Singh Jitender, Raina Ashvinder, Sangwan Namrata, Chauhan Arushi, Khanduja Krishan L, Avti Pramod K
Department of Biophysics Postgraduate Institute of Medical Education and Research (PGIMER) Chandigarh India.
Postgraduate Institute of Medical Education and Research (PGIMER) Chandigarh India.
Adv Cell Gene Ther. 2021 Oct;4(4):e114. doi: 10.1002/acg2.114. Epub 2021 Oct 10.
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.
新冠病毒病（COVID-19）的全球病死率约为57%。当下急需研究利用宿主微小RNA（miRNA）抑制病毒复制和传播的抗病毒疗法。运用计算技术预测了与人类（宿主）miRNA具有高度同源性的COVID-19基因组的发夹前体miRNA（pre-miRNA）。鉴定出了与18种病毒前体miRNA具有>80%同源性的前21种宿主miRNA。宿主miRNA与病毒前体miRNA杂交之间的吉布斯自由能（ΔG）产生了具有最高碱基对互补性的最佳5种宿主miRNA。由于种子序列中的碱基对最多，miR-4476与病毒前体miRNA的结合最强（ΔG = -21.8千卡/摩尔）。前体miR-651的二级结构最稳定，原因如下：（1）最小自由能（ΔG = -24.4千卡/摩尔）、能量频率和非规范碱基对最少；（2）茎碱基对数量最多且环大小最小。宿主miRNA与病毒mRNA的相互作用可有效抑制病毒传播和复制。此外，miRNA基因网络和基因本体研究表明，前5种宿主miRNA与参与跨膜受体信号传导、细胞迁移、RNA剪接、神经系统形成以及呼吸系统疾病中肿瘤坏死因子介导的信号传导的宿主基因相互作用。本研究确定了宿主miRNA与病毒前体miRNA的强相互作用、结构稳定性，其基因网络分析为宿主miRNA作为抗COVID-19病毒剂提供了有力证据。
