Edible plant-derived exosomal microRNAs: Exploiting a cross-kingdom regulatory mechanism for targeting SARS-CoV-2

Toxicol Appl Pharmacol. 2021 Mar 1:414:115425. doi: 10.1016/j.taap.2021.115425. Epub 2021 Jan 29.


Background: The current COVID-19 pandemic is caused by SARS-CoV-2 which belongs to coronaviridae family. Despite the global prevalence, there are currently no vaccines or drugs. Dietary plant derived exosome-like vesicles are known as edible nanoparticles (ENPs). ENPs are filled with microRNAs (miRNAs), in bioavailable form. Recently, cross-kingdom regulation of human transcripts by plant miRNAs have been demonstrated. However, ENP derived miRNAs targeting SARS-CoV-2 has not been described.

Study design: Mature ENP-derived miRNA sequences were retrieved from small RNA sequencing datasets available in the literature. In silico target prediction was performed to identify miRNAs that could target SARS-CoV-2. ENPs were isolated from ginger and grapefruit plants and the expression of SARS-CoV-2 targeting miRNAs were confirmed by qRT-PCR.

Results: From a total of 260 ENP-derived miRNAs, we identified 22 miRNAs that could potentially target SARS-CoV-2 genome. 11 miRNAs showed absolute target specificity towards SARS-CoV-2 but not SARS-CoV. ENPs from soybean, ginger, hamimelon, grapefruit, tomato and pear possess multiple miRNAs targeting different regions within SARS-CoV-2. Interestingly, osa/cme miR-530b-5p specifically targeted the ribosomal slippage site between ORF1a and ORF1b. We validated the relative expression of six miRNAs (miR-5077, miR-6300, miR-156a, miR-169, miR-5059 and miR-166 m) in ginger and grapefruit ENPs by RT-PCR which showed differential enrichment of specific miRNAs in ginger and grapefruit ENPs.

Conclusion: Since administration of ENPs leads to their accumulation into lung tissues in vivo, ENP derived miRNAs targeting SARS-CoV-2 genome has the potential to be developed as an alternative therapy.

Keywords: COVID-19; Edible nanoparticles; Extracellular vesicles; SARS-CoV-2; microRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Binding Sites
  • COVID-19 Drug Treatment
  • Citrus paradisi / chemistry
  • Computer Simulation
  • Exosomes / chemistry*
  • Genome, Viral
  • Humans
  • MicroRNAs / isolation & purification
  • MicroRNAs / pharmacology*
  • Nanoparticles*
  • Phytochemicals / isolation & purification
  • Phytochemicals / pharmacology*
  • Plants, Edible / chemistry*
  • Plants, Edible / genetics
  • Real-Time Polymerase Chain Reaction
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / genetics*
  • Zingiber officinale / chemistry


  • Antiviral Agents
  • MicroRNAs
  • Phytochemicals