表观遗传学参与冠状病毒病2019 (COVID-19)大流行的发病机制、检测和管理:述评

T. Yahaya, E. Oladele, A. Muhammed, Abdulhakeem Haruna, Usman U. Liman
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摘要

背景:人们正在加紧寻找冠状病毒病19 (COVID-19)的治疗方法,以遏制该疾病在全球的传播和负担。研究表明,表观遗传修饰影响某些COVID-19病例的发病机制,可作为治疗靶点。目的:本文综述了表观遗传学在COVID-19发病机制和治疗中的作用。方法:从PubMed、SpringerLink、Scopus和Google Scholar等知名学术数据库检索2000年1月至2020年11月发表的相关文章。结果:COVID-19病原体(称为严重急性呼吸综合征冠状病毒2 (SARS-CoV-2))和宿主细胞的表观遗传修饰可能影响对该疾病的易感性或抵抗力。值得注意的是,涉及免疫调节基因和分子(如细胞因子和干扰素调节基因)的脱氧核糖核酸(DNA)甲基化和组蛋白修饰异常可能损害免疫功能,增加宿主的易感性和疾病严重程度。SARS-CoV-2受体(称为血管紧张素转换酶2 (ACE2))的低甲基化导致其过度表达,也可以增强SARS-CoV-2的传染性。此外,SARS-CoV-2可以利用其miRNA劫持宿主的MicroRNA (miRNA),损害免疫功能,增加其传染性。幸运的是,表观遗传变化是可逆的;因此,针对受影响病例的表观遗传变化的治疗可能会逆转COVID-19。结论:SARS-CoV-2或宿主表观基因组的修饰促进了COVID-19的发病机制和严重程度。表观遗传变化是可逆的,因此建议医疗保健提供者制定针对受影响个体的因果机制的治疗程序。
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Involvement of Epigenetics in the Pathogenesis, Testing and Management of Coronavirus Disease 2019 (COVID-19) Pandemic: A Narrative Review
Background: There is an intense search for the Coronavirus Disease 19 (COVID-19) cure, to stem the spread and burden of the disease worldwide. Studies revealed that epigenetic modifications impact the pathogenesis of some COVID-19 cases, which can be used as therapeutic targets.  Objectives: This review articulated the role of epigenetics in the pathogenesis and management of COVID-19. Methods: Relevant articles published between January 2000 and November 2020 were retrieved from reputable academic databases, including PubMed, SpringerLink, Scopus, and Google Scholar. Results: Epigenetic modifications in the COVID-19’s pathogen, called the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and host’s cells may influence susceptibility or resistance to the disease. Notably, abnormal Deoxyribonucleic Acid (DNA) methylation and histone modification involving immune regulatory genes and molecules, such as cytokines and interferon-regulated genes may compromise immune function and enhance the host’s susceptibility and disease severity. The hypomethylation of SARS-CoV-2’s receptor, called the Angiotensin-Converting Enzyme 2 (ACE2), causing its overexpression, can also enhance SARS-CoV-2’s infectivity. Moreover, SARS-CoV-2 can hijack the host’s MicroRNA (miRNA) using its miRNA and compromise the immune function, increasing its infectivity. Fortunately, epigenetic changes are reversible; thus, a therapy that targets the epigenetic changes in the affected case may reverse COVID-19.  Conclusion: Modifications in the SARS-CoV-2 or host epigenome promote the pathogenesis and severity of COVID-19. Epigenetic changes are reversible, so healthcare providers are advised to formulate therapeutic procedures that target the causal mechanisms in the affected individual.
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