MSC–extracellular vesicle microRNAs target host cell-entry receptors in COVID-19 : in silico modeling for in vivo validation

The authors acknowledge technical and financial support from the Ministry of Education and the University of Hafr Al Batin, Saudi Arabia. The authors also thank AlMaarefa University, Riyadh, Saudi Arabia, for supporting this research.Peer reviewe

Exploring the molecular mechanisms of MSC-derived exosomes in Alzheimer's disease : Autophagy, insulin and the PI3K/Akt/mTOR signaling pathway

The authors thank you for acknowledging technical and financial support from the Ministry of Education and the University of Hafr Al Batin, Saudi Arabia. The authors gratefully acknowledge all mothers’ volunteers in the community around the Faculty of Agriculture, Benha University, for their cooperationPeer reviewe

MSC–extracellular vesicle microRNAs target host cell-entry receptors in COVID-19: in silico modeling for in vivo validation

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