Creation of a rapid in-silico predictive screening model targeting Coronavirus SARS-CoV-2 to treat COVID-19

创建针对冠状病毒 SARS-CoV-2 的快速计算机预测筛查模型以治疗 COVID-19

• 批准号: 58909
• 金额: $ 9.54万
• 依托单位: PHARMIDEX PHARMACEUTICAL SERVICES LIMITED
• 依托单位国家: 英国
• 项目类别: Feasibility Studies
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=58909
• 关键词: Creation; rapid; silico; predictive; screening

At the time of initial application 15/April/2020, globally COVID-19 had infected over 1,914,916 people and killed over 123,010. Today, 22/October/2020, COVID-19 has infected over 41,104,946 and killed over 1,128,325. COVID-19 could wipe $4trillion from global economy and shrink UK economy triggering a 'big recession'. Epidemiologist prediction that a one-time lockdown will not be sufficient to bring the pandemic under control and that secondary peaks in autumn could be larger than the current one appear to be true and even now are suggesting strong possibility of a 3rd peak in winter. Fears by some authoritative medics and virologist that the "asymptomatic transmission is occurring", someone who has no symptoms from infection with virus, can still infect others, has proved to be the case. Although we have a much better understanding of the virus's behaviour and transmission rate. There is still no clear antiviral drug treatment strategy with proven efficacy nor are there vaccines for its prevention. As suggested in original application vaccines are taking much longer to develop and manufactured at doses to be of immediate benefit. The most likely way out of the pandemic is identification of a combination of small anti-(viral, infective, hypertensive), etc drugs that slows the virus to allow time for immune system to control it before it triggers pneumonia and cytokine storm. Every lost day in not having a treatment has a huge impact on lives lost, families involved, lost productivity as well as create a heavy economic burden. This project aims to help fast-forward the identification of drug treatments for COVID-19. Pharmidex already has comprehensive capabilities and facilities. Initial funding has enabled Pharmidex to recruit an in-silico postdoc expert to work towards establishing a rapid translational drug screening platform to identify and reposition potential combination therapies to treat COVID-19. The key objective of this proposal was to rapidly introduce in-silico prediction capability to the Pharmidex team which has been achieved timely. The project is innovative since only recently the 3D Map of SARS-CoV-2's Spike Protein part of virus that attaches to and infects human cells has been identified. The main area of focus as part of the “Extension for Impact” application will be to incorporate into our newly established in-silico model the recently identified/reported protein structures/targets of SARS-CoV-2. Utilise these new in-silico models in tandem with a database of known drugs to identify/select more efficacious putative drug candidates', using a drug repositioning approach.

截至 2020 年 4 月 15 日首次应用时，全球 COVID-19 已感染超过 1,914,916 人，并导致超过 123,010 人死亡。今天，即 2020 年 10 月 22 日，COVID-19 已感染超过 41,104,946 人，并导致超过 1,128,325 人死亡。 COVID-19 可能会使全球经济损失 4 万亿美元，并使英国经济萎缩，引发“大衰退”。流行病学家预测，一次性封锁不足以控制疫情，秋季的第二次高峰可能会比当前的高峰更大，这一预测似乎是正确的，甚至现在也表明冬季出现第三次高峰的可能性很大。一些权威医学家和病毒学家担心“无症状传播正在发生”，即感染病毒后没有任何症状的人仍然可以感染他人，事实证明确实如此。尽管我们对病毒的行为和传播率有了更好的了解。目前还没有明确且有效的抗病毒药物治疗策略，也没有疫苗可以预防。正如最初应用中所建议的，疫苗的开发和生产需要更长的时间才能产生立竿见影的效果。摆脱大流行的最可能的方法是确定小型抗（病毒、感染、高血压）等药物的组合，这些药物可以减缓病毒的传播速度，以便免疫系统有时间在病毒引发肺炎和细胞因子风暴之前对其进行控制。因得不到治疗而损失的每一天都会对生命损失、家庭损失、生产力损失产生巨大影响，并造成沉重的经济负担。该项目旨在帮助快速确定针对 COVID-19 的药物治疗方法。 Pharmidex 已经拥有全面的能力和设施。初始资金使 Pharmidex 能够招募一名计算机博士后专家，致力于建立一个快速转化药物筛选平台，以识别和重新定位治疗 COVID-19 的潜在联合疗法。该提案的主要目标是向 Pharmidex 团队快速引入计算机预测能力，这一目标已及时实现。该项目具有创新性，因为最近才确定了附着并感染人类细胞的病毒 SARS-CoV-2 刺突蛋白部分的 3D 图。作为“Extension for Impact”应用程序的一部分，主要关注领域是将最近识别/报告的 SARS-CoV-2 蛋白质结构/靶标纳入我们新建立的计算机模型中。利用这些新的计算机模型与已知药物的数据库相结合，使用药物重新定位方法来识别/选择更有效的假定候选药物。