Developing broad-spectrum antivirals as a rapid response option for future global epidemics

开发广谱抗病毒药物作为未来全球流行病的快速应对选择

• 批准号: EP/W024497/2
• 负责人: Samuel Thomas Jones
• 金额: $ 77.87万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FW024497%2F2
• 关键词: Developing; broad; spectrum; antivirals; rapid

Every year the world health organisation (WHO) assembles a list of priority diseases that require urgent research and development. Each year this list is almost exclusively populated with some of the worlds deadliest viral infections, with each posing a significant public health risk due to their epidemic potential and their total (or insufficient) lack of counter measures. The list includes viruses such as Ebola, Crimean Congo Fever, Lassa Virus and Zika virus. Developing countermeasures against these viruses is extremely challenging and often tackled only one virus at a time. Developing virus specific counter measures is ultimately a short lived strategy as viruses rapidly mutate leading to resistant viral strains or ineffective vaccines. As has become abundantly clear in recent months, our rapid global response to viral outbreaks is virtually non-existent resulting in unnecessary loss of life. When new viral infections are identified it takes too long to develop vaccines, virus specific antiviral drugs and detection systems and when they are eventually developed they are unable to be used for future outbreaks. This delay in development allows the infection to spread globally with potential for large numbers of deaths (even with relatively mild infections) and huge impact on the global economy. If broad-spectrum antiviral drugs existed, equivalent to broad-spectrum antibiotics, viral infections could be contained quickly and/or their spread delayed to give researchers, policy makers and governments the much needed time to deploy other counter measures. Sadly however, no such broad-spectrum antivirals exist and our only current option is to deploy social measures such as closing boarders and self-isolation, which all have significant impacts on the economy. Building on our experience in developing broad-spectrum antiviral nano- and sugar-based materials, we propose to use polymers to create broad-spectrum virucides (Polycides). These polycides would hold some significant advantages over both current and proposed methods of dealing with viral outbreaks. These broad-spectrum polycides would be stable for long periods of time so easily stored, easily deployed and cost effective to produce. These materials could be deployed around the globe, before a viral outbreak occurs, ready for use at the first signs of newly emerging viral outbreaks. Drastically altering our response to outbreaks from reactive to proactive. We have produced generation 1 polymers to test our hypothesis which we have shown is not only possible but that our unoptimised materials are >5000 times more effective than any of our previous (optimised) broad-spectrum antivirals. They are also quicker to produce at larger scales (grams in hours rather than milli-grams in weeks) and use cheaper starting materials. It is of paramount importance that we explore further these extremely exciting results and look to develop a greater understanding and how these materials work. Here we will design, synthesise and then conduct antiviral testing on a range of homo- and block co-polymers, using our preliminary results as a starting point. Through an iterative approach, we aim to identify not only the most potent broad-spectrum antivirals but to investigate their mechanism so as to determine their mode of action and inform the design of future iterations. By partnering with Public Health England these antivirals will be tested against several of the viruses on the WHOs priority diseases list, including Ebola, and surrogate viruses for Lassa fever, Crimean Congo Hemorrhagic fever and Nipah Virus. By the end of this study non-toxic virucidal polymers will have been identified and for the first time a material with broad-spectrum efficacy against some of the worlds most deadly viruses will have been identified. This will lead the way for further studies and funding to develop these antivirals into a much needed antiviral treatment of the future

每年，世界卫生组织（WHO）都会列出一份需要紧急研究和开发的优先疾病清单。每年，这份名单上几乎都有一些世界上最致命的病毒感染，由于其流行潜力和完全（或不充分）缺乏应对措施，每种病毒都构成了重大的公共卫生风险。该名单包括埃博拉病毒、克里米亚刚果热、拉沙病毒和寨卡病毒等病毒。开发针对这些病毒的对策极具挑战性，并且通常一次只能处理一种病毒。开发病毒特异性应对措施最终是一种短暂的策略，因为病毒会迅速突变，导致产生耐药病毒株或无效疫苗。正如最近几个月已经非常清楚的那样，我们对病毒爆发的快速全球反应实际上是不存在的，导致了不必要的生命损失。当发现新的病毒感染时，开发疫苗、病毒特异性抗病毒药物和检测系统需要太长时间，当它们最终开发出来时，它们无法用于未来的爆发。这种发展的延迟使感染在全球范围内蔓延，可能造成大量死亡（即使是相对轻微的感染），并对全球经济产生巨大影响。如果广谱抗病毒药物存在，相当于广谱抗生素，病毒感染可以迅速得到控制和/或延迟其传播，使研究人员，政策制定者和政府有急需的时间部署其他应对措施。然而，可悲的是，没有这样的广谱抗病毒药物存在，我们目前唯一的选择是部署社会措施，如关闭寄宿生和自我隔离，这些都对经济产生重大影响。基于我们在开发广谱抗病毒纳米和糖基材料方面的经验，我们建议使用聚合物来创建广谱杀病毒剂（Polycides）。这些杀虫剂将拥有一些显着的优势，目前和拟议的方法处理病毒爆发。这些广谱杀虫剂将长时间稳定，因此易于储存，易于部署并且生产成本有效。这些材料可以在病毒爆发之前部署在地球仪各地，准备在新出现的病毒爆发的最初迹象时使用。将我们对疫情的反应从被动转为主动。我们已经生产了第1代聚合物来测试我们的假设，我们已经证明这不仅是可能的，而且我们未优化的材料比我们以前的任何（优化的）广谱抗病毒药物都有效5000倍以上。它们也可以更快地以更大的规模生产（以小时计，而不是以数周计），并使用更便宜的起始材料。至关重要的是，我们进一步探索这些极其令人兴奋的结果，并希望进一步了解这些材料的工作原理。在这里，我们将设计，合成，然后进行抗病毒测试的一系列均聚物和嵌段共聚物，使用我们的初步结果作为起点。通过迭代方法，我们的目标不仅是确定最有效的广谱抗病毒药物，而且要研究它们的机制，以确定它们的作用模式，并为未来迭代的设计提供信息。通过与英国公共卫生部合作，这些抗病毒药物将针对世卫组织优先疾病清单上的几种病毒进行测试，包括埃博拉病毒，以及拉沙热、克里米亚刚果出血热和尼帕病毒的替代病毒。到本研究结束时，将确定无毒的杀病毒聚合物，并首次确定对世界上一些最致命病毒具有广谱功效的材料。这将为进一步的研究和资金开发这些抗病毒药物成为未来急需的抗病毒治疗开辟道路