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是自2019年12月出现以来摧毁大多数国家的全球大流行病的罪魁祸首。已经作出巨大努力，分别生产预防和治疗感染的疫苗和药物。疫苗开发以前所未有的速度进行，并于二零二零年底及二零二一年初紧急批准多项疫苗。一些药物也被证明对严重的COVID-19疾病具有治疗益处，其中大多数是免疫调节剂。然而，抗病毒治疗的成功率很低，除了Remdesivir和单克隆抗体鸡尾酒。因此，该项目将寻求弥合这一差距，并寻求确定对COVID-19疾病的病原体SARS-CoV-2具有增强抗病毒活性的新型药物组合。我们汇集了来自贝尔法斯特女王大学、利物浦大学和牛津大学的专家。我们将首先筛选一个包含140种已知抗SARS-CoV-2抗病毒活性的药物的定制库，以增强其抗病毒潜力。然后，最佳组合将经历一系列强有力的体外和体内方案，以验证其潜力。这些数据将为向UK-CTAP提出进入临床试验的强烈建议提供依据。同时，我们将评估药物组合引发耐药突变体的倾向，这是将在全球大规模使用的药物的重要考虑因素。最后，同时，我们已经鉴定了2个尚未进行组合药物筛选的大型药物文库。我们将利用我们强大的药物筛选平台协议，以确定后备药物组合候选人，以确保未来针对SARS-CoV-2的抗病毒药物的管道。