Study on Antiviral Activity and Pharmacological Safety of Double-Stranded Ribonucleic Acid for Intranasal Administration
https://doi.org/10.37489/0235-2990-2022-67-9-10-42-48
Abstract
Interferon inducers are of interest as the first line of defense against viral infections, including influenza. Double-stranded ribonucleic acid (dsRNA) for intranasal administration has been developed, the excipients and drug components were selected at the Institute of Medical Biotechnology, a branch of the State Research Center of Virology and Biotechnology «Vector». This work presents the results of the study on antiviral activity and pharmacological safety of a new form of dsRNA. The antiviral activity of the preparation was studied in BALB/c mice infected with influenza A/Aichi/2/68 (H3N2) or Bishkek/01/2009 (H1N1pdm09) viruses. A safety study was performed with a single administration of intranasal dsRNA into white outbred ICR mice. The study showed that the administration of therapeutic and prophylactic regimen of intranasal dsRNA at a dose of 2.5 mg/kg increases the survival and average life expectancy of mice infected with the mentioned strains of influenza virus. The protective effect of the preparation in mice infected with a lethal dose of Bishkek/01/2009 virus was comparable to the effect of Tamiflu. The absence of toxic effects of intranasal dsRNA at a pharmacological dose in laboratory mice, the functional state of their physiological systems, as well as main types of metabolism, established in the experiments, lead to a conclusion concerning pharmacological safety of the preparation and the prospects for further work to complete pharmaceutical development of a new antiviral drug.
About the Authors
S. G. GamaleyRussian Federation
Svetlana G. Gamaley — Head of the Department of Biological Studies
ResearcherID: B-7418-2014
eLIBRARY SPIN-код: 6593-3420
Scopus Author ID: 6504003751
Koltsovo, Novosibirsk Region
G. G. Shimina
Russian Federation
Galina G. Shimina — Researcher at the Department of Biological Studies
Koltsovo, Novosibirsk Region
E. S. Tsyplenkova
Russian Federation
Elena S. Tsyplenkova — Junior researcher at the Department of Biological Studies
Koltsovo, Novosibirsk Region
O. V. Simakova
Russian Federation
Olga V. Simakova — Junior researcher at the Department of Biological Studies
Koltsovo, Novosibirsk Region
M. O. Skarnovich
Russian Federation
Maxim O. Skarnovich — M. D., Senior researcher at the Department of Extremely Hazardous Virus Infections Prevention and Treatment
eLIBRARY SPIN-код: 8405-5175
Scopus Author ID: 57189059427
Koltsovo, Novosibirsk Region
M. A. Skarnovich
Russian Federation
Maria A. Skarnovich — Researcher at the Department of Extremely Hazardous Virus Infections Prevention and Treatment
eLIBRARY SPIN-код: 6381-5817
Scopus Author ID: 57189059427
Koltsovo, Novosibirsk Region
L. N. Shishkina
Russian Federation
Larisa N. Shishkina — D. Sc. in Biology, Head of the Department of Extremely Hazardous Virus Infections Prevention and Treatment
ResearcherID: B-2263-2014
eLIBRARY SPIN-код: 7165-4367
Scopus Author ID: 35316454500
Koltsovo, Novosibirsk Region
O. S. Taranov
Russian Federation
Oleg S. Taranov — Head of the Department of Microscopy
ResearcherID: A-5657-2014
eLIBRARY SPIN-код: 5894-6518
Scopus Author ID: 8938697800
Koltsovo, Novosibirsk Region
O. S. Ivanova
Russian Federation
Olga S. Ivanova — Ph. D. in Biology, Researcher at the Department of Technology Development and Pilot Production of Biologicals
eLIBRARY SPIN-код: 4165-6310
Koltsovo, Novosibirsk Region
G. M. Levagina
