| dc.description.abstract | Since the outbreak of COVID-19, over 700 million people worldwide have been infected,
with more than 6 million lives lost. Despite the availability of vaccines and some oral
medications, there are still many post-infection sequelae, which vary in duration from several
weeks to several years depending on the individual. To find an alternative herbal or nutritional
therapy for COVID-19, previous studies have found that green tea epigallocatechin-3-gallate
(EGCG) can effectively inhibit SARS-CoV-2 infection both in vivo and in vitro, and it
suppresses the binding of SARS-CoV-2 spike protein with angiotensin-converting enzyme
(ACE)-2 in the cell-free system. In this study using A549 lung and HepG2 liver cancer cells as
the cell-based systems, we investigated whether EGCG regulates the protein expression and
translocation of ACE2 and type II transmembrane serine protease (TMPRSS2). In A549 cells,
EGCG at 10-80 μM tended to increase ACE2 and TMPRSS2 protein levels after 24 h of
treatment, but it decreased their protein levels at 48 h. Similar effects of EGCG on ACE2 and
TMPRSS2 protein expressions in HepG2 cells were observed at 24 h but not at 48 h. When the
translocation of two proteins were examined at 24 h, the ACE2 was not detected in the plasma
membrane (PM) fraction of A549 cells treated with or without EGCG, but it was increased in
the high-density microsome (HDM) fraction and decreased in the low-density (LDM) fraction
after 24 h of EGCG treatment. However, EGCG was found to dose-dependently increase
TMPRSS2 protein levels in all the fractions. Interestingly, EGCG at 80 μM for 48 h tended to
increase ACE2 protein expression in all fractions but unaltered TMPRSS2 protein levels. In
HepG2 cells, EGCG at 20 and 40 μM but not 80 μM tended to increase ACE2 and TMPRSS2
protein levels in PM and HDM fractions after 24 h of treatment. At 48 h, EGCG tended to
increase ACE2 but not TMPRSS2 proteins in PM, while it unaltered ACE2 proteins and
increased TMPRSS2 in HDM and LDM fractions. These results suggest that EGCG
modulations of ACE2 and TMPRSS2 protein expressions and their translocation from cytosol
to plasma membrane vary with cell types, dose of treatment, and duration of treatment. These
findings may provide the cellular basis for the action of EGCG against the COVID-19 infection
and entry to human lung cells and liver cells. | en_US |