1051-1055.
- Vyzhlova E. N., Andronova V. L., Galegov G. A., Malinovskaya V. V. Synergistic antiherpesviral combination of alpha interferon and nucleoside analog or pyrophosphate analog in relation to herpes simplex virus in cell culture in vitro // J. Interferon Cytokine Res. - 2007. - Vol. 27, N 8. - P. 737-738.
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