新冠病毒基因组抗病毒同源人mirna的鉴定

Jitender Singh, Ashvinder Raina, Namrata Sangwan, Arushi Chauhan, Krishan L. Khanduja, Pramod K. Avti
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引用次数: 2

摘要

COVID-19的全球致死率约为57%。研究利用宿主microRNA (miRNA)抑制病毒复制和传播的可能抗病毒治疗是当务之急。利用计算技术预测新冠病毒基因组发夹前体miRNA (pre-miRNA)与人(宿主)miRNA具有高度同源性。鉴定出与18个病毒前mirna具有80%同源性的前21个宿主mirna。宿主miRNAs与病毒前miRNAs杂交的吉布斯自由能(ΔG)结果显示,5个最佳的宿主miRNAs具有最高的碱基对互补性。由于在种子序列中存在最大碱基配对,miR-4476与病毒pre-miRNA结合最强(ΔG =−21.8 kcal/mol)。Pre-miR-651二级结构最稳定,因为(1)最小自由能(ΔG =−24.4 kcal/mol)、能量频率和非规范碱基配对最小,(2)茎碱基配对最多,环尺寸小。宿主mirna -病毒mrna相互作用可有效抑制病毒的传播和复制。此外,miRNAs基因网络和基因本体研究表明,在呼吸系统疾病中,前5大宿主miRNAs与宿主基因相互作用,参与跨膜受体信号传导、细胞迁移、RNA剪接、神经系统形成和肿瘤坏死因子介导的信号传导。本研究发现宿主miRNA/病毒pre-miRNA相互作用强,结构稳定,其基因网络分析为宿主miRNA作为抗病毒COVID-19药物提供了有力证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Identification of homologous human miRNAs as antivirals towards COVID-19 genome

Identification of homologous human miRNAs as antivirals towards COVID-19 genome

The COVID-19 fatality rate is ~57% worldwide. The investigation of possible antiviral therapy using host microRNA (miRNA) to inhibit viral replication and transmission is the need of the hour. Computational techniques were used to predict the hairpin precursor miRNA (pre-miRNAs) of COVID-19 genome with high homology towards human (host) miRNA. Top 21 host miRNAs with >80% homology towards 18 viral pre miRNAs were identified. The Gibbs free energy (ΔG) between host miRNAs and viral pre-miRNAs hybridization resulted in the best 5 host miRNAs having the highest base-pair complementarity. miR-4476 had the strongest binding with viral pre-miRNA (ΔG = −21.8 kcal/mol) due to maximum base pairing in the seed sequence. Pre-miR-651 secondary structure was most stable due to the (1) least minimum free energy (ΔG = −24.4 kcal/mol), energy frequency, and noncanonical base pairing and (2) maximum number of stem base pairing and small loop size. Host miRNAs–viral mRNAs interaction can effectively inhibit viral transmission and replication. Furthermore, miRNAs gene network and gene-ontology studies indicate top 5 host miRNAs interaction with host genes involved in transmembrane-receptor signaling, cell migration, RNA splicing, nervous system formation, and tumor necrosis factor-mediated signaling in respiratory diseases. This study identifies host miRNA/virus pre-miRNAs strong interaction, structural stability, and their gene-network analysis provides strong evidence of host miRNAs as antiviral COVID-19 agents.

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