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开我们的免疫系统或对抗病毒药物产生耐药性。冠状病毒的情况并非如此，因为它们拥有一种蛋白质，可以纠正病毒在产生新病毒遗传物质过程中所犯的错误。这也意味着它们对一些通过增加突变率而起作用的抗病毒药物具有耐药性，从而导致致命的错误。该项目将使用基于计算机的方法来识别可以抑制这种纠错蛋白的药物。纠错蛋白的结构是已知的，我们将使用复杂的计算机算法来筛选大量的药物，以确定那些能够与蛋白质结合并阻止其功能的药物。这些药物可以与突变诱导药物联合使用，以有效地防止病毒生长，从而对由SARS-CoV-2冠状病毒引起的COVID-19疾病患者具有临床益处