microRNA-Based Vaccination and Treatment for COVID-19

Shaimaa Abdel-Ghany1, Hussein Sabit2* 

1 Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza, Egypt
2 Department of Genetics, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia

CitationCitation COPIED

Abdel-Ghany S, Sabit H. microRNABased Vaccination and Treatment for COVID-19. Curr Trends Vaccine Vaccinol. 2020 Apr;3(1):109

© 2020 Abdel-Ghany S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 international License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Coronavirusdisease (Coronavirus Disease 2019, COVID-19) is an emerging transmissible disease that was first reported in Wuhan, China, in December 2019 as beta coronavirus. As of April 9, 2020, about 1,569,849 confirmed cases have been documented globally with over 92,191 deaths. COVID-19 is communicated by inhalation or contact with respiratory droplets of infected individuals. Generally, COVID-19 is mild in most cases, even though it might worsen to pneumonia, acute respiratory distress syndrome (ARDS), and multi organ dysfunction in the elderly people. COVID-19 has become a global life-threatening disease. We propose a novel approach to control SARS-CoV-2 viral infection which is based on miRNA.


SARS-CoV-2; Coronavirus; vaccine; Therapeutic treatment, rAAV


Similar to SARS-CoV, COVID-19 uses the angiotensin-converting enzyme 2 (ACE2) as a cell entry receptor to enter the cells by endocytosis, while other CoVs such as MERS-CoV uses the dipeptidyl peptidase 4 (DPP4) host cell receptor as an entry point [1]. A recent molecular dynamics simulation revealed that compared to other CoVs (SARS-CoV and HCoV-NL63), the spike protein–ACE2 receptor interaction contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations in COVID-19 [2]. ACE2 plays a critical role in the renin angiotensin system (RAS), and the discrepancy of ACE/Ang II/AT1R and ACE2/Ang (1-7)/Mas receptor may lead to develop inflammatory response. In addition, elevated ACE and Ang II are bad prognosis for severe pneumonia [3]. Whether COVID-19 can attack neurological tissues expressing ACE2 still needs intensive research [4]. Currently there are little data on the availability of approved therapeutics option for the recently emerged COVID-19. This situation presses researchers over the globe to develop new vaccines or therapeutic molecules to combat this severe virus. For the sake of developing novel drugs, the COVID-19 main protease was made publicly available to facilitate attaining this goal.

miRNA MicroRNAs (miRNAs) are short non-coding RNA fragments involved in post-transcriptional regulation of gene expression [5-7]. In physiological conditions, miRNAs regulate a kaleidoscope of biological pathways including cell differentiation, proliferation and survival [8-10]. miRNA is a regulatory mechanism by which cells can eliminate undesired or malformed mRNA.

Based on this phenomenon, we propose that using in vitroconstructed miRNA specific to SARS-CoV-2 RNA genome will destroy the viral RNA and protect lung cells from being inflamed. Establishing a vaccine and/or therapeutic intervention for this virus is an international goal.

Discussion and Conclusion

Human adeno-associated virus (AAV) are a frequent cause of upper respiratory infections, and therefore, it can be used as delivery vehicles for several lung diseases. It has a single-stranded approximately 4.7kb genome. Recombinant AAV (rAAV) is constructed by replacing the viral cap and rep genes with the desired transgene along with promoter and polyadenylation sequences [11]. These rAAV are extensively characterized as molecular tools with a high safety profile. Generally, rAAV-mediated miRNA inhibition or overexpression of target mRNA provides a simple, efficient way to control the subsequent processing of such mRNA [12]. Long term expression of the cassette harbored by AAV has been reported in several studies on pigs [13], sheep [14], mice [15,16], and human [17,18].

We postulate constructing an AAV with an insert that encodes for miRNA (20-22 nt) specific to a conserved region of the SARS-CoV-19 genome in the 3′ end. This region (about 10, 000 kb) is encoding for the S, E, M, and N functional proteins of the virus. Specific miRNA(s) can be designed to attack one or all of these segments and, using the host cell’ RISC machinery, the target sequence will be destroyed.

This approach enables us to design either a vaccine, with long term expression, or a therapeutic treatment that can be used for patients already contacted the infection. Furthermore, given this approach is successful, it could be employed to future RNA viral attacks (Figure 1).

