Evaluation of anti-human coronavirus agents

抗人类冠状病毒药物的评价

• 批准号: 16590434
• 负责人: HAYASHI Kyoko
• 金额: $ 2.3万
• 依托单位: University of Toyama (2005-2006)Toyama Medical and Pharmaceutical University (2004)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590434/
• 关键词: human coronavirus; glycoproteins; monoclonal antibody; antiviral assay; ヒトコロナウイルス; 糖蛋白質; ウイルス活性; 作用標的

More than three hundreds of substances including synthesized chemicals and natural products from plants and algae have been assayed for their anti-huma coronavirus (HCoV) activities. Some sulfated polysaccharides isolated from algae showed potent antiviral activity. Other classes of substance with low molecular weight also showed higher antiviral action. In order to elucidate their anti-HCoV targets, we have performed different kinds of experiments and obtained the results as shown below.1. Effect on viral adsorption to host cells : At the first step of viral replication, virus binds to the receptor present on host cell membrane. All the substances with potent anti-HCoV activity were found not to interfere with the binding step.2. Effect on viral penetration into host cells : After binding to host cells, virus particles rapidly penetrate into the cells. Anti-HCoV agents including rhamnan sulfate, dextran sulfate, digitoxin, digoxin, and bufalin showed inhibitory effect on the penetration of HCoV in the range of antiviral concentrations.3. Virucidal activity : Direct inactivity of virus infectivity should attribute to the suppression of HCoV replication at the respiratory organs. So far, a derivative of phenoxazines showed potent virucidal activity without cytotoxicity. The elucidation of the mechanism of this action is in progress.4. Effect on the synthesis of HCoV-specific proteins : Virus-specific proteins were detected by immunoblotting using the monoclonal antibodies. A natural rhamnan sulfate isolated from an edible alga suppressed efficiently the viral protein synthesis when added to the medium at the same time as viral infection.

已经检测了超过300种物质，包括合成的化学物质和来自植物和藻类的天然产物，以确定其抗人类冠状病毒（HCoV）的活性。从海藻中分离得到的硫酸多糖具有较强的抗病毒活性。其他种类的低分子量物质也表现出较高的抗病毒作用。为了阐明它们的抗HCoV靶点，我们进行了不同类型的实验，并获得了如下结果.对病毒吸附到宿主细胞的影响：在病毒复制的第一步，病毒与宿主细胞膜上存在的受体结合。所有具有强抗HCoV活性的物质均不干扰结合步骤.对病毒穿透宿主细胞的影响：病毒颗粒与宿主细胞结合后，迅速穿透细胞。抗HCoV药物硫酸鼠李聚糖、硫酸葡聚糖、洋地黄毒苷、地高辛和蟾蜍灵在一定浓度范围内对HCoV的穿透均有抑制作用.杀病毒活性：病毒感染性的直接失活应归因于呼吸器官中HCoV复制的抑制。到目前为止，吩恶嗪衍生物显示出有效的杀病毒活性而没有细胞毒性。这种作用的机理正在阐明之中。对HCoV特异性蛋白合成的影响：使用单克隆抗体通过免疫印迹检测病毒特异性蛋白。从可食用植物中分离的天然硫酸鼠李聚糖在病毒感染的同时加入培养基中，有效地抑制了病毒蛋白质的合成。