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MicroRNA 模拟物或抑制剂作为针对 COVID-19 的抗病毒治疗方法。

MicroRNA Mimics or Inhibitors as Antiviral Therapeutic Approaches Against COVID-19.

机构信息

Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.

Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.

出版信息

Drugs. 2021 Apr;81(5):517-531. doi: 10.1007/s40265-021-01474-5. Epub 2021 Feb 27.

Abstract

Coronaviruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) pandemic, present a significant threat to human health by inflicting a wide variety of health complications and even death. While conventional therapeutics often involve administering small molecules to fight viral infections, small non-coding RNA sequences, known as microRNAs (miRNAs/miR-), may present a novel antiviral strategy. We can take advantage of their ability to modulate host-virus interactions through mediating RNA degradation or translational inhibition. Investigations into miRNA and SARS-CoV-2 interactions can reveal novel therapeutic approaches against this virus. The viral genomes of SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) were searched using the Nucleotide Basic Local Alignment Search Tool (BLASTn) for highly similar sequences, to identify potential binding sites for miRNAs hypothesized to play a role in SARS-CoV-2 infection. miRNAs that target angiotensin-converting enzyme 2 (ACE2), the receptor used by SARS-CoV-2 and SARS-CoV for host cell entry, were also predicted. Several relevant miRNAs were identified, and their potential roles in regulating SARS-CoV-2 infections were further assessed. Current treatment options for SARS-CoV-2 are limited and have not generated sufficient evidence on safety and efficacy for treating COVID-19. Therefore, by investigating the interactions between miRNAs and SARS-CoV-2, miRNA-based antiviral therapies, including miRNA mimics and inhibitors, may be developed as an alternative strategy to fight COVID-19.

摘要

冠状病毒,如导致 2019 年冠状病毒病(COVID-19)大流行的严重急性呼吸综合征冠状病毒 2(SARS-CoV-2),通过造成各种健康并发症甚至死亡,对人类健康构成重大威胁。虽然传统疗法通常涉及施用小分子来对抗病毒感染,但小非编码 RNA 序列,称为 microRNAs(miRNAs/miR-),可能代表一种新的抗病毒策略。我们可以利用它们通过介导 RNA 降解或翻译抑制来调节宿主-病毒相互作用的能力。对 miRNA 和 SARS-CoV-2 相互作用的研究可以揭示针对该病毒的新治疗方法。使用核苷酸基本局部比对搜索工具(BLASTn)在 SARS-CoV-2、严重急性呼吸综合征冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)的病毒基因组中搜索高度相似的序列,以鉴定假定在 SARS-CoV-2 感染中发挥作用的 miRNA 的潜在结合位点。还预测了靶向血管紧张素转换酶 2(ACE2)的 miRNA,ACE2 是 SARS-CoV-2 和 SARS-CoV 用于宿主细胞进入的受体。确定了一些相关的 miRNA,并进一步评估了它们在调节 SARS-CoV-2 感染中的潜在作用。目前 SARS-CoV-2 的治疗选择有限,并且在治疗 COVID-19 的安全性和疗效方面没有产生足够的证据。因此,通过研究 miRNA 与 SARS-CoV-2 之间的相互作用,可以开发基于 miRNA 的抗病毒疗法,包括 miRNA 模拟物和抑制剂,作为对抗 COVID-19 的替代策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f70/8052218/9abdecb8093f/40265_2021_1474_Fig1_HTML.jpg

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