Kocik Janusz, Kołodziej Marcin, Joniec Justyna, Kwiatek Magdalena, Bartoszcze Michał
Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
Biological Threats Identification and Countermeasure Center of MIHE, Puławy, Poland.
Acta Biochim Pol. 2014;61(3):509-13. Epub 2014 Sep 12.
The aim of this study was to investigate the in vitro cytotoxicity of oseltamivir derivatives and determine their activity against A/H1N1/PR/8/34 and A/H3N2/HongKong/8/68 - strains of influenza virus. Antiviral activity of these compounds was determined by using two methods. MTT staining was used to assess the viability of MDCK cells infected with influenza viruses and treated with various concentrations of drugs. In parallel, the effect of drugs on viral replication was assessed using the hemagglutination test. The most toxic compounds were: OS-64, OS-35, OS-29, OS-27 and OS-25, whereas OS-11, OS-20 and OS-23 were the least toxic ones. Statistically significant antiviral effect at a higher virus dose was shown by compounds: OS-11, OS-20, OS-27, OS-35, and OS-64. H3N2 virus was sensitive to 10-times lower concentrations of OS-11 and OS-35 than H1N1. At a lower infection dose, the antiviral activity was observed for OS-11, OS 27, OS-35 and OS-20. OS-64 turned out to be effective only at a high concentration. OS-23 showed no antiviral effect.
本研究的目的是调查奥司他韦衍生物的体外细胞毒性，并确定其对甲型H1N1/PR/8/34和甲型H3N2/香港/8/68流感病毒株的活性。这些化合物的抗病毒活性通过两种方法测定。MTT染色用于评估感染流感病毒并用不同浓度药物处理的MDCK细胞的活力。同时，使用血凝试验评估药物对病毒复制的影响。毒性最大的化合物是：OS-64、OS-35、OS-29、OS-27和OS-25，而毒性最小的是OS-11、OS-20和OS-23。化合物OS-11、OS-20、OS-27、OS-35和OS-64在较高病毒剂量下显示出统计学上显著的抗病毒作用。H3N2病毒对OS-11和OS-35的敏感性比对H1N1低10倍的浓度。在较低感染剂量下，观察到OS-11、OS 27、OS-35和OS-20具有抗病毒活性。OS-64仅在高浓度下有效。OS-23没有显示出抗病毒作用。
