{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:54:54Z","timestamp":1779922494688,"version":"3.53.1"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Free radical reactions play an important role in biological functions of living systems. The balance between oxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Experimental works demonstrate the role of oxidative stress that is caused by influenza virus as well as the toxic effects of some antiviral drugs. Therefore, antiviral drugs should be characterized by its pro- and antioxidant activity, because it can affect its therapeutic efficiency. The aim of the study was to quantify the antioxidant capacity and propose the mechanism of the antioxidant effect of the antiviral drug Umifenovir (Arbidol\u00ae). The kinetic chemiluminescence with the 2,2\u2019-azobis (2-amidinopropane) dihydrochloride + luminol system was used to quantify the antioxidant capacity of Umifenovir relative to the standard compound Trolox. With computer simulation, the reaction scheme and rate constants were proposed. The antioxidant capacity of 0.9 \u03bcM Umifenovir (maximum concentration of Umifenovir in blood after oral administration of 200 mg) was as high as 1.65 \u00b1 0.18 \u03bcM of Trolox. Thus, the total antioxidant capacity of Umifenovir is comparable to the antioxidant capacity of Trolox. Unlike Trolox, Umifenovir reacts with free radicals in two stages. For Trolox, the free radical scavenging rate constant was k = 2000 nM\u22121 min.\u22121, for Umifenovir k1 = 300 nM\u22121min.\u22121, k2 = 4 nM\u22121min.\u22121. Slower kinetics of Umifenovir provides the prolonged antioxidant effect when compared to Trolox. This phenomenon can make a serious contribution to the compensation of oxidative stress that is caused by a viral disease and the therapeutic effect of the drug.<\/jats:p>","DOI":"10.3390\/molecules25071577","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T05:55:16Z","timestamp":1585893316000},"page":"1577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Antioxidant Potential of Antiviral Drug Umifenovir"],"prefix":"10.3390","volume":"25","author":[{"given":"Elena V.","family":"Proskurnina","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, ul. Moskvorechye 1, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry Yu.","family":"Izmailov","sequence":"additional","affiliation":[{"name":"Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky prospekt 27-1, Moscow 119234, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madina M.","family":"Sozarukova","sequence":"additional","affiliation":[{"name":"Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninsky prospekt 31, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana A.","family":"Zhuravleva","sequence":"additional","affiliation":[{"name":"Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky prospekt 27-1, Moscow 119234, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina A.","family":"Leneva","sequence":"additional","affiliation":[{"name":"Department of Experimental Virology, Mechnikov Research Institute for Vaccines and Sera, Malyi Kazennyi pereulok 5a, Moscow 105064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2004-3935","authenticated-orcid":false,"given":"Artem A.","family":"Poromov","sequence":"additional","affiliation":[{"name":"Department of Experimental Virology, Mechnikov Research Institute for Vaccines and Sera, Malyi Kazennyi pereulok 5a, Moscow 105064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.micinf.2017.08.008","article-title":"The role of oxidative stress in influenza virus infection","volume":"19","author":"Liu","year":"2017","journal-title":"Microbes Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1038\/s41598-017-05808-w","article-title":"LR-mediated antiviral innate immunity requires oxidative phosphorylation activity","volume":"7","author":"Yoshizumi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1179\/174329210X12650506623564","article-title":"Hyperglycemia, oxidative and nitrosative stress affect antiviral, inflammatory and apoptotic signaling of cultured thymocytes","volume":"15","author":"Kocic","year":"2010","journal-title":"Redox. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.mrgentox.2012.12.012","article-title":"Evaluation of the role of the antioxidant silymarin in modulating the in vivo genotoxicity of the antiviral drug ribavirin in mice","volume":"752","author":"Noshy","year":"2013","journal-title":"Mutat. