Smirnov V S, Garshinina A V, Shtro A A, Anikin V B, Galochkina A V, Beliavskaia S V, Zarubaev V V
Vopr Virusol. 2014;59(5):31-8.
Influenza virus is a leading causing factor of infectious respiratory human pathology. The search and development of novel anti-influenza drugs with a wide spectrum of activity is an important goal for medical science. In addition to specific anti-viral activity of the compound, its way of application is of great importance. In this work, we present the results of the study of the activity of a combination of glutamyl-tryptophan with glycirrhyzic acid (GTGA) against oseltamivir-resistant strain of the virus A/Vladivostok/2/09 (H1N1) at per os application on the model of the lethal influenza infection in white mice. The application of the GTGA was shown to decrease the specific mortality of animals (index of protection 43-50%), to increase the mean day of death to 2.5-3.9 days, and to reduce the infectious titer of the virus in the lung tissue to 1.5-1.9 Ig EID50/20 mg. The corresponding values for the reference compound oseltamivir were 14-25%, 1.1-1.9 days and 0.7 Ig EID50/20 mg, respectively, depending on the dose of the virus. The use of the GTGA also led to a reliable increase of the titers of interferon in the blood from 44.3 to 66.3 ME/mL. Morphological analysis revealed that GTGA lead to normalization of the structure of the lung tissue restricting the level of the cytodestruction and inflammation. The results obtained in this work allow the combination studied to be suggested as a promising anti-influenza drug that is active against the drug-resistant virus strains and can be applied orally.
流感病毒是人类传染性呼吸道疾病的主要致病因素。研发具有广泛活性的新型抗流感药物是医学领域的重要目标。除了化合物的特定抗病毒活性外，其应用方式也至关重要。在本研究中，我们展示了谷氨酰 - 色氨酸与甘草酸的组合（GTGA）在经口给药时，对甲型/符拉迪沃斯托克/2/09（H1N1）耐奥司他韦病毒株在小白鼠致死性流感感染模型中的活性研究结果。结果表明，应用GTGA可降低动物的特异性死亡率（保护指数为43 - 50%），将平均死亡天数延长至2.5 - 3.9天，并将肺组织中的病毒感染滴度降低至1.5 - 1.9 Ig EID50/20 mg。根据病毒剂量不同，参考化合物奥司他韦的相应值分别为14 - 25%、1.1 - 1.9天和0.7 Ig EID50/20 mg。使用GTGA还能使血液中干扰素滴度从44.3可靠地提高到66.3 ME/mL。形态学分析显示，GTGA可使肺组织结构正常化，限制细胞破坏和炎症水平。本研究所得结果表明，所研究的这种组合有望成为一种对耐药病毒株有活性且可口服的抗流感药物。
