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

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重点疾病清单。每年，这份名单上几乎都有一些世界上最致命的病毒感染，由于它们的流行潜力和完全(或不足)缺乏应对措施，每一种都构成了重大的公共卫生风险。这份名单包括埃博拉病毒、克里米亚刚果热、拉萨病毒和寨卡病毒等病毒。开发针对这些病毒的对策具有极大的挑战性，而且一次通常只能解决一种病毒。制定针对病毒的应对措施归根结底是一种短暂的战略，因为病毒迅速变异，导致耐药病毒株或无效疫苗。正如最近几个月非常清楚的那样，我们对病毒爆发的全球快速反应几乎是不存在的，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、针对病毒的抗病毒药物和检测系统需要太长时间，当它们最终被开发出来时，它们无法用于未来的疫情。这种发展的延迟使得这种感染在全球蔓延，有可能导致大量死亡(即使是相对轻微的感染)，并对全球经济造成巨大影响。如果存在相当于广谱抗生素的广谱抗病毒药物，病毒感染可能会迅速得到遏制，和/或推迟其传播，以便为研究人员、政策制定者和政府提供急需的时间来部署其他应对措施。然而，可悲的是，没有这种广谱的抗病毒药物存在，我们目前唯一的选择是部署社会措施，如关闭边境和自我隔离，这些措施都对经济有重大影响。基于我们在开发广谱抗病毒纳米材料和糖基材料方面的经验，我们建议使用聚合物来创建广谱病毒杀菌剂(多杀菌剂)。与目前和拟议的应对病毒暴发的方法相比，这些多杀菌剂将具有一些显著的优势。这些广谱多杀菌剂将长期稳定，因此易于储存、易于部署和生产成本效益高。这些材料可以在病毒爆发之前部署在全球各地，准备在新出现的病毒爆发迹象出现时使用。极大地改变了我们对疫情的反应，从被动变为主动。我们生产了第一代聚合物来测试我们的假设，我们已经证明，我们的假设不仅是可能的，而且我们的未优化材料的有效性是我们之前(优化)的任何广谱抗病毒药物的5000倍。它们也更快地进行更大规模的生产(几小时生产一克，而不是几周一毫克)，并使用更便宜的原材料。至关重要的是，我们必须进一步探索这些极其令人振奋的结果，并寻求更好地了解这些材料是如何工作的。在这里，我们将以我们的初步结果为起点，设计、合成一系列同质和嵌段共聚物，然后对其进行抗病毒测试。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，而且研究它们的作用机制，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组织合作，这些抗病毒药物将针对世卫组织优先疾病名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。到这项研究结束时，无毒的杀毒聚合物将被鉴定出来，第一次，一种对世界上一些最致命的病毒具有广谱功效的材料将被鉴定出来。这将引领进一步的研究和资金，将这些抗病毒药物开发成未来亟需的抗病毒治疗。

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