antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2022-67-11-12-10-15antibiotics-989Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯEXPERIMENTAL STUDIESИзучение активности противовирусных препаратов в отношении возбудителя лихорадки Чикунгунья в культуре клетокStudy of the Activity of Antiviral Drugs Against the Causative Agent of Chikungunya Fever in Cell Culturehttps://orcid.org/0000-0001-6732-8404ЛогиноваС. Я.LoginovaS. Ya.

Логинова Светлана Яковлевна — доктор биологических наук, ведущий  научный  сотрудник.

ул. Октябрьская, д. 11, 48 Сергиев Посад-6, 141306

Svetlana Ya. Loginova — D. Sc. in Biology, leading researcher at the 48th Central Scientific Research Institute of the Ministry of Defence of the Russian  Federation.

Sergiev Posad

https://orcid.org/0000-0002-5461-3641ЩукинаВ. Н.SchukinaV. N.

Щукина Вероника Николаевна — кандидат биологических наук, научный сотрудник.

ул. Октябрьская, д. 11, 48 Сергиев Посад-6, 141306

Veronika N. Schukina — Ph.  D. in Biology, researcher  at the 48th  Central  Scientific Research  Institute  of the  Ministry  of Defence of the  Russian  Federation.

Sergiev  Posad

https://orcid.org/0000-0002-5175-916XСавенкоС. В.SavenkoS. V.

Савенко Сергей Владимирович — научный  сотрудник.

ул. Октябрьская, д. 11, 48 Сергиев Посад-6, 141306

Sergey V. Savenko — researcher  at the 48th  Central  Scientific Research  Institute  of the Ministry  of Defence of the Russian Federation.

Sergiev Posad

https://orcid.org/0000-0001-6155-1365СахаровР. В.SakharovR. V.

Сахаров Роман Владимирович — старший научный  сотрудник отдела опасных вирусных  инфекций.

ул. Октябрьская, д. 11, 48 Сергиев Посад-6, 141306

Roman V. Sakharov — Senior  researcher  at the Department of Dangerous Viral Infections, 48th Central Scientific Research Institute of the Ministry of Defence of the Russian Federation

Sergiev Posad

https://orcid.org/0000-0002-6742-3919БорисевичС. В.BorisevichS. V.

Борисевич Сергей Владимирович — доктор биологических наук, профессор, академик РАН РФ, начальник института.

ул. Октябрьская, д. 11, 48 Сергиев Посад-6, 141306

Sergey V. Borisevich — D. Sc. in Biology, professor, Academician of the  Russian  Academy  of Sciences, Head  of the  Institute, 48th  Central  Scientific Research  Institute  of the  Ministry  of Defence of the  Russian  Federation.

Sergiev Posad

48cnii@mil.ru48 Центральный НИИ Минобороны РоссииРоссия48<sup>th</sup> Central Scientific Research Institute of the Ministry of Defence of the Russian FederationRussian Federation2022110220236711-121015Copyright &#x00A9; Логинова С.Я., Щукина В.Н., Савенко С.В., Сахаров Р.В., Борисевич С.В., 20232023Логинова С.Я., Щукина В.Н., Савенко С.В., Сахаров Р.В., Борисевич С.В.Loginova S.Y., Schukina V.N., Savenko S.V., Sakharov R.V., Borisevich S.V.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/989

Вирус Чикунгунья является  представителем вирусов рода Flavivirus, семейства Flaviviridae, и относится  к зоонозным арбовирусным инфекциям, переносимым комарами рода Aedes.В организме человека этот флавивирус вызывает  заболевание, известное как лихорадка чикунгунья, этиологически  родственное жёлтой лихорадке, лихорадкам денге, Западного  Нила и Зика.  Специфического лечения лихорадки чикунгунья  нет, вакцина или же химиопрепараты на сегодняшний день также отсутствуют. Проведённый сравнительный анализ эффективности химиопрепаратов, индукторов интерферона и двух классов интерферона α-, β-, и γ- показал, что препараты интерферона  эффективно подавляют репродукцию вируса в культуре клеток Vero в широком  диапазоне концентраций. Химиопрепараты Триазавирин®, Триазид®  и Ингавирин® не влияли на репродукцию вируса Чикунгунья, штамм FN198/66, в культуре клеток Vero.Рибавирин® в концентрации 100 мкг/мл практически полностью подавлял репродукцию вируса Чикунгунья при внесении препарата в культуральную среду как до, так и после инфицирования.

