利米洛韦

利米洛韦（INN：Riamilovir ），又称三氮唑核苷（Triazavirin），是一种广谱抗病毒药物。由俄罗斯乌拉尔联邦大学、俄罗斯科学院、乌拉尔生物制药中心和麦德森制药（Medsintez）联合开发。该药物中含有三唑三嗪结构，是一种非核苷酸抗病毒药物新结构类型。 利米洛韦的主要通过合成嘌呤核苷酸碱基类似物来抑制病毒RNA基因片段的复制，由此达到抑制病毒繁殖的效果。 利米洛韦最初是作为抗诸如H5N1等流感病毒的药物而研发的，早期已经有许多关于抗流感病毒效果的测试。随后又发现其对如蜱传脑炎病毒（英语：Tick-borne encephalitis virus）等其他病毒亦有效果，同时也针对高危型流感病毒感染、流感后肺部二次细菌感染等疾病以及拉沙熱、埃博拉等致命病毒性疾病的治疗效果进行研究。 利米洛韦目前已经通过了临床测试，并对急性呼吸道病毒感染展现出抗病毒活性。 2020年，俄罗斯，中国和南非三国开展了利米洛韦抗新冠病毒（SARS-CoV-2）活性的研究。利米洛韦的作用机制仍存在争议。迄今尚未有关于利米洛韦对SARS-CoV-2或流感靶蛋白活性的论文发表。 2014年8月，俄罗斯卫生部通过了利米洛韦的注册登记，可凭处方即可购买。同时利米洛韦的注册程序已在南非开展。 一篇论文批评利米洛韦的研发过程没有符合双盲实验和随机化受试对象要求，并且受试者仅有66人，其中有44人为对照组。 中国初步证实俄罗斯药物三氮唑核苷抗击新冠病毒的疗效. 俄罗斯卫星通讯社. 2020年9月11日 [2024-07-09].  Triazaverin Is Officially Recommended. www.medsintez.com. [2021-02-25].  Rusinov VL, Sapozhnikova IM, Ulomskii EN, Medvedeva NR, Egorov VV, Kiselev OI, Deeva EG, Vasin AV, Chupakhin ON. Nucleophilic substitution of nitro group in nitrotriazolotriazines as a model of potential interaction with cysteine-containing proteins.. Chemistry of Heterocyclic Compounds. 2015, 51 (3): 275–280. S2CID 83702396. doi:10.1007/s10593-015-1695-4 .  Karpenko I, Deev S, Kiselev O, Charushin V, Rusinov V, Ulomsky E, Deeva E, Yanvarev D, Ivanov A, Smirnova O, Kochetkov S, Chupakhin O, Kukhanova M. Antiviral properties, metabolism, and pharmacokinetics of a novel azolo-1,2,4-triazine-derived inhibitor of influenza A and B virus replication. Antimicrobial Agents and Chemotherapy. May 2010, 54 (5): 2017–2022. PMC 2863629 . PMID 20194696. doi:10.1128/AAC.01186-09.  Loginova SI, Borisevich SV, Rusinov VL, Ulomskiĭ UN, Charushin VN, Chupakhin ON. [Investigation of Triazavirin antiviral activity against tick-borne encephalitis pathogen in cell culture]. Antibiotiki i Khimioterapiia. 2014, 59 (1–2): 3–5. PMID 25051708 （俄语）.  Loginova SI, Borisevich SV, Maksimov VA, Bondarev VP, Kotovskaia SK, Rusinov VL, Charushin VN. [Investigation of triazavirin antiviral activity against influenza A virus (H5N1) in cell culture]. Antibiotiki i Khimioterapiia. 2007, 52 (11–12): 18–20. PMID 19275052 （俄语）.  Kiselev OI, Deeva EG, Mel'nikova TI, Kozeletskaia KN, Kiselev AS, Rusinov VL, Charushin VN, Chupakhin ON. [A new antiviral drug Triazavirin: results of phase II clinical trial]. Voprosy Virusologii. 2012, 57 (6): 9–12. PMID 23477247 （俄语）.  Kasianenko KV, Lvov NI, Maltsev OV, Zhdanov KV. Nucleoside analogues for the treatment of influenza: History and experience. Journal of Infectology. 9 October 2019, 11 (3): 20–26. S2CID 241604614. doi:10.22625/2072-6732-2019-11-3-20-26  （俄语）.  Sologub TV, Tokin II, Midikari AS, Tsvetkov VV. A comparative efficacy and safety of using antiviral drugs in therapy of patients with influenza. Infekcionnye Bolezni. 2017, 15 (3): 25–32. doi:10.20953/1729-9225-2017-3-25-32 （俄语）.  Loginova SY, Borisevich SV, Rusinov VL, Ulomsky EN, Charushin VN, Chupakhin ON, Sorokin PV. [Investigation of Therapeutic Efficacy of Triazavirin Against Experimental Forest-Spring Encephalitis on Albino Mice]. Antibiotiki i Khimioterapiia. 2015, 60 (7–8): 11–13. PMID 26863736 （俄语）.  Leneva IA, Falynskova IN, Makhmudova NR, Glubokova EA, Kartashova NP, Leonova EI, Mikhailova NA, Shestakova IV. Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice. Microbiology Independent Research Journal. 2018-02-22, 4 (1). doi:10.18527/2500-2236-2017-4-1-52-57 .  Target: Ebola. Pravda. 2014-12-22 [18 January 2015].  Yekaterinburg pharmacies to sell domestic antiviral drug. Yekaterinburg News Reports. 6 January 2015 [18 January 2015]. （原始内容存档于18 January 2015）.  Cox S. Ebola crisis: Vaccine 'too late' for outbreak. BBC News, 17 October 2014. BBC News. 2014-10-17.  Bora K. Russia Will Begin Testing Triazavirin, Used For Lassa Fever, And Other Drugs On Ebola: Health Ministry.. International Business Times. 12 November 2014.  Kezina D. New antiviral drug from Urals will help fight Ebola and other viruses.. Russia Beyond the Headlines. 12 November 2014.  Tikhonova EP, Kuz'mina TY, Andronova NV, Tyushevskaya OA, Elistratova TA, Kuz'min AE. Study of effectiveness of antiviral drugs (umifenovir, triazavirin) against acute respiratory viral infections. Kazan Medical Journal. 2018-04-15, 99 (2): 215–223. ISSN 2587-9359. doi:10.17816/KMJ2018-215  （俄语）.  Verevshchikov VK, Shemyakina EK, Sabitov AU, Khamanova YB. The Possibilities of Etiotropic Therapy for Influenza and ARVI with Taking into Account the Period of Hospitalization and the Risk of Developing Secondary Complications. Antibiotics and Chemotherapy. 2019 [2021-02-25].  Lioznov DA, Tokin II, Zubkova TG, Sorokin PV. [The practice of using a domestic antiviral drug in the etiotropic therapy of acute respiratory viral infection]. Terapevticheskii Arkhiv. December 2020, 92 (12): 160–164. PMID 33720589. doi:10.26442/00403660.2020.12.200427  （俄语）.  Verevshchikov VK, Shemyakina EK, Sabitov AU, Batskalevich NA. Modern Etiotropic Therapy of Influenza and ARVI in Adult Patients with Premorbid Pathology. Antibiotics and Chemotherapy. 2018 [2021-02-25].  Phiri C. China Tests Russian Antiviral Drug Which Might Treat Coronavirus As Moscow Warns Of Possible 'Mass Outbreak'. Zambia Reports. 5 February 2020 [11 February 2020]. （原始内容存档于5 February 2020）.  Wu X, Yu K, Wang Y, Xu W, Ma H, Hou Y, Li Y, Cai B, Zhu L, Zhang M, Hu X, Gao J, Wang Y, Qin H, Wang W, Zhao M, Wu X, Zhang Y, Li L, Li K, Du Z, Mol BW, Yang B. Efficacy and Safety of Triazavirin Therapy for Coronavirus Disease 2019: A Pilot Randomized Controlled Trial. Engineering. October 2020, 6 (10): 1185–1191. PMC 7476906 . PMID 32923016. S2CID 221520816. doi:10.1016/j.eng.2020.08.011 .  Brandt K. SA study to trial antiviral Triazavirin as COVID-19 treatment. ewn.co.za. [2021-02-25] （英语）.  Discussion on Russia's antiviral drug Triazavirin. SABC News. 21 January 2021 –通过YouTube.  Sabitov AU, Belousov VV, Edin AS, Oleinichenko EV, Gladunova EP, Tikhonova EP, Kuzmina TY, Kalinina YS, Sorokin PV. Practical Experience of Using Riamilovir in Treatment of Patients with Moderate COVID-19. Antibiotiki i Khimioterapiya. 21 November 2020, 65 (7–8): 27–30. S2CID 229508119. doi:10.37489/0235-2990-2020-65-7-8-27-30 .  Chupakhin ON, Rusinov VL, Varaksin MV, Ulomskiy EN, Savateev KV, Butorin II, Du W, Sun Z, Charushin VN. Triazavirin-A Novel Effective Antiviral Drug. International Journal of Molecular Sciences. November 2022, 23 (23): 14537. PMC 9738222 . PMID 36498864. doi:10.3390/ijms232314537 .