PT  - JOURNAL ARTICLE
AU  - Jae Hyun Park
AU  - Yuri Choi
AU  - Chul-Woo Lim
AU  - Ji-Min Park
AU  - Shin-Hye Yu
AU  - Yujin Kim
AU  - Hae Jung Han
AU  - Chun-Hyung Kim
AU  - Young-Sook Song
AU  - Chul Kim
AU  - Jisook Moon
TI  - Antiviral effects of miRNAs in extracellular vesicles against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mutations in SARS-CoV-2 RNA virus
AID  - 10.1101/2020.07.27.190561
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.27.190561
4099  - http://biorxiv.org/content/early/2020/07/27/2020.07.27.190561.short
4100  - http://biorxiv.org/content/early/2020/07/27/2020.07.27.190561.full
AB  - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus 2019 (COVID-19). No treatment is available. Micro-RNAs (miRNAs) in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are potential novel therapeutic agents because of their ability to regulate gene expression by inhibiting mRNA. Thus, they may degrade the RNA genome of SARS-CoV-2. EVs can transfer miRNAs to recipient cells and regulate conditions within them. MSC-EVs harbor major therapeutic miRNAs that play important roles in the biological functions of virus-infected host cells. Here, we examined their potential impact on viral and immune responses. MSC-EVs contained 18 miRNAs predicted to interact directly with the 3’ UTR of SARS-CoV-2. These EVs suppressed SARS-CoV-2 replication in Vero E6 cells. In addition, five major miRNAs suppressed virus activity in a luciferase reporter assay by binding the 3’ UTR. MSC-EVs showed strong regenerative effects and potent anti-inflammatory activity which may prevent lethal cytokine storms. We confirmed that EVs regulated inflammatory responses by several cell types, including human brain cells that express the viral receptor ACE2, suggesting that the brain may be targeted by SARS-CoV-2. miRNAs in MSC-EVs have several advantages as therapeutic agents against SARS-CoV-2: 1) they bind specifically to the viral 3’ UTR, and are thus unlikely to have side effects; 2) because the 3’ UTR is highly conserved and rarely mutates, MSC-EV miRNAs could be used against novel variants arising during viral replication; and 3) unique cargoes carried by MSC-EVs can have diverse effects, such as regenerating damaged tissue and regulating immunity.Competing Interest StatementThe authors have declared no competing interest.