Exploiting the SARS-CoV-2 nsp14 3'-5'-exoribonuclease as a target for antiviral chemotherapy

利用 SARS-CoV-2 nsp14 3-5-核糖核酸外切酶作为抗病毒化疗的靶点

• 批准号: MR/V036904/1
• 负责人: Mark Harris
• 金额: $ 29.03万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=MR%2FV036904%2F1
• 关键词: Exploiting; SARS; CoV; nsp14; exoribonuclease

Many viruses can mutate, or change, their genetic material rapidly. This means that they can avoid our immune system or become resistant to antiviral drugs. This is not the case for coronaviruses as they possess a protein that corrects the errors made by the virus during the production of new viral genetic material. This also means that they are resistant to some antiviral drugs that work by increasing the rate of mutation, inducing fatal errors. This project will use a computer-based approach to identify drugs that can inhibit this error-correcting protein. The structure of the error-correcting protein is known and we will use sophisticated computer algorithms to screen large collections of drugs to identify those that are able to bind to the protein and block its function. Such drugs could be used in combination with mutation-inducing drugs to effectively prevent the virus from growing and thus have clinical benefit for patients suffering from COVID-19 disease, caused by the SARS-CoV-2 coronavirus

许多病毒可以迅速突变或改变其遗传物质。这意味着它们可以避免我们的免疫系统或对抗病毒药物有抵抗力。冠状病毒的蛋白质并非如此，因为它们具有纠正新病毒遗传物质期间病毒误差的蛋白质。这也意味着它们对某些通过增加突变速率而诱发致命误差的抗病毒药物具有抵抗力。该项目将使用基于计算机的方法来识别可以抑制这种错误校正蛋白质的药物。已知误差蛋白的结构已知，我们将使用复杂的计算机算法来筛选大量药物，以识别能够结合蛋白质并阻止其功能的药物。这种药物可以与诱导突变的药物结合使用，以有效防止该病毒生长，从而对患有COVID-19的患者具有SARS-COV-2冠状病毒引起的临床益处