Russian Federation
Galina M. Levagina — Ph. D. in Biology, Head of the Department of Technology Development and Pilot Production of Biologicals
ResearcherID: C-7590-2014
eLIBRARY SPIN-код: 6837-4940
Scopus Author ID: 6506245503
Koltsovo, Novosibirsk Region
E. D. Danilenko
Russian Federation
Elena D. Danilenko — Ph. D. in Biology, Director of the Institute of Medical Biotechnology
ResearcherID: A-7083-2014
eLIBRARY SPINкод: 1388-4127
Scopus Author ID: 7004245682
Koltsovo, Novosibirsk Region
References
1. Даниленко Е.Д., Белкина А.О., Сысоева Г.М. Создание лекарственных препаратов на основе высокополимерных двуспиральных РНК для противовирусной и противоопухолевой терапии. Биомедицинская химия. 2019; 65 (4): 277–293. https://doi.org/10.18097/PBMC20196504277. [Danilenko E.D., Belkina A.O., Sysoeva G. M. Development of drugs on the basis of high-polymeric double-stranded RNA for antiviral and antitumor therapy. Biomeditsinskaya Khimiya. 2019; 65 (4): 277–293. https://doi.org/10.18097/PBMC20196504277. (in Russian)]
2. Иванова О.С., Левагина Г.М., Скарнович М.О., Скарнович М.А., Шишкина Л.Н., Гамалей С.Г., Даниленко Е.Д. Получение и характеристика препарата двуспиральной РНК из дрожжей Saccharomyces cerevisiae для интраназального применения. Биофармацевтический журнал. 2019; 11 (4): 29–33. [Ivanova O.S., Levagina G.M., Skarnovich M.O., Skarnovich M.A., Shishkina L.N., Gamaley S.G., Danilenko E.D. Obtaining and characterization of double stranded RNA preparation from Saccoromyces cerevisiae yeast for intranasal application. Biofarmatsevticheskii Zhurnal. 2019; 11 (4): 29–33. (in Russian)]
3. Руководство по содержанию и использованию лабораторных животных. / Под ред. Белозерцевой И.В., Блинова Д.В., Красильщиковой М.С. Восьмое издание. пер. с англ. — М.: ИРБИС; 2017. [Guide for the care and use of laboratory animals. 8th. ed. Belozerceva I.V., Blinov D.V., Krasil'shhikova M.S., eds. Moscow: Irbis; 2017. (in Russian)]
4. Директива 2010/63/EU Европейского парламента и совета европейского союза по охране животных, используемых в научных целях. Пер. с англ. RusLasa. — С-ПБ; 2012. [Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Translated by RusLasa. — S-PB; 2012.] Доступно по: https://ruslasa.ru/wp-content/uploads/2017/06/Directive_201063_rus.pdf. Ссылка активна на 20.07.2022.
5. ГОСТ 33215-2014 Руководство по содержанию и уходу за лабораторными животными. Правила оборудования помещений и организации процедур; ГОСТ 33216-2014 Руководство по содержанию и уходу за лабораторными животными. Правила содержания и ухода за лабораторными грызунами и кроликами. [GOST 33215-2014 Rukovodstvo po soderzhaniyu i ukhodu za laboratornymi zhivotnymi. Pravila oborudovaniya pomeshchenii i organizatsii protsedur; GOST 33216-2014 Rukovodstvo po soderzhaniyu i ukhodu za laboratornymi zhivotnymi. Pravila soderzhaniya i ukhoda za laboratornymi gryzunami i krolikami. (in Russian)]
6. Новицкий В.В., Евтушенко О.М. Руководство к практическим занятиям по гематологии. Томск; 1999. [Novitskiy V.V., Evtushenko O.M. Rukovodstvo k prakticheskim zanyatiyam po gematologii. Tomsk; 1999. (in Russian)]
Review
For citations:
Gamaley S.G., Shimina G.G., Tsyplenkova E.S., Simakova O.V., Skarnovich M.O., Skarnovich M.A., Shishkina L.N., Taranov O.S., Ivanova O.S., Levagina G.M., Danilenko E.D. Study on Antiviral Activity and Pharmacological Safety of Double-Stranded Ribonucleic Acid for Intranasal Administration. Antibiot Khimioter = Antibiotics and Chemotherapy. 2022;67(9-10):42-48. (In Russ.) https://doi.org/10.37489/0235-2990-2022-67-9-10-42-48