Repurposing approved drugs as potent antiviral combinations to treat COVID-19 disease

将已批准的药物重新用作有效的抗病毒组合来治疗 COVID-19 疾病

• 批准号: MR/W021641/1
• 负责人: Ultan Power
• 金额: $ 204.23万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW021641%2F1
• 关键词: Repurposing; approved; drugs; potent; antiviral

SARS-CoV-2 is responsible for the worldwide pandemic that has devasted most countries since it emerged in December 2019. Huge efforts have been made to generate vaccines and drugs to prevent and treat infection, respectively. Vaccine development has proceeded at an unprecendent pace and emergency authorisation was given for a number of vaccines in late 2020 and early 2021. Some drugs have also been shown to have therapeutic benefits against severe COVID-19 disease, most of which are immunemodulators. However, there has been very little success with antiviral therapeutics, with the notable exceptions of remdesivir and monoclonal antibody cocktails. This project, therefore, will seek to bridge this gap and seeks to identify novel drug combinations with enhanced antiviral activities against SARS-CoV-2, the causative agent of COVID-19 disease. We have assembled a very strong team of expertis from Queen's University Belfast, University of Liverpool and University of Oxford. We will initially screen a bespoke library of 140 drugs with known antiviral activity against SARS-CoV-2 for combinations that enhance their antiviral potential. The best combinations will then undergo a robust series of in vitro and in vivo protocols to validate their potential. The data will provide the rationale to make strong recommendations to UK-CTAP for progression to clinical trials. In parallel, we will evaluate the propensity of the drug combinations to elicit drug-resistant mutants, which is an important consideration for drugs that will be used on a massive scale globally. Finally, and in parallel, we have identified 2 large drug libraries that have not been subjected yet to combination drug screening. We will exploit our robust drug screening platform of protocols to identify back-up drug combination candidates to ensure a pipeline of antiviral drugs against SARS-CoV-2 for the future.

SARS-COV-2负责自2019年12月出现以来大多数国家的全球大流行。已做出了巨大的努力，分别为预防和治疗感染而产生疫苗和药物。疫苗的开发已经以非前瞻性的速度进行，并在2020年末和2021年初为多种疫苗提供了紧急授权。一些药物还显示出针对严重的Covid-199疾病具有治疗益处，其中大多数是免疫调节剂。但是，抗病毒治疗剂几乎没有成功，除了Remdesivir和Monoclonal抗体鸡尾酒的显着例外。因此，该项目将寻求弥合这一差距，并试图通过针对SARS-COV-2的抗病毒活性来鉴定新的药物组合，SARS-COV-2是Covid-19疾病的病因。我们组建了一个非常强大的专家团队，来自贝尔法斯特皇后大学，利物浦大学和牛津大学。我们最初将筛选一个定制的文库，该文库具有140种具有针对SARS-COV-2的抗病毒活性的药物，以增强其抗病毒潜力的组合。然后，最佳组合将经历一系列强大的体外和体内方案，以验证其潜力。数据将提供理由，向英国CTAP提出强有力的建议，以进步临床试验。同时，我们将评估药物组合引起耐药突变体的倾向，这是全球大规模使用的药物的重要考虑因素。最后，同时，我们已经确定了尚未进行结合药物筛查的2个大型药物库。我们将利用强大的药物筛查协议平台来识别备用药物组合候选者，以确保未来针对SARS-COV-2的抗病毒药物管道。