Ligand-coated polymer for biological binding

季节性甲型流感每年在全世界造成约500，000例死亡和约300 - 500万例严重疾病，特别是婴儿、老年人和更多的一般免疫功能低下患者。在寻找一个持久的解决这个问题的主要障碍之一是流感病毒的高突变频率。这限制了疫苗接种的使用，并且疫苗必须每年重新适应流行的流感毒株突变体，具有巨大的经济成本。目前可用的抗流感病毒药物也出现了类似的问题，这些药物对最新的毒株变得不起作用。最近，已经提出了一种替代方法，靶向保守或不可避免的病毒结构，这些结构必须在毒株之间保留以维持正常的病毒复制。在这方面，正在深入研究的一类重要的病毒抑制剂由展示靶向流感病毒的血凝素糖蛋白的唾液酸受体的多价构建体代表。通常，公认的是，该系统的工作机制依赖于在多价构建体上的唾液酸受体与细胞表面上的类似受体之间产生竞争。其理由是，如果病毒配体通过与这些竞争受体结合而饱和，则它们不能用于与细胞表面结合，从而阻止病毒渗透并在其第一步停止复制周期。这个简单的图景指导了各种试图将结构体系和感染性联系起来的实验研究，但仍有许多问题有待理解。在这方面的一个中心问题是多价构建体结构如何影响其配体的呈递，以及这如何转化为病毒感染性的降低。为了回答这个问题，我们的目标是在这个项目中使用最先进的蒙特卡罗模拟与粗粒度的模型，以提供一个微观图片的聚合物抑制病毒。这些模型将提供我们的系统的定量描述，我们的目标是将他们的结果转化为有用的指导方针，设计和合成新的抗病毒架构。

Seasonal influenza A causes approximately 500,000 deaths and around 3-5 million cases of severe illness annually worldwide, in particular infants, elderly and more in general immunocompromised patients. On of the main hurdles in finding a long-lasting solution to this problem is the high mutation frequency of the influenza virus. This limits the use of vaccination, and vaccine must be annually readapted to circulating influenza strain mutants, with large economic costs. A similar problem arises for currently available antiviral drugs against influenza, which are becoming inactive against the latest strains. Recently, an alternative approach has been suggested, targeting conserved or inevitable viral structures which must be preserved between strain to sustain normal viral replication. In this regard, an important class of viral inhibitors under intensive study is represented by multivalent constructs displaying sialic acid receptors targeting the hemagglutinin glycoproteins of the influenza virus. In general, it is accepted that the working mechanism of this system relies in creating a competition between sialic acid receptors on the multivalent construct and similar receptors on the cell surface. The rational is that if the virus ligands are saturated by binding with these competing receptors, they cannot be used for binding to the cell surface, hence preventing viral penetration and stopping the replication cycle at its very first step. This simple picture has guided various experimental studies trying to link construct architecture and infectivity, but much has still to be understood. A central question in this regard is how the multivalent construct architecture affects the presentation of its ligand, and how this translates into a decrease in viral infectivity. To answer this question, we aim in this project to use state-of-the-art Monte Carlo simulations with coarse-grained models to provide a microscopic picture for viral inhibition by polymers. These models will provide a quantitative description of our system and we aim to translate their results into useful guidelines for the design and synthesis of novel anti-viral architectures.