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2011.10.011","article-title":"Identification of an antioxidant small-molecule with broad-spectrum antiviral activity","volume":"93","author":"Panchal","year":"2012","journal-title":"Antiviral. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0278-6915(96)00004-X","article-title":"An evaluation of the antioxidant and antiviral action of extracts of rosemary and Provencal herbs","volume":"34","author":"Aruoma","year":"1996","journal-title":"Food Chem. Toxicol."},{"key":"ref_7","first-page":"656","article-title":"Antioxidant and antiviral activities of Euphorbia thymifolia L.","volume":"9","author":"Lin","year":"2002","journal-title":"J. Biomed. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1055\/s-2002-32547","article-title":"Antiviral and antioxidant activity of flavonoids and proanthocyanidins from Crataegus sinaica","volume":"68","author":"Shahat","year":"2002","journal-title":"Planta Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1007\/s10068-017-0217-9","article-title":"In vitro antiviral, anti-inflammatory, and antioxidant activities of the ethanol extract of Mentha piperita L.","volume":"26","author":"Li","year":"2017","journal-title":"Food Sci. Biotechnol."},{"key":"ref_10","first-page":"20","article-title":"Antioxidant impact on specific antiviral activity of human recombinant interferon alpha-2b with respect to Herpes simplex in cell culture","volume":"55","year":"2010","journal-title":"Antibiot. Khimioter."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fedoreyev, S.A., Krylova, N.V., Mishchenko, N.P., Vasileva, E.A., Pislyagin, E.A., Iunikhina, O.V., Lavrov, V.F., Svitich, O.A., Ebralidze, L.K., and Leonova, G.N. (2018). Antiviral and Antioxidant Properties of Echinochrome A. Mar. Drugs, 16.","DOI":"10.3390\/md16120509"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.antiviral.2018.07.023","article-title":"Antiviral activity of silymarin against Mayaro virus and protective effect in virus-induced oxidative stress","volume":"158","author":"Camini","year":"2018","journal-title":"Antiviral. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1126\/science.2543070","article-title":"Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD","volume":"244","author":"Oda","year":"1989","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1146\/annurev.pathmechdis.3.121806.154316","article-title":"The pathology of influenza virus infection","volume":"3","author":"Taubenberger","year":"2008","journal-title":"Ann. Rev. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.clinthera.2009.04.016","article-title":"Pharmacokinetic properties and bioequivalence of two formulations of arbidol: An open-label, single-dose, randomized-sequence, two-period crossover study in healthy Chinese male volunteers","volume":"31","author":"Liu","year":"2009","journal-title":"Clin. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.antiviral.2008.10.009","article-title":"Characteristics of arbidol-resistant mutants of influenza virus: Implications for the mechanism of anti-influenza action of arbidol","volume":"81","author":"Leneva","year":"2009","journal-title":"Antivir. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/jmv.22234","article-title":"Antiviral activity of arbidol, a broad-spectrum drug for use against respiratory viruses, varies according to test conditions","volume":"84","author":"Brooks","year":"2012","journal-title":"J. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"88","DOI":"10.17116\/terarkh201587188-96","article-title":"Clinical efficacy of arbidol (umifenovir) in the therapy of influenza in adults: Preliminary results of the multicenter double-blind randomized placebo-controlled study ARBITR","volume":"87","author":"Kiselev","year":"2015","journal-title":"Terapevticheskii Arkhiv"},{"key":"ref_19","first-page":"19","article-title":"Study of the antiviral activity of domestic anti-influenza chemotherapy in cell culture and animal models","volume":"55","author":"Leneva","year":"2010","journal-title":"Voprosy Virusologii"},{"key":"ref_20","first-page":"17","article-title":"Umifenovir (Arbidol) efficacy in experimental mixed viral and bacterial pneumonia of mice","volume":"59","author":"Leneva","year":"2014","journal-title":"Antibiot. Khimioter."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Haviernik, J., Stefanik, M., Fojtikova, M., Kali, S., Tordo, N., Rudolf, I., Hubalek, Z., Eyer, L., and Ruzek, D. (2018). Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses. Viruses, 10.","DOI":"10.20944\/preprints201802.0134.v1"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/jmv.25358","article-title":"Umifenovir susceptibility monitoring and characterization of influenza viruses isolated during ARBITR clinical study","volume":"91","author":"Leneva","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_23","first-page":"9","article-title":"Antiviral activity of arbidol and its derivatives against the pathogen of severe acute respiratory syndrome in the cell cultures","volume":"53","author":"Khamitov","year":"2008","journal-title":"Voprosy Virusologii"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"56","DOI":"10.26442\/00403660.2019.03.000127","article-title":"Clinical efficacy of umifenovir in influenza and ARVI (study ARBITR)","volume":"91","author":"Pshenichnaya","year":"2019","journal-title":"Terapevticheskii Arkhiv"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.17116\/terarkh201789162-71","article-title":"Pharmacoepidemiological study of influenza and other acute respiratory viral infections in risk groups","volume":"89","author":"Bulgakova","year":"2017","journal-title":"Terapevticheskii Arkhiv"},{"key":"ref_26","unstructured":"Kubar, O.I., Stepanova, L.A., and Safonova, L.S. (1997). IV Russian National Congress \u201cMan and Medicine\u201d. VIDOX LLC."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.intimp.2018.09.043","article-title":"The antiviral activity of arbidol hydrochloride against herpes simplex virus type II (HSV-2) in a mouse model of vaginitis","volume":"68","author":"Du","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_28","first-page":"36","article-title":"Mechanisms of arbidole\u2019s immunomodulating action","volume":"3","author":"Glushkov","year":"1999","journal-title":"Vestnik Rossiiskoi Akademii Meditsinskikh Nauk"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Huang, L., Zhang, L., Liu, Y., Luo, R., Zeng, L., Telegina, I., and Vlassov, V.V. (2015). Arbidol for preventing and treating influenza in adults and children. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD011489"},{"key":"ref_30","first-page":"326","article-title":"Antioxidant properties of arbidol and its structural analogs","volume":"45","author":"Liubitskii","year":"1999","journal-title":"Voprosy Meditsinskoi Khimii"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0891-5849(94)00117-3","article-title":"Evaluation of total antioxidant potential (TRAP) and total antioxidant reactivity from luminol-enhanced chemiluminescence measurements","volume":"18","author":"Lissi","year":"1995","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","first-page":"419","article-title":"Photochemiluminescent study of the antioxidant activity in biological systems. Mathematical modeling","volume":"46","author":"Magin","year":"2000","journal-title":"Voprosy Meditsinskoi Khimii"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1134\/S0006350911060200","article-title":"Kinetic chemiluminescence as a method for study of free radical reactions","volume":"56","author":"Vladimirov","year":"2011","journal-title":"Biophysics (Moscow)"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3103\/S0027131412030029","article-title":"Determination of Antioxidants by Sensitized Chemiluminescence Using 2,2\u2019_azo_bis(2_amidinopropane)","volume":"67","author":"Alekseev","year":"2012","journal-title":"Mosc. Univ. Chem. Bull."},{"key":"ref_35","first-page":"70","article-title":"Determination of antioxidant activity by measuring the chemiluminescence kinetics","volume":"7","author":"Izmailov","year":"2011","journal-title":"Fotobiologiya I Fotomeditsina"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1016\/S0021-9258(18)89536-9","article-title":"Effect of phytyl side chain of vitamin E on its antioxidant activity","volume":"260","author":"Niki","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/0891-5849(95)00022-P","article-title":"Plant defense metabolism is increased by the free radical-generating compound AAPH","volume":"19","author":"Ohlsson","year":"1995","journal-title":"Free Radic. Biol. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/7\/1577\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:13:22Z","timestamp":1760174002000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/7\/1577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,30]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["molecules25071577"],"URL":"https:\/\/doi.org\/10.3390\/molecules25071577","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,30]]}}}