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Elucidating the Interactions Between Heparin/Heparan Sulfate and SARS-CoV-2-Related Proteins—An Important Strategy for Developing Novel Therapeutics for the COVID-19 Pandemic
Frontiers in Molecular Biosciences ( IF 3.9 ) Pub Date : 2020-12-16 , DOI: 10.3389/fmolb.2020.628551
Mingjia Yu 1 , Tianji Zhang 2 , Wei Zhang 2 , Qianyun Sun 3 , Hongmei Li 2 , Jin-Ping Li 1, 4
Affiliation  

Owing to the high mortality and the spread rate, the infectious disease caused by SARS-CoV-2 has become a major threat to public health and social economy, leading to over 70 million infections and 1. 6 million deaths to date. Since there are currently no effective therapeutic or widely available vaccines, it is of urgent need to look for new strategies for the treatment of SARS-CoV-2 infection diseases. Binding of a viral protein onto cell surface heparan sulfate (HS) is generally the first step in a cascade of interaction that is required for viral entry and the initiation of infection. Meanwhile, interactions of selectins and cytokines (e.g., IL-6 and TNF-α) with HS expressed on endothelial cells are crucial in controlling the recruitment of immune cells during inflammation. Thus, structurally defined heparin/HS and their mimetics might serve as potential drugs by competing with cell surface HS for the prevention of viral adhesion and modulation of inflammatory reaction. In this review, we will elaborate coronavirus invasion mechanisms and summarize the latest advances in HS–protein interactions, especially proteins relevant to the process of coronavirus infection and subsequent inflammation. Experimental and computational techniques involved will be emphasized.



中文翻译:

阐明肝素/硫酸乙酰肝素与 SARS-CoV-2 相关蛋白之间的相互作用——开发针对 COVID-19 大流行的新型疗法的重要策略

由于死亡率高、传播速度快,SARS-CoV-2引起的传染病已成为公共卫生和社会经济的重大威胁,迄今已导致超过7000万人感染、160万人死亡。由于目前尚无有效的治疗方法或广泛使用的疫苗,因此迫切需要寻找治疗 SARS-CoV-2 感染性疾病的新策略。病毒蛋白与细胞表面硫酸乙酰肝素 (HS) 的结合通常是病毒进入和启动感染所需的一系列相互作用的第一步。同时,选择素和细胞因子(例如IL-6和TNF-α)与内皮细胞表达的HS的相互作用对于控制炎症期间免疫细胞的募集至关重要。因此,结构明确的肝素/HS及其模拟物可能作为潜在的药物,通过与细胞表面HS竞争来预防病毒粘附和调节炎症反应。在这篇综述中,我们将详细阐述冠状病毒的侵袭机制,并总结HS与蛋白质相互作用的最新进展,特别是与冠状病毒感染和随后炎症过程相关的蛋白质。将强调所涉及的实验和计算技术。

更新日期:2021-01-25
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