Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Cardiac Primary Prevention Research Center, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Allergy Asthma Immunol. 2020 Oct 18;19(5):456-470. doi: 10.18502/ijaai.v19i5.4461.
The new coronavirus, known as "SARS-CoV-2"; is the cause of one of the most prevalent infectious viral diseases that was recently announced pandemic by the world health organization. Ongoing research in the fields of prevention, management, and therapy establishes a functional scaffold for clinics during the time of crisis. To obtain this goal, it is necessary that all pathophysiologic aspects of COVID-19 from infection to predisposing backgrounds of infection be identified, so that all the ambiguities of researchers regarding transmission mechanisms, variable clinical manifestation, and therapeutic response can be solved. Here, we firstly discuss about the homology screening between nCoV-2019 and beta-coronavirus family using phylogenetic analyses. Secondly, we analyzed the viral motifs to show that viral entry into the host cells requires a primary activation step performed by FURIN and FURIN-like-mediated enzymatic cleavage on the structural glycoprotein. The cleavage increases viral performance by 1000 folds. We then present a comprehensive view on host cells and the significance of gene variants affecting activation enzymes, supportive entry, and spread mechanisms in humans including renin-angiotensin-aldosterone system (RAAS) a pathway results in certain phenotypes or exacerbate infection-related phenotypes in different organs, hence causes variable clinical manifestations. This is followed by discussing about the importance of personalized medicine in nCoV-2019 exposure. Moreover, chemical drugs prescribed for individuals affected with COVID-19, as well as genes involved in drug transport and metabolisms are reviewed as a prelude to drug response. Finally, we suggest some therapeutic approaches developed based on new methods and technology such as anti-sense therapy and antibodies.
新型冠状病毒（SARS-CoV-2）是导致最近世界卫生组织宣布的大流行传染病的原因之一。预防、管理和治疗领域的持续研究为危机时期的临床提供了功能支架。为了实现这一目标，有必要确定 COVID-19 从感染到感染易感性背景的所有病理生理方面，以便解决研究人员在传播机制、可变临床表现和治疗反应方面的所有疑问。在这里，我们首先使用系统发育分析讨论 nCoV-2019 与β冠状病毒家族之间的同源性筛选。其次，我们分析了病毒基序，表明病毒进入宿主细胞需要初级激活步骤，该步骤由 FURIN 和 FURIN 样介导的酶切在结构糖蛋白上完成。切割使病毒性能提高 1000 倍。然后，我们全面介绍了宿主细胞以及影响激活酶、支持进入和传播机制的基因变异的重要性，包括肾素-血管紧张素-醛固酮系统（RAAS）途径，该途径导致某些表型或在不同器官中加重与感染相关的表型，从而导致可变的临床表现。接下来讨论了 nCoV-2019 暴露的个性化医学的重要性。此外，还回顾了针对 COVID-19 患者的个体开出的化学药物以及参与药物转运和代谢的基因，作为药物反应的前奏。最后，我们根据新方法和技术（如反义疗法和抗体）提出了一些治疗方法。
