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

新的冠状病毒大流行使研究界共同重新关注对SARS-CoV-2病毒的合作调查，并发现支持COVID19在人类中表现的机制。新型冠状病毒的研究取得了前所未有的进展，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，许多计算方法也被用来增加我们对SARS-CoV-2的理解，包括对蛋白质功能、三维蛋白质结构的预测，以及对现有小抑制分子的可能治疗靶点。鉴于最初的SARS冠状病毒的Spike蛋白已知与人类血管紧张素转换酶2(HACE2)相互作用，目前的大部分研究工作集中在更好地表征SARS-CoV-2 Spike蛋白及其可能与ACE2蛋白的相互作用，这是宿主感染所必需的一种关键的蛋白质-蛋白质相互作用。为了解SARS-CoV-2蛋白质组的功能和进化特征，正在进行类似的努力，包括确定相关病毒之间进化保守的功能区，以便为抗病毒疗法的使用提供信息。鉴于这种新型冠状病毒独特的传染性特征，迫切需要一种有效的抗病毒发展战略。在漫长的病毒潜伏期内，一个人同时具有传染性和无症状，这导致了快速的全球扩散。利用从最初的SARS-CoV疫情中已知的东西，大约。2003年，以及相关的病毒家族，这一建议有助于我们理解病毒物种间蛋白质相互作用网络。与拥有软件和多肽生物制药经验的加拿大公司Zim Corporation一起，我们的跨学科团队将使用由 共同申请者Bigga和Green研究新型冠状病毒，并生产基于多肽的新型抗病毒药物，以对抗被认为对病毒-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潜在的用于治疗COVID19的抗病毒多肽，而且随着新病毒被引入人类群体，还将为抗病毒多肽开发建立一个创新的资源。

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.