Skip to main content

Advertisement

Log in

Circulating microRNA profile in response to remdesivir treatment in coronavirus disease 2019 (COVID-19) patients

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Coronavirus disease 2019 (COVID-19), a serious infectious disease caused by the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a major global health crisis. Although no specific antiviral drugs have been proven to be fully effective against COVID-19, remdesivir (GS-5734), a nucleoside analogue prodrug, has shown beneficial effects when used to treat severe hospitalized COVID-19 cases. The molecular mechanism underlying this beneficial therapeutic effect is still vaguely understood. In this study, we assessed the effect of remdesivir treatment on the pattern of circulating miRNAs in the plasma of COVID-19 patients, which was analyzed using MiRCURY LNA miRNA miRNome qPCR Panels and confirmed by quantitative real-time RT-PCR (qRT-PCR). The results revealed that remdesivir treatment can restore the levels of miRNAs that are upregulated in COVID-19 patients to the range observed in healthy subjects. Bioinformatics analysis revealed that these miRNAs are involved in diverse biological processes, including the transforming growth factor beta (TGF-β), hippo, P53, mucin-type O-glycan biosynthesis, and glycosaminoglycan biosynthesis signaling pathways. On the other hand, three miRNAs (hsa-miR-7-5p, hsa-miR-10b-5p, and hsa-miR-130b-3p) were found to be upregulated in patients receiving remdesivir treatment and in patients who experienced natural remission. These upregulated miRNAs could serve as biomarkers of COVID-19 remission. This study highlights that the therapeutic potential of remdesivir involves alteration of certain miRNA-regulated biological processes. Targeting of these miRNAs should therefore be considered for future COVID-19 treatment strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Hu B, Guo H, Zhou P, Shi ZL (2021) Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol 19:141–154. https://doi.org/10.1038/s41579-020-00459-7

    Article  CAS  PubMed  Google Scholar 

  2. Mason RJ (2020) Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J. https://doi.org/10.1183/13993003.00607-2020

  3. Hendaus MA (2021) Remdesivir in the treatment of coronavirus disease 2019 (COVID-19): a simplified summary. J Biomol Struct Dyn 39:3787–3792. https://doi.org/10.1080/07391102.2020.1767691

    Article  CAS  PubMed  Google Scholar 

  4. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  5. Kreth S, Hübner M, Hinske LC (2018) MicroRNAs as clinical biomarkers and therapeutic tools in perioperative medicine. Anesth Analg 126:670–681. https://doi.org/10.1213/ANE.0000000000002444

    Article  CAS  PubMed  Google Scholar 

  6. González Plaza JJ (2016) Current roles of microRNAs in infectious diseases—advancing into healthcare. Infektološki glasnik 36:5–15

    Google Scholar 

  7. Fayyad-Kazan M, ElDirani R, Hamade E et al (2019) Circulating miR-29c, miR-30c, miR-193a-5p and miR-885-5p: Novel potential biomarkers for HTLV-1 infection diagnosis. Infect Genet Evol 74:103938. https://doi.org/10.1016/j.meegid.2019.103938

    Article  CAS  PubMed  Google Scholar 

  8. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108

    Article  CAS  PubMed  Google Scholar 

  9. Hardin LT, Xiao N (2022) miRNAs: the key regulator of COVID-19 disease. Int J Cell Biol. https://doi.org/10.1155/2022/1645366

    Article  PubMed  PubMed Central  Google Scholar 

  10. Li C, Hu X, Li L, Li J, hui, (2020) Differential microRNA expression in the peripheral blood from human patients with COVID-19. J Clin Lab Anal. https://doi.org/10.1002/jcla.23590

    Article  PubMed  PubMed Central  Google Scholar 

  11. Fayyad-Kazan M, Makki R, Skafi N et al (2021) Circulating miRNAs: potential diagnostic role for coronavirus disease 2019 (COVID-19). Infect Genet Evol. https://doi.org/10.1016/J.MEEGID.2021.105020

    Article  PubMed  PubMed Central  Google Scholar 

  12. Farr RJ, Rootes CL, Rowntree LC et al (2021) Altered microRNA expression in COVID-19 patients enables identification of SARS-CoV-2 infection. PLoS Pathog 17:e1009759. https://doi.org/10.1371/JOURNAL.PPAT.1009759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Giannella A, Riccetti S, Sinigaglia A et al (2022) Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients. Front Immunol 13:4409. https://doi.org/10.3389/FIMMU.2022.968991/BIBTEX

    Article  Google Scholar 

  14. Panda M, Kalita E, Singh S et al (2022) MiRNA-SARS-CoV-2 dialogue and prospective anti-COVID-19 therapies. Life Sci 305:120761. https://doi.org/10.1016/J.LFS.2022.120761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Aschner Y, Downey GP (2016) Transforming growth factor-B: master regulator of the respiratory system in health and disease. Am J Respir Cell Mol Biol 54:647–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang S, Zhou L, Ling L et al (2020) The crosstalk between Hippo-YAP pathway and innate immunity. Front Immunol 0:323. https://doi.org/10.3389/FIMMU.2020.00323

    Article  Google Scholar 

  17. Ma-Lauer Y, Carbajo-Lozoya J, Hein MY et al (2016) P53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1. Proc Natl Acad Sci USA 113:E5192–E5201. https://doi.org/10.1073/PNAS.1603435113/SUPPL_FILE/PNAS.201603435SI.PDF

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wardzala CL, Wood AM, Belnap DM, Kramer JR (2022) Mucins inhibit coronavirus infection in a glycan-dependent manner. ACS Cent Sci 8:351–360. https://doi.org/10.1021/ACSCENTSCI.1C01369/ASSET/IMAGES/LARGE/OC1C01369_0005.JPEG

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kwon PS, Oh H, Kwon SJ et al (2020) Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro. Cell Discov 6:1–4. https://doi.org/10.1038/s41421-020-00192-8

    Article  CAS  Google Scholar 

  20. Fleseriu M (2021) Pituitary disorders and COVID-19, reimagining care: the pandemic a year and counting. Front Endocrinol (Lausanne) 12:200. https://doi.org/10.3389/FENDO.2021.656025/BIBTEX

    Article  Google Scholar 

  21. Diallo I, Jacob RA, Vion E et al (2023) Altered microRNA transcriptome in cultured human airway cells upon infection with SARS-CoV-2. Viruses 15:496. https://doi.org/10.3390/V15020496/S1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Diallo I, Ho J, Laffont B et al (2021) Altered microRNA transcriptome in cultured human liver cells upon infection with Ebola virus. Int J Mol Sci. https://doi.org/10.3390/IJMS22073792

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Lebanese University.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Mohammad Fayyad-Kazan or Bassam Badran.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures involving human participants were in accordance with the ethical standards of the local ethics committee of the Lebanese University and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Handling Editor: William G Dundon.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fayyad-Kazan, M., Makki, R., Homsi, M.E. et al. Circulating microRNA profile in response to remdesivir treatment in coronavirus disease 2019 (COVID-19) patients. Arch Virol 168, 194 (2023). https://doi.org/10.1007/s00705-023-05825-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00705-023-05825-3

Navigation