COVID-19: Annotating and controlling the inter-species protein interactome through the development of peptide inhibitors for SARS-CoV-2 and human protein interactions

COVID-19：通过开发 SARS-CoV-2 和人类蛋白质相互作用的肽抑制剂来注释和控制种间蛋白质相互作用组

• 批准号: 555217-2020
• 负责人: Biggar, Kyle
• 金额: $ 3.64万
• 依托单位: Carleton University
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=705791
• 关键词: COVID; 19; Annotating; controlling; inter

The novel coronavirus pandemic has collectively re-focused the research community towards a collaborative investigation of the SARS-CoV-2 virus and discovery of the mechanisms supporting COVID19 manifestation in humans. Research on the novel coronavirus has progressed with unprecedented speed due, in large part, the rapid determination of the SARS-CoV-2 genome and proteome. Promisingly, many computational approaches have also been deployed to increase our understanding of SARS-CoV-2, including the prediction of protein function, three-dimensional protein structure, and possible therapeutic targets for existing small inhibitory molecules. Given that the Spike protein from the original SARS coronavirus, SARS-CoV, is known to interact with the human Angiotensin-Converting Enzyme 2 (hACE2), much of the current research effort is focused to better characterize the SARS-CoV-2 Spike protein and its putative interaction with the ACE2 protein; a critical protein-protein interaction necessary for host infection. Similar efforts are being made to understand the functional and evolutionary characteristics of the SARS-CoV-2 proteome, including the determination of evolutionary conserved functional regions between related viruses to inform the use of anti-viral therapeutics. Given the unique infectivity characteristics of this novel coronavirus, the need for an effective strategy of anti-viral development is pressing. The long viral incubation period, during which an individual is simultaneously contagious and asymptomatic, has resulted in rapid global proliferation. Leveraging what is known from the original SARS-CoV outbreak, circa. 2003, and related viral families, this proposal contributes to our understanding of the viral inter-species protein interaction network. Together with Zim Corporation, a Canadian company with software and peptide biopharmaceutical experience, our cross-disciplinary team will use algorithms co-developed by co-applicants Biggar and Green to study the novel coronavirus and to produce novel peptide-based anti-viral drugs that antagonize interactions deemed critical to the virus-host interaction. Further, not only will this research develop potential anti-viral peptides for COVID19 treatment, but also establish an innovative resource for anti-viral peptide development as new viruses are introduced to the human population.

新型的冠状病毒大流行集体将研究界重点关注，以对SARS-COV-2病毒进行合作研究，并发现支持人类Covid19表现的机制。关于新型冠状病毒的研究以空前的速度发展，这在很大程度上是SARS-COV-2基因组和蛋白质组的快速测定。有希望的是，还部署了许多计算方法，以提高我们对SARS-COV-2的理解，包括预测蛋白质功能，三维蛋白质结构以及现有小抑制分子的可能治疗靶标。鉴于已知原始SARS冠状病毒SARS-COV的尖峰蛋白与人类血管紧张素转化酶2（HACE2）相互作用，因此当前的许多研究工作都集中在以更好地表征SARS-COV-2 Spike蛋白它与ACE2蛋白的推定相互作用；宿主感染所需的关键蛋白质蛋白质相互作用。采取类似的努力来了解SARS-COV-2蛋白质组的功能和进化特征，包括确定相关病毒之间进化保守的功能区域，以告知抗病毒疗法的使用。考虑到这种新型冠状病毒的独特感染特征，对有效的抗病毒发育策略的需求正在迫切。长期的病毒孵育期，在该期间同时具有传染性和无症状的人，导致了全球快速的增殖。利用最初的SARS-COV爆发中已知的内容。 2003年及相关病毒家族，该提案有助于我们对病毒间种间蛋白质相互作用网络的理解。与Zim Corporation（一家具有软件和肽生物制药经验的加拿大公司）一起，我们的跨学科团队将使用共同开发的算法 Biggar和Green的共同申请者研究了新型冠状病毒，并产生新的基于肽的抗病毒药物，这些药物对拮抗对病毒宿主相互作用至关重要的相互作用。此外，这项研究不仅会为CoVID19治疗开发潜在的抗病毒肽，而且还将为抗病毒肽发育建立创新的资源，因为将新病毒引入了人群。