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.

聚糖是普遍存在于细胞表面的碳水化合物结构，并参与许多生物过程，包括细胞信号传导和肿瘤形成。对聚糖的研究具有挑战性，部分原因是生物相关合成聚糖的可用性有限，以及聚糖-蛋白质相互作用分析的技术挑战。聚糖还在病毒感染中发挥关键作用，介导病毒附着和进入。人诺如病毒是引起病毒性胃肠炎和食源性疾病的主要原因，可导致发病、死亡和经济损失。NoV感染在健康个体中是自限性的，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，频繁出现的新的NoV基因型和变异体可在世界范围内引起大规模爆发和流行。关于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之间的紧密遗传相似性导致了现实的假设，即病毒可能跨越物种屏障，引发大流行变异。重要的是，目前没有治疗或预防NoV感染的疗法。NoV附着于特定聚糖以感染宿主的组织和细胞的要求已经很好地建立，但潜在的机制仍有待阐明。GlycoNoVi正在培训9名研究人员，以解决NoV聚糖相互作用的知识差距，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。这些目标的实现将汇集5个学术界和3个行业领导人在糖科学，糖病毒学和NovV领域，并依靠一个多学科和相互关联的方法，这是在研究导向的WP 1 -5和WP 6 -8分别侧重于培训，推广和协调下降。