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MSC-extracellular vesicle microRNAs target host cell-entry receptors in COVID-19: in silico modeling for in vivo
Hajer A Al Saihati1, Arigue A Dessouky2, Rabab F Salim3
1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Albatin, Hafar Al-Batin, Saudi Arabia. hajirsh@uhb.edu.sa.
Background:
Coronavirus disease 2019 (COVID-19) has created a global pandemic with significant morbidity and mortality. SARS-CoV-2 primarily infects the lungs and is associated with various organ complications. Therapeutic approaches to combat COVID-19, including convalescent plasma and vaccination, have been developed. However, the high mutation rate of SARS-CoV-2 and its ability to inhibit host T-cell activity pose challenges for effective treatment. Mesenchymal stem cells (MSCs) and their extracellular vesicles (MSCs-EVs) have shown promise in COVID-19 therapy because of their immunomodulatory and regenerative properties. MicroRNAs (miRNAs) play crucial regulatory roles in various biological processes and can be manipulated for therapeutic purposes.
Objective:
We aimed to investigate the role of lyophilized MSC-EVs and their microRNAs in targeting the receptors involved in SARS-CoV-2 entry into host cells as a strategy to limit infection. In silico microRNA prediction, structural predictions of the microRNA-mRNA duplex, and molecular docking with the Argonaut protein were performed.
Methods:
Male Syrian hamsters infected with SARS-CoV-2 were treated with human Wharton's jelly-derived Mesenchymal Stem cell-derived lyophilized exosomes (Bioluga Company)via intraperitoneal injection, and viral shedding was assessed. The potential therapeutic effects of MSCs-EVs were measured via histopathology of lung tissues and PCR for microRNAs.
Results:
The results revealed strong binding potential between miRNA‒mRNA duplexes and the AGO protein via molecular docking. MSCs-EVs reduced inflammation markers and normalized blood indices via the suppression of viral entry by regulating ACE2 and TMPRSS2 expression. MSCs-EVs alleviated histopathological aberrations. They improved lung histology and reduced collagen fiber deposition in infected lungs.
Conclusion:
We demonstrated that MSCs-EVs are a potential therapeutic option for treating COVID-19 by preventing viral entry into host cells.
Insights
Mesenchymal stem cell-derived extracellular vesicles (MSCs-EVs) show promise in treating COVID-19 by blocking SARS-CoV-2 entry into cells. These EVs reduce inflammation and improve lung tissue in infected hamsters, offering a potential therapeutic strategy.
Area of Science:
- Biomedical research
- Stem cell therapy
- Virology
Background:
- Coronavirus disease 2019 (COVID-19) poses significant global health challenges due to high morbidity and mortality.
- The SARS-CoV-2 virus primarily targets the lungs, leading to various organ complications.
- Existing COVID-19 therapies face challenges from viral mutation and immune evasion; Mesenchymal stem cells (MSCs) and their extracellular vesicles (MSCs-EVs) offer potential due to immunomodulatory and regenerative properties.
Purpose of the Study:
- To investigate the therapeutic potential of lyophilized MSC-EVs and their microRNAs in inhibiting SARS-CoV-2 entry into host cells.
- To analyze the in silico microRNA-mRNA interactions and molecular docking with the Argonaut protein.
Main Methods:
- Male Syrian hamsters infected with SARS-CoV-2 were treated with human Wharton's jelly-derived MSC-EVs via intraperitoneal injection.
- Viral shedding was assessed, and therapeutic effects were evaluated through histopathology of lung tissues and PCR analysis for microRNAs.
- In silico methods included microRNA prediction, duplex structural predictions, and molecular docking with the AGO protein.
Main Results:
- Molecular docking confirmed strong binding potential between miRNA-mRNA duplexes and the AGO protein.
- MSCs-EV treatment reduced inflammation markers and normalized blood indices by suppressing viral entry through regulation of ACE2 and TMPRSS2 expression.
- Histopathological analysis showed alleviated lung damage, improved lung histology, and reduced collagen fiber deposition in treated hamsters.
Conclusions:
- Lyophilized MSC-EVs demonstrate significant potential as a therapeutic strategy for COVID-19.
- MSCs-EVs effectively prevent viral entry into host cells, offering a novel approach to combat SARS-CoV-2 infection.
- The study highlights MSC-EVs as a promising therapeutic option for managing COVID-19 complications.
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