Understanding the Role of Glycans in Human Norovirus Infection: a Key to Unlock New Therapies (GlycoNoVi)

了解聚糖在人类诺如病毒感染中的作用：开启新疗法的关键 (GlycoNoVi)

• 批准号: EP/X024903/1
• 负责人: Rob Field
• 金额: $ 33.8万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX024903%2F1
• 关键词: Understanding; Role; Glycans; Human; Norovirus

Glycans are carbohydrate structures ubiquitously found on the surface of cells and take part in many biological processes, including cell signaling and neoplasia. Research on glycans is challenging in part due to the limited availability ofbiologically relevant synthetic glycans and to technical challenges in the analysis of glycan-protein interactions. Glycans also exhibit key roles in viral infections, mediating virus attachment and entry. Human noroviruses (NoVs) are themajor cause of viral gastroenteritis and foodborne illnesses causing morbidity, mortality and economic losses. NoV infections are self-limiting in healthy individuals but are associated with severe complications in immunocompromisedindividuals, the elderly and young children. In addition, frequently occurring new NoV genotypes and variants can cause large outbreaks and epidemics worldwide. Very little is known about NoV infections in most non-human hosts and theclose genetic similarities between some animal and human NoVs leads to the realistic hypothesis that the virus might jump the species barrier triggering pandemic variants. Importantly, no therapy is currently available to treat or preventNoV infections. The requirement for NoVs to attach to specific glycans to infect hosts' tissues, and cells, has been well established but the underlying mechanisms remain to be elucidated. Going beyond the state-of-the-art, the overallaims of GlycoNoVi is training 9 researchers to address knowledge gaps on NoV glycan interactions and investigate the exciting possibility of developing synthetic glycans as antiviral strategies to treat NoV infection. These aims will beachieved bringing together 5 academic and 3 industrial leaders in glycoscience, glycovirology and NoV field and relying on a multidisciplinary and interconnected approach which is declinate in research-oriented WP1-5 and WP6-8 focusedrespectively on training, outreach and coordination.

聚糖是细胞表面普遍存在的碳水化合物结构，参与许多生物过程，包括细胞信号传导和肿瘤形成。聚糖的研究具有挑战性，部分原因是生物学相关的合成聚糖的可用性有限以及聚糖-蛋白质相互作用分析中的技术挑战。聚糖在病毒感染、介导病毒附着和进入中也发挥着关键作用。人类诺如病毒 (NoV) 是病毒性胃肠炎和食源性疾病的主要原因，可导致发病率、死亡率和经济损失。 NoV 感染在健康个体中具有自限性，但在免疫功能低下的个体、老年人和幼儿中与严重并发症相关。此外，频繁出现的新NoV基因型和变种可能导致全球范围内的大规模暴发和流行。人们对大多数非人类宿主中的 NoV 感染知之甚少，并且一些动物和人类 NoV 之间的密切遗传相似性导致了一种现实的假设，即该病毒可能跨越物种屏障，引发大流行变异。重要的是，目前尚无治疗或预防新型病毒感染的疗法。 NoV 附着于特定聚糖以感染宿主组织和细胞的要求已得到充分确定，但其潜在机制仍有待阐明。 GlycoNoVi 的总体目标是超越最先进水平，培训 9 名研究人员，以解决 NoV 聚糖相互作用的知识空白，并研究开发合成聚糖作为治疗 NoV 感染的抗病毒策略的令人兴奋的可能性。这些目标将汇集糖科学、糖病毒学和 NoV 领域的 5 名学术领导者和 3 名工业领导者，并依靠多学科和相互关联的方法来实现，该方法在以研究为导向的 WP1-5 和 WP6-8 中分别侧重于培训、推广和协调。