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

新型冠状病毒的大流行使研究界重新集中于对SARS-CoV-2病毒的合作研究，并发现支持COVID-19在人类中表现的机制。对新型冠状病毒的研究以前所未有的速度取得了进展，这在很大程度上是由于SARS-CoV-2基因组和蛋白质组的快速测定。有希望的是，许多计算方法也被部署来增加我们对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点。鉴于来自原始SARS冠状病毒SARS-CoV的刺突蛋白已知与人血管紧张素转换酶2（hACE 2）相互作用，目前的大部分研究工作集中于更好地表征SARS-CoV-2刺突蛋白及其与ACE 2蛋白的假定相互作用;宿主感染所必需的关键蛋白质-蛋白质相互作用。类似的努力正在进行，以了解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的进化保守功能区域，以告知抗病毒治疗的使用。鉴于这种新型冠状病毒独特的感染性特征，迫切需要一种有效的抗病毒开发策略。病毒潜伏期很长，在此期间，一个人同时具有传染性和无症状，导致全球迅速扩散。利用从最初的SARS-CoV爆发中了解到的信息，大约。2003年，和相关的病毒家族，这一建议有助于我们了解的病毒种间蛋白质相互作用网络。我们的跨学科团队将与Zim Corporation（一家拥有软件和肽生物制药经验的加拿大公司）一起使用由 共同申请人比格尔和绿色研究新型冠状病毒并生产新型基于肽的抗病毒药物，其拮抗被认为对病毒-宿主相互作用至关重要的相互作用。此外，这项研究不仅将开发用于COVID 19治疗的潜在抗病毒肽，而且还将为抗病毒肽开发建立创新资源，因为新病毒被引入人类。

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.