Сhikungunya  virus (CHIKV) is a member of the Flavivirus genus, Flaviviridae family. It belongs to the zoonotic arbovirus infections transmitted by mosquitoes of the genus Aedes. In humans, this flavivirus causes a disease known as Сhikungunya fever, etymologically related to yellow fever, dengue, West Nile, and Zika. There is no specific treatment for Сhikungunya fever, as there is no vaccine or preventive measures to date. A comparative analysis of the effectiveness of chemotherapy drugs, interferon inducers and two classes of interferon α-, β-, and γ-showed that interferon drugs effectively inhibit the reproduction of CHIKV in the Vero cell culture in a wide range of concentrations. Chemotherapy drugs Triazavirin® and Ingavirin®  did not affect the reproduction of CHIKV strain FN198/66 in Vero cell culture. Ribavirin® at a concentration of 100 µg/ml almost completely suppressed the reproduction of the CHIKV virus when the drug was introduced into the culture medium both before and after infection.

вирус ЧикунгуньяТриазавирин®Рибавирин®Ингавирин®Реаферон-ЕС®Rebif (β1a)®противовирусная эффективностькультура клетокСhikungunya virusTriazavirin®Ribavirin®Ingavirin®Reaferon-EU®Rebif (β1a)®antiviral efficacycell cultureReferencesWang Y. M., W J. Lu, Lin C.C. et al. Antiviral activities of niclosamide and nitazoxanide against chikungunya virus entry and transmission. Antiviral Res. 2016; 135: 81–90. doi: 10.1016/j.antiviral.2016.10.003.Wang Y. M., W J. Lu, Lin C.C. et al. Antiviral activities of niclosamide and nitazoxanide against chikungunya virus entry and transmission. Antiviral Res. 2016; 135: 81–90. doi: 10.1016/j.antiviral.2016.10.003.Delang L., Li C., Tas A., Quérat G. et al. The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection. Sci Rep. 2016; 6: 31819. doi: 10.1038/srep31819.Delang L., Li C., Tas A., Quérat G. et al. The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection. Sci Rep. 2016; 6: 31819. doi: 10.1038/srep31819.Ching K.C., Kam Y.W., Merits A. et al. Trisubstituted thieno[3,2-b]pyrrole 5-carboxamides as potent inhibitors of alphaviruses. J Med Chem. 2015; 58 (23): 9196–9213. doi: 10.1021/acs.jmedchem.5b01047.Ching K.C., Kam Y.W., Merits A. et al. Trisubstituted thieno[3,2-b]pyrrole 5-carboxamides as potent inhibitors of alphaviruses. J Med Chem. 2015; 58 (23): 9196–9213. doi: 10.1021/acs.jmedchem.5b01047.Lani R., Hassandarvish P., Shu M.-H. et al. Antiviral activity of selected flavonoids against Chikungunya virus. Antivir Res. 2016; 133: 50–61. doi: 10.1016/j.antiviral.2016.07.009.Lani R., Hassandarvish P., Shu M.-H. et al. Antiviral activity of selected flavonoids against Chikungunya virus. Antivir Res. 2016; 133: 50–61. doi: 10.1016/j.antiviral.2016.07.009.Albulescu I.C., van Hoolwerff M., Wolters L.A. et al. Suramin inhibits chikungunya virus replication through multiple mechanisms. Antivir Res. 2015; 121: 39–46. doi: 10.1016/j.antiviral.2015.06.013.Albulescu I.C., van Hoolwerff M., Wolters L.A. et al. Suramin inhibits chikungunya virus replication through multiple mechanisms. Antivir Res. 2015; 121: 39–46. doi: 10.1016/j.antiviral.2015.06.013.Staveness D., Abdelnabi R., Near K. E. et al. Inhibition of Chikungunya virus-induced cell death by salicylate-derived bryostatin analogues provides additional evidence for a PKC-independent pathway. J Nat Prod. 2016; 79 (4): 680–684. doi: 10.1021/acs.jnatprod.5b01017.Staveness D., Abdelnabi R., Near K. E. et al. Inhibition of Chikungunya virus-induced cell death by salicylate-derived bryostatin analogues provides additional evidence for a PKC-independent pathway. J Nat Prod. 2016; 79 (4): 680–684. doi: 10.1021/acs.jnatprod.5b01017.Mishra P., Kumar A., Mamidi P. et al. Inhibition of chikungunya virus replication by 1-[(2-Methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea(MBZM-N-IBT). Sci Rep. 2016; 6: 20122.Mishra P., Kumar A., Mamidi P. et al. Inhibition of chikungunya virus replication by 1-[(2-Methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea(MBZM-N-IBT). Sci Rep. 2016; 6: 20122.Varghese F.S., Thaa B., Amrun S.N. et al. The antiviral alkaloid berberine reduces chikungunya virus-induced mitogen-activated protein kinase signaling. J Virol. 