Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2

Abstract

Outbreak of coronavirus disease 2019 occurred in Wuhan and has rapidly spread to almost all parts of world. GB-1, the herbal formula from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, is used for the prophylaxis of SARS-CoV-2 in Taiwan. In this study, we investigated that the effect of GB-1 and the index compounds of GB-1 on the ACE2 and TMPRSS2 expression through in vitro and in vivo study. In our result, GB-1 can inhibit ACE2 and TMPRSS2 protein expression in HepG2 cells, 293T cells, and Caco-2 cells without cytotoxicity. For the mouse model, GB-1 treatment could decrease ACE2 and TMPRSS2 expression levels of the lung and kidney tissue without adverse effects, including nephrotoxicity and hepatotoxicity. In the compositions of GB-1, 0.5–1 mg/ml of Glycyrrhiza uralensis Fisch. ex DC. extract could not inhibit ACE2 mRNA and protein expression in HepG2 cells. In addition, theaflavin-3-gallate could inhibit protein expression of ACE2 and TMPRSS2 without significant cytotoxicity. Our results suggest that GB-1 and theaflavin-3-gallate could act as potential candidates for prophylaxis or treatment of SARS-CoV-2 infection through inhibiting protein expression of ACE2 and TMPRSS2 for the further study.

Food Enrichment with Glycyrrhiza glabra Extract Suppresses ACE2 mRNA and Protein Expression in Rats—Possible Implications for COVID-19

“…There are several review articles suggesting potential positive action of natural products on both prevention and treatment of the disease induced by SARS-CoV-2 [ 4 , 31 , 32 , 33 , 34 , 35 , 36 ]. With respect to supporting experimental evidence, effects of Glycyrrhiza glabra root extract on ACE2 expression have not been reported so far but the present data are consistent with the action of an extract of another plant, namely Glycyrrhiza uralensis, in the lung tissue of mice [ 37 ]. Other supporting data show that extract of Glycyrrhiza glabra or its main components may affect affinity interactions with ACE2 and/or viral proteases [ 38 , 39 , 40 ].…”

Epipharyngeal Abrasive Therapy Down-regulates the Expression of SARS-CoV-2 Entry Factors ACE2 and TMPRSS2

“…SARS-CoV-2 enters human cells via binding to ACE2, followed by its priming by TMPRSS2 (8). Therefore, these proteins are potential targets for antiviral intervention for the prevention of SARS-CoV-2 infection or in related treatment (9). In one study, TMPRSS2 inhibitor was not found to be effective at preventing SARS-CoV-2 infection (10), suggesting that targeting TMPRSS2 alone is not critical for preventing viral infection.…”

Discovery of Highly Potent Fusion Inhibitors with Potential Pan-Coronavirus Activity That Effectively Inhibit Major COVID-19 Variants of Concern (VOCs) in Pseudovirus-Based Assays

“…We found that 293T/ACE2 cells expressed higher levels of TMPRSS2 respect to HT1080/ACE2 and A549/ACE2, but we could not find a direct correlation between expression levels of TMPRSS2 and potency of the inhibitors. Variable expression of TMPRSS2 in different cell lines used for measuring antiviral potency has been reported [62][63][64][65]. The cytotoxicity (CC 50 ) of the small molecules was assessed in parallel with their inhibitory activities (Table 1) for use in determining the SI values.…”