Figure 1: Graphical representation of the idea


  1. Cui J, Eden JS, Holmes EC, Wang LF. Adaptive evolution of batdipeptidyl peptidase 4 (dpp4): implications for the origin andemergence of Middle East respiratory syndrome coronavirus.Virol J. 2013 Oct;10:304. 
  2. Brielle ES, Schneidman-Duhovny D, Linial M. The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor. BioRxiv. 2020. 
  3. Sun ML, Yang JM, Sun YP, Su GH. [Inhibitors of RAS Might Be aGood Choice for the Therapy of COVID-19 Pneumonia]. ZhonghuaJie He He Hu Xi Za Zhi. 2020 Feb;43(3):219-222. 
  4. Baig AM, KhaleeqUsman A, Syeda A. Evidence of the COVID-19Virus Targeting the CNS: Tissue Distribution, Host-VirusInteraction, and Proposed Neurotropic Mechanisms. ACS ChemNeurosci. 2020. 
  5. Oda S, Takeuchi M, Akai S, Shirai Y, Tsuneyama K, et al. miRNAin Rat Liver Sinusoidal Endothelial Cells and Hepatocytes andApplication to Circulating Biomarkers that Discern Pathogenesisof Liver Injuries. Am J Pathol. 2018 Apr;188(4):916-928. 
  6. Anthiya S, Griveau A, Loussouarn C, Baril P, Garnett M, et al.MicroRNA-Based Drugs for Brain Tumors. Trends in Cancer. 2018Mar;4(3):222-238. 
  7. Kavitha N, Vijayarathna S, Shanmugapriya, Oon CE, Chen Y, et al.MicroRNA profiling in MDA-MB-231 human breast cancer cellexposed to the Phaleria macrocarpa (Boerl.) fruit ethyl acetatefraction (PMEAF) through IIlumina Hi-Seq technologies andvarious in silico bioinformatics tools. J Ethnopharmacol. 2018Mar 1;213:118-131. 
  8. Das S, S. Ghosal. Alteration of MicroRNA Biogenesis Pathways inCancers, in Cancer and Noncoding RNAs, D.J. Chakrabarti and D.S.Mitra, Editors. 2018, Academic Press: Boston. p. 47-58. 
  9. Inácio DP, Amado T, Silva-Santos B, Gomes AQ. Control of T celleffector functions by miRNAs. Cancer Letters, 2018 Jul;427:63-73. 
  10. Balmayor, ER, S. Font Tellado, M. van Griensven, 2.26 MicroRNAas Biomaterial, in Comprehensive Biomaterials II, P. Ducheyne,Editor. 2017, Elsevier: Oxford. p. 558-570. 
  11. Gruntman AM, Mueller C, Flotte TR, Gao G. Gene transfer in thelung using recombinant adeno-associated virus. Curr ProtocMicrobiol. 2012 Aug;Chapter 14:Unit14D.2. 
  12. Xie J, Burt DR, Gao G. Adeno-associated virus-mediated microRNAdelivery and therapeutics. Seminars in liver disease, 2015Jan;35(1):81-88. 
  13. Steines B, Dickey D,Bergen J, Excoffon K, Weinstein JR, et al.CFTR gene transfer with AAV improves early cystic fibrosis pigphenotypes. JCI Insight. 2016 Sep:1(14):e88728. 
  14. McClain LE, Davey MG, Zoltick PW, Limberis MP, Flake AW, et al.Vector serotype screening for use in ovine perinatal lung genetherapy. J Pediatr Surg. 2016 Jun;51(6):879-884. 
  15. Larsen LA, Kauppinen S, Schratt G. Recombinant adenoassociated virus-mediated microRNA delivery into the postnatalmouse brain reveals a role for miR-134 in dendritogenesis invivo. Frontiers in Neural Circuits, 2010 Jan;3(16). 
  16. Pourshafie N, Lee PR, Chen KL, Harmison GG, Bott LC. SystemicDelivery of MicroRNA Using Recombinant Adeno-associatedVirus Serotype 9 to Treat Neuromuscular Diseases in Rodents. JVis Exp. 2018 Aug;(138):55724.
  17. Yang X, Marcucci K, Anguela X,Couto LB. Preclinical Evaluation ofAn Anti-HCV miRNA Cluster for Treatment of HCV Infection. MolTher. 2013 Mar;21(3):588–601. 
  18. Wang F, Fang Q, Chen C, Zhou L, Li H, et al. Recombinant AdenoAssociated Virus-Mediated Delivery of MicroRNA-21-3p LowersHypertension. Mol Ther Nucleic Acids. 2018 Jun;1;11:354-366.