Biological Impacts of MicroRNAs in Covid-19: Implications for Anti-Viral miRNA-Based Therapies

authors:

avatar Mohammad Hasan Soheilifar ORCID 1 , 2 , * , avatar Hoda Keshmiri Neghab ORCID 3 , 4 , avatar Parviz Basiri 2

Department of Medical Laser, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
Research Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

How To Cite Soheilifar M H , Keshmiri Neghab H , Basiri P. Biological Impacts of MicroRNAs in Covid-19: Implications for Anti-Viral miRNA-Based Therapies. Arch Clin Infect Dis. 2020;15(5):e104140. https://doi.org/10.5812/archcid.104140.

Dear Editor,

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a novel sever pathogenic coronavirus (CoVs) causing coronavirus disease 2019 (COVID-19), which has become an international concern due to the outbreak and crucial health burden worldwide. SARS-CoV-2 belongs to Coronaviridae family, which are positive single-stranded RNA and contains the largest RNA genome in viruses (1). Interestingly, miRNAs are small non-coding regulator RNAs that involved in various biologic and pathologic processes such as inflammatory responses as well as viral infection. It has been shown that miR-9, miR-98, miR-223, and miR-214 expression in CoVs-infected host cells could be changed and subsequently leads to modification in cytokines production (2). miRNA-target prediction via bioinformatics analysis revealed that miR-5197-3p could interact with SARS-CoV-2 gRNA, which could not target any genes in the human genome (3). Therefore, miRNA-based therapy could be proposed for SARS-CoV-2 treatment through the viral genome suppression. In this line, a comparative viral genome analysis showed that six host miRNAs, including let-7a, miR-101, miR-126, miR-23b, miR-378, and miR-98 might be considered as anti-viral miRNAs which could suppress SARS-CoV-2 target genes including nonstructural protein (nsp), nucleocapsid and spike glycoprotein that (4). Based on our analysis through the VIRmiRNA database, the most of virus-derived miRNAs involved in IFNβ related pathway. COVID-19 treatment with IFNβ, especially in the early stage of the disease, has a beneficial effect in patients (5). PANTHER (protein annotation through evolutionary relationship) analysis indicated that SARS-CoV-2-derived putative miRNAs might inhibit transcription factors and regulators such as STAT1 (6). Suppression of STAT1 expression as a major anti-viral mediator in the IFN signaling pathway by SARS-CoV ORF6 protein suggests that IFN treatment could be more effectiveness in COVID-19 patients (7). Zhi Liu et al., performed computational approaches demonstrated that SARS-CoV-2-derived MR-147-3p via inhibition of transmembrane protease, serine 2 (TMPRSS2) enhances the viral spike (S) priming as the predicted target of miR-4661-3p which facilitates the virus entry into the gastrointestinal tract (8). In addition, gastrointestinal symptoms are associated with poor prognosis in COVID-19 patients. Although these results are preliminary and experimental attempts are inevitable for better pre-clinical and clinical assessment of COVID-19. In summary, it can be concluded that cost and time benefits in silico analysis of virus and/or host miRNAs as well as the target genes network would be a valuable point of view to figure out the underlying molecular mechanisms of COVID-19. Moreover, virus or host genome scanning may lead to discover the promising targets in order to control viral pathogenicity with anti-viral miRNA-based therapies.

References

  • 1.

    Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis. 2020. https://doi.org/10.1016/j.jpha.2020.03.001.

  • 2.

    Leon-Icaza SA, Zeng M, Rosas-Taraco AG. microRNAs in viral acute respiratory infections: immune regulation, biomarkers, therapy, and vaccines. ExRNA. 2019;1(1).

  • 3.

    Ivashchenko AT, Rakhmetullina AK, Aisina DE. How miRNAs can protect humans from coronaviruses COVID-19, SARS-CoV, and MERS-CoV. ResearchSquare. 2020.

  • 4.

    Sardar R, Satish D, Birla S, Gupta D. Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis. Biorxiv. 2020. https://doi.org/10.1101/2020.03.21.001586.

  • 5.

    Sallard E, Lescure F, Yazdanpanah Y, Mentre F, Peiffer-Smadja N. Type 1 interferons as a potential treatment against COVID-19. Antiviral Research. 2020;178:104791. https://doi.org/10.1016/j.antiviral.2020.104791.

  • 6.

    Saçar Demirci MD, Adan A. Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection. BioRxiv. 2020:2020.03.15.992438. https://doi.org/10.1101/2020.03.15.992438.

  • 7.

    Frieman M,, Yount B,, Heise M,, Kopecky-Bromberg SA,, Palese P,, Baric RS. Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J Virol. 2007;81(18):9812-24.

  • 8.

    Liu Z, Wang J, Xu Y, Guo M, Mi K, Xu R, et al. Implications of the virus-encoded miRNA and host miRNA in the pathogenicity of SARS-CoV-2. Arxiv. 2020.