2016; 90: 9743–9757. doi: 10.1128/JVI.01382-16.Varghese F.S., Thaa B., Amrun S.N. et al. The antiviral alkaloid berberine reduces chikungunya virus-induced mitogen-activated protein kinase signaling. J Virol. 2016; 90: 9743–9757. doi: 10.1128/JVI.01382-16.Preston S.L., Drusano G.L., Glue P. et al. Pharmacokinetics and absolute bioavailability of ribavirin in healthy volunteers as determined by stable-isotope methodology. Antimicrob Agents Chemother. 1999; 43: 2451–2456. doi: 10.1128/AAC.43.10.2451.Preston S.L., Drusano G.L., Glue P. et al. Pharmacokinetics and absolute bioavailability of ribavirin in healthy volunteers as determined by stable-isotope methodology. Antimicrob Agents Chemother. 1999; 43: 2451–2456. doi: 10.1128/AAC.43.10.2451.Food and Drug Administration (FDA). Interferon alfa-2a (Roferon-A) product approval information. Solution for injection — vials. 3/14/2003 ed Nutley, NJ: FDA, 2003; 12.Food and Drug Administration (FDA). Interferon alfa-2a (Roferon-A) product approval information. Solution for injection — vials. 3/14/2003 ed Nutley, NJ: FDA, 2003; 12.Gallegos K.M., Drusano G.L., D Argenio D.Z., Brown A.N. Chikungunya virus: in vitro response to combination therapy with ribavirin and interferon Alfa 2a. J Infect Dis. 2016; 214 (8): 1192–1197. doi: 10.1093/infdis/jiw358.Gallegos K.M., Drusano G.L., D Argenio D.Z., Brown A.N. Chikungunya virus: in vitro response to combination therapy with ribavirin and interferon Alfa 2a. J Infect Dis. 2016; 214 (8): 1192–1197. doi: 10.1093/infdis/jiw358.Scagnolari C., Caputo B., Rezza G, Antonelli G. Antiviral activity of the combination of interferon and ribavirin against Chikungunya virus: are the results conclusive? J Infect Dis. 2017; 215 (3): 492–493. doi: 10.1093/infdis/jiw579.Scagnolari C., Caputo B., Rezza G, Antonelli G. Antiviral activity of the combination of interferon and ribavirin against Chikungunya virus: are the results conclusive? J Infect Dis. 2017; 215 (3): 492–493. doi: 10.1093/infdis/jiw579.Delang L., Segura Guerrero N., Tas A. et al. Mutations in the Сhikungunya virus non-structural proteins cause resistance to favipiravir (T-705), a broad-spectrum antiviral. J Antimicrob Chemother. 2014; 69 (10): 2770–2784. doi: 10.1093/jac/dku209.Delang L., Segura Guerrero N., Tas A. et al. Mutations in the Сhikungunya virus non-structural proteins cause resistance to favipiravir (T-705), a broad-spectrum antiviral. J Antimicrob Chemother. 2014; 69 (10): 2770–2784. doi: 10.1093/jac/dku209.Kaur P., Thiruchelvan M., Lee R.C.H. et al. Inhibition of Chikungunya virus replication by Harringtonine, a novel antiviral that suppresses viral protein expression. Antimicrob Agents Chemother. 2013; 57 (1): 155. doi: 10.1128/AAC.01467-12.Kaur P., Thiruchelvan M., Lee R.C.H. et al. Inhibition of Chikungunya virus replication by Harringtonine, a novel antiviral that suppresses viral protein expression. Antimicrob Agents Chemother. 2013; 57 (1): 155. doi: 10.1128/AAC.01467-12.Руководство по проведению доклинических исследований лекарственных средств. Часть 1, М.: Минздрав РФ, 2013; 942.Rukovodstvo po provedenijyu doklinicheskikh issledovanij lekarstvennykh sredstv. Chast' 1, Moscow: Minzdrav RF, 2013; 942. (in Russian)Ашмарин И.П., Воробьев А.А. Статистические методы в микробиологических исследованиях. Ленинград: Медгиз., 1962; 180.Ashmarin I.P., Vorob'ev A.A. Statisticheskie metody v mikrobiologicheskikh issledovaniyakh. Leningrad: Medgiz., 1962; 180. (in Russian)Ravichandran R., Manian M. Ribavirin therapy for Chikungunya arthritis. J Infect Developing Countries. 2008; 2 (2): 140–142.Ravichandran R., Manian M. Ribavirin therapy for Chikungunya arthritis. J Infect Developing Countries. 2008; 2 (2): 140–142.

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