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

截至2020年4月15日首次申请时，全球COVID-19感染人数超过1,914,916人，死亡人数超过123,010人。今天，2020年10月22日，COVID-19已感染超过41,104,946人，死亡人数超过1,128325人。COVID-19可能会从全球经济中抹去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大流行，秋季的第二次高峰可能比目前的高峰更大，这似乎是正确的，即使现在也表明冬季很有可能出现第三次高峰。事实证明，一些权威医学和病毒学家担心“无症状传播”正在发生，即感染病毒后没有症状的人仍然可以感染他人。尽管我们对病毒的行为和传播速度有了更好的了解。目前还没有明确的抗病毒药物治疗策略，证实其有效性，也没有预防这种疾病的疫苗。正如在最初应用中所建议的那样，疫苗的开发和生产所需的剂量要长得多，才能立即产生效益。最有可能摆脱大流行的方法是确定一种小型抗（病毒、感染性、高血压）药物的组合，这些药物可以减缓病毒的传播，让免疫系统有时间在病毒引发肺炎和细胞因子风暴之前控制它。由于得不到治疗而损失的每一天都会对生命损失、相关家庭、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，以确定和重新定位治疗COVID-19的潜在联合疗法。该提案的主要目标是迅速将计算机预测能力引入Pharmidex团队，这已经及时实现。该项目具有创新性，因为直到最近才确定了附着并感染人体细胞的SARS-CoV-2病毒刺突蛋白部分的3D地图。作为“影响扩展”申请的一部分，主要关注领域将是将最近发现/报告的SARS-CoV-2的蛋白质结构/靶标纳入我们新建立的计算机模型。使用药物重新定位方法，将这些新的计算机模型与已知药物数据库结合使用，以确定/选择更有效的假定候选药物。

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.