Division of Virology, Department of Cellular and Molecular Medicine, Wakayama Medical University Graduate School of Medicine, Wakayama 641-8509, Japan.
Int J Mol Med. 2010 Mar;25(3):433-7. doi: 10.3892/ijmm_00000362.
Viral clearance is a primary concern for parenteral protein biopharmaceuticals. Low pH, detergent/solvent wash, or heating, called pasteurization, has been the main process for virus inactivation. Detergent/solvent wash is also used to treat superficial infectious diseases, including herpes simplex virus (HSV) infections. Herein we examined virus inactivation effects of acidic arginine on HSV type 2 (HSV-2) as a function of pH and temperature in an attempt to find solvent conditions that are effective for virus inactivation, yet are compatible with in vivo applications. Aqueous arginine at 0.7 M was highly effective on HSV-2, more so at lower pH and higher temperature. Its effects were stronger than 0.1 M citrate, 0.1 M citrate/0.6 M NaCl or 0.7 M citrate at any pH and temperature. This demonstrates that strong virus inactivation effects of arginine are not simply due to ionic strength or high concentration and arginine possesses a unique property that results in irreversible damage in virus particles. Such strong virus inactivation effects can be used in vivo for certain superficial infectious diseases, such as genital infections.
病毒清除是肠外蛋白生物制药的主要关注点。低 pH 值、去污剂/溶剂清洗或加热(称为巴氏消毒)一直是病毒灭活的主要工艺。去污剂/溶剂清洗也用于治疗表面传染病,包括单纯疱疹病毒(HSV)感染。在此,我们研究了酸性精氨酸在 pH 值和温度条件下对单纯疱疹病毒 2 型(HSV-2)的病毒灭活效果,试图寻找既有效灭活病毒又与体内应用相兼容的溶剂条件。0.7 M 精氨酸在水中对 HSV-2 具有高度的有效性,在较低 pH 值和较高温度下效果更佳。其效果强于任何 pH 值和温度下的 0.1 M 柠檬酸盐、0.1 M 柠檬酸盐/0.6 M NaCl 或 0.7 M 柠檬酸盐。这表明精氨酸的强烈病毒灭活效果并非仅仅归因于离子强度或高浓度,并且精氨酸具有独特的性质,导致病毒颗粒不可逆损伤。这种强烈的病毒灭活效果可在体内用于某些表面传染病,如生殖器感染。