Effective antiviral therapeutics are urgently required to fight severe acute respiratory syndrome (SARS) caused by a SARS coronavirus (SARS-CoV). Because polyphenol catechins could confer antioxidative, anti-inflammatory, antiviral, and antimicrobial activities, we assessed the therapeutic effects of catechins against SARS-CoV replication in Vero E6 cells, the preventive effect of catechins on CD25/CD69/CD94/CD8 + cytotoxic T lymphocytes-mediated adaptive immunity, and the protective effect on lipopolysaccharide-induced acute lung injury (ALI) in mice. We found that catechins containing 32.8% epigallocatechin gallate, 15.2% epicatechin gallate, 13.2 epicatechin, 10.8% epigallocatechin, 10.4% gallocatechin, and 4.4% catechin directly inhibited SARS-CoV replication at sub-micromolecular concentrations. Four-week catechins ingestion increased CD8 + T cell percentage, upregulated CD69 + /CD25 + /CD94-NKG2A/CD8 + T lymphocytes-mediated adaptive immunity, and increased type I cytokines release responding to ovalbumin/alum. Catechins significantly reduced lipopolysaccharide-induced cytokine storm and oxidative stress and ALI by inhibiting PI3K/AKT/mTOR signaling to upregulate Beclin-1/Atg5-Atg12/LC3-II-mediated autophagy mechanism. Pretreatment of autophagy inhibitor 3-Methyladenine reversed the inhibiting effects of catechins on the cytokines and oxidative stress levels and ALI. In conclusion, our data indicated that catechins directly inhibited SARS-CoV replication, potentiated the CD25/CD69/CD94/CD8 + T lymphocytes-mediated adaptive immunity and attenuated lipopolysaccharide-induced ALI and cytokine storm by PI3K/AKT/mTOR-signaling-mediated autophagy, which may be applied to prevent and/or treat SARS-CoV infection.
【저자키워드】 Adaptive immunity, Cytokine storm, autophagy, acute lung injury, catechins, SARS-CoV replication, 【초록키워드】 adaptive, Immunity, Anti-inflammatory, Antiviral, SARS-CoV, cytokine, oxidative stress, CD8, Replication, T cell, mice, Antioxidative, VERO E6 cells, antiviral therapeutics, SARS Coronavirus, catechin, inhibitor, mechanism, protective effect, Signaling, CD69, gallate, acute respiratory syndrome, activities, SARS-CoV infection, therapeutic effect, treat, ingestion, Prevent, concentrations, caused, significantly, indicated, required, inhibited, reduced, against SARS-CoV, upregulated, inhibiting, reversed, inhibiting effect, type I cytokine, 【제목키워드】 catechin, polyphenol, green, tea,