开发基于可控化学免疫技术（Altermune）的抗流感病毒疗法

项目名称： 开发基于可控化学免疫技术（Altermune）的抗流感病毒疗法

项目编号： No.21472090

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 宁兴海

作者单位： 南京大学

项目金额： 80万元

中文摘要： 目前，防治流感病毒的主要方式是药物和免疫疫苗疗法。由于流感病毒变异性强，不但快速产生对抗病毒药物的耐药性，而且通过改变病毒表面免疫抗原来逃脱免疫细胞的识别与杀伤。因此急需开发针对快速变异流感病毒的广谱抗病毒药物。本研究项目将结合可控化学免疫技术（Altermune）和纳米医学技术开发集检测和治疗为一体的新型抗流感药物，磁性纳米Altermune链接超分子。该药物通过靶向病毒表面神经氨酸酶的高度保守催化活性位点，可以无视病毒的变异，治疗所有的流感病毒引起的感染。它不仅可以通过抑制病毒表面的神经氨酸酶来抑制病毒的繁殖，而且可以通过引发针对流感病毒的免疫排斥反应清除流感病毒和感染细胞。另外它可以作为MRI造影剂，检测病毒感染状况和治疗效果。因此，该研究不仅有很高的临床应用价值，促进流感治疗，还将对相关的材料、化学、生物医学领域产生推动作用，开发治疗其他疾病如细菌和癌症的新方法。

中文关键词： 流感病毒；药物免疫治疗；Altermune免疫疗法；纳米医学；合理药物设计

英文摘要： Influenza is a serious respiratory infectious disease caused by RNA viruses of the family Orthomyxoviridae, influenza viruses, and causes significant morbidity and mortality every year in the world. In comparison of other respiratory infections caused by viruses such as entero viruses and respiratory syncytial viruses, influenza can cause complications that lead to hospitalization and mortality, particularly in young children and elderly people. Presently, two main classes of antiviral treatments used against influenza are anti-influenza drugs and influenza vaccine. However, their efficacies against influenza viruses are restricted due to short generation times and high mutation rates of viruses. Therefore, there is a great need of developing new, potent antiviral drug against fast mutant influenza viruses such as highly pathogenic influenza H1N1, H5N1 and H7N9 mutants. To solve this issue, we propose a novel anti-influenza therapy based on the Altermune method, which selectively stimulates the body's immune system to act against pathogens or diseases. This research project will combine the Altermune method and nanomedicine technologies to develop a series of multifunctional magnetic nanoparicle based Altermune linkers, which are combination of diagnostics and therapy, theranostics. The magnetic Altermune linkers target the highly conserved bind sites of neuraminidase (NA) proteins on the surface of influenza viruses, therefore they can be used to treat all kinds of mutant viruses. In addition, magnetic Altermune linkers can kill influenza viruses efficiently by inhibiting NA receptors of viruses and redirecting the immune responses to viruses. Furthermore, magnetic Altermune linkers are good NMR contrast agents, and can be used to diagnose virus infections and monitor the therapeutic effects of Altermune linkers. The new magnetic Altermune linkers therefore have the potential to have a significant impact on treating fast mutant influenza viruses and developing the new medical treatments for other diseases including microbial infections, metabolic disorders, cancer and any medical problems where current therapeutic methods are losing out to resistant strains.

英文关键词： Influenza virus;Antivirus drug and immunotherapy;Altermune therapy;Nanomedicine;Drug Design