Paniri Alireza, Hosseini Mohammad Mahdi, Moballegh-Eslam Mojtaba, Akhavan-Niaki Haleh
Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
Genetics Department, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
Gene Rep. 2021 Mar;22:100979. doi: 10.1016/j.genrep.2020.100979. Epub 2020 Dec 4.
The COVID-19 pandemic emerges a reminder that wide spectrum discrepancy in response to SARS-CoV-2 infection and antiviral drugs among different populations might be due to their different SNPs and/or miRNAs profile. ACE2 is the major component for SARS-CoV-2s' cell entry, and disruption of its 3D structure could influence virus-ACE2 interaction. In this study we aimed to investigate the consequence of 16,860 SNPs within on its expression as well as protein folding, function, and stability by using several beneficial bioinformatics tools. Only 64 SNPs including 60 intronic, and 4 missense showed different frequencies among different populations. Two missense SNPs including rs149039346 and rs147311723 have been predicted to strongly influence the function and stability of ACE2. rs1514283 creates new acceptor splice site. Also, rs4646175 creates new donor and acceptor splice site. PolymiRTS, and miRSNPs have predicted that rs3746444, rs113808830, and rs3751304 showed a MAF > 0.001, and disrupted mRNA target sites or mRNA function. Finally, rs3746444 hsa-miR-499a-3p, rs113808830 hsa-miR-4532, rs3751304 hsa-miR-6763-3p and hsa-miR-26b-5p were strongly hybridized with and might influence its function. Collectively, this study shed some light on fundamental roles of SNPs for its interaction with COVID-19, and consequently susceptibility to virus. Therefore, different responses of patients with COVID-19 to ACE2 blocker drugs might be due to their unique SNPs. We further discussed the impact of SNPs on miRNAs profile as a factor that may modulate drug response or susceptibility to COVID-19.
新型冠状病毒肺炎疫情提醒人们，不同人群对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染和抗病毒药物的广泛差异可能是由于其不同的单核苷酸多态性（SNP）和/或微小RNA（miRNA）谱。血管紧张素转换酶2（ACE2）是SARS-CoV-2进入细胞的主要成分，其三维结构的破坏可能影响病毒与ACE2的相互作用。在本研究中，我们旨在通过使用几种有益的生物信息学工具，研究16860个SNP对其表达以及蛋白质折叠、功能和稳定性的影响。在不同人群中，只有64个SNP（包括60个内含子SNP和4个错义SNP）表现出不同的频率。包括rs149039346和rs147311723在内的两个错义SNP被预测会强烈影响ACE2的功能和稳定性。rs1514283产生了新的受体剪接位点。此外，rs4646175产生了新的供体和受体剪接位点。PolymiRTS和miRSNPs预测，rs3746444、rs113808830和rs3751304的次要等位基因频率（MAF）>0.001，并破坏了mRNA靶位点或mRNA功能。最后，rs3746444与hsa-miR-499a-3p、rs113808830与hsa-miR-4532、rs3751304与hsa-miR-6763-3p和hsa-miR-26b-5p强烈杂交，可能影响其功能。总的来说，本研究揭示了SNP在其与新型冠状病毒肺炎相互作用以及对病毒易感性方面的基本作用。因此，新型冠状病毒肺炎患者对ACE2阻断药物的不同反应可能是由于其独特的SNP。我们进一步讨论了SNP对miRNA谱的影响，这可能是调节药物反应或对新型冠状病毒肺炎易感性的一个因素。
