Deryabin P G, Garaev T M, Finogenova M P, Odnovorov A I
National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Moscow, 123098, Russia.
Russian Peoples' Friendship University of Russia, Moscow, 117198, Russia.
Vopr Virusol. 2019;64(6):268-273. doi: 10.36233/0507-4088-2019-64-6-268-273.
The emergence of influenza virus strains with drug resistance to antiviral drugs requires finding new compounds, potential direct-acting inhibitors. Аdamantane compounds drugs used since the 1960s have lost their activity the resulting due to resistance. Only neuraminidase inhibitors such as zanamivir and oseltamivir have been approved by WHO for influenza treatment. The Russian pharmaceutical drug Arbidol (Umifenovirum) is actively used in Russia. This drug is used to treat influenza in Russia, China and most post-Soviet republics. This work presents a new derivative of aminoadamantane - dichlorohydrate L-histidyl-1-adamantayl ethylamine (2HCl*H-His-Rim), which showed a high level of inhibition of strains of influenza virus A in vitro.
Comparison of antiviral properties of the new synthetic low-molecular inhibitor of influenza A virus replication and Arbidol drug pharmacy.
The compound 2HCl*H-His-Rim was obtained by classical peptide synthesis methods. It was identified by methods of mass spectrometry, infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Its antiviral properties have been studied in vitro for monolayer of cells Vero-E6 infected with a high-virulent strain of A/duck/Novosibirsk/56/06 (H5N1) influenza virus at various injection schemes of the investigated compounds.
The antiviral activity of the 2HCl*H-His-Rim compound against the highly pathogenic strain of the influenza A/H5N1 virus was slightly higher than for the known pharmacy drug arbidol.
The difference in antiviral activity of these two compounds is explained by different mechanisms of action on the viral particle.
The 2HClH-His-Rim compound can be recommended as a candidate for preclinical and clinical trials in order to obtain an etiotropic antiviral drug based on it, due to its high efficacy and economic and synthetic availability. The synthetic compound 2HClH-His-Rim acts on influenza A virus variants resistant to Rimantadine and Amantadine.
对抗病毒药物产生耐药性的流感病毒株的出现,需要寻找新的化合物,即潜在的直接作用抑制剂。自20世纪60年代以来使用的金刚烷类化合物药物由于耐药性而失去了活性。世界卫生组织仅批准了扎那米韦和奥司他韦等神经氨酸酶抑制剂用于流感治疗。俄罗斯药物阿比多尔(乌米芬诺韦)在俄罗斯被广泛使用。该药物在俄罗斯、中国和大多数后苏联共和国用于治疗流感。这项工作展示了一种新型氨基金刚烷衍生物——L-组氨酰-1-金刚烷基乙胺二盐酸盐(2HCl*H-His-Rim),其在体外对甲型流感病毒株表现出高度抑制作用。
比较新型合成的甲型流感病毒复制低分子抑制剂与阿比多尔药物的抗病毒特性。
通过经典肽合成方法获得化合物2HCl*H-His-Rim。通过质谱、红外光谱(IR)和核磁共振光谱(NMR)方法对其进行鉴定。在不同的研究化合物注射方案下,对感染高毒力A/鸭/新西伯利亚/56/06(H5N1)流感病毒的Vero-E6细胞单层进行体外研究,以考察其抗病毒特性。
2HCl*H-His-Rim化合物对甲型H5N1流感病毒高致病性毒株的抗病毒活性略高于已知的阿比多尔药物。
这两种化合物抗病毒活性的差异是由它们对病毒颗粒的不同作用机制所解释的。
鉴于其高疗效以及经济和合成可得性,2HClH-His-Rim化合物可被推荐作为临床前和临床试验的候选药物,以便在此基础上获得一种病因特异性抗病毒药物。合成化合物2HClH-His-Rim对金刚乙胺和金刚烷胺耐药的甲型流感病毒变异株有作用。