Epigallocatechin Gallate Stabilized by Cyclodextrin Inactivates Influenza Virus and Human Coronavirus 229E

Abstract

Natural products are attractive antiviral agents because they are environment-friendly and mostly harmless. Epigallocatechin gallate (EGCg), a type of catechin, is a well-known natural antiviral agent that can inhibit various viruses. However, EGCg easily oxidizes and loses its physiological activity. Although this problem can be overcome by combining EGCg with cyclodextrin (CD-EGCg), which makes it stable in water at high concentrations, the antiviral effect of this compound remains unclear. Here, we show that in Madin–Darby canine kidney (MDCK) and MRC-5 cells, CD-EGCg is cytotoxic for 50% of cells at 85.61 and 65.34 ppm, respectively. Furthermore, CD-EGCg mainly shows its antiviral effect during the adsorption step for all four influenza virus strains (median effect concentration (EC50) was 0.93 to 2.78 ppm). Its antiviral effect post-adsorption is less intense, and no inhibitory effect is observed on influenza viruses pre-adsorption. Moreover, human coronavirus 229E (HCoV-229E) was inhibited at the adsorption step in short contact (EC50 = 2.5 ppm) and long contact conditions (EC50 = 0.5 ppm) by mixing CD-EGCg with HCoV-229E. These results suggest that CD-EGCg effectively inhibits various viruses that require an adsorption step, and is an effective tool for preventing infection.

Pre-Clinical Evaluation of the Antiviral Activity of Epigalocatechin-3-Gallate, a Component of Green Tea, against Influenza A(H1N1)pdm Viruses

“…Nasal vapour delivery may also bypass the inactivation of EGCG in the gut, improving EGCG bioavailability at the site of infection. Aree and Jongrungruangchok showed that EGCG had improved stability and anti-oxidant properties when combined with cyclodextrin [54]; these findings were recently utilised to demonstrate the antiviral efficacy of the EGCG-cyclodextrin mixture against several influenza viruses in vitro [14]. Interestingly, mouse models used to date have demonstrated the antiviral efficacy of oral EGCG in the absence of drug-stabilising compounds [15,29,35].…”

“…EGCG has also been shown to have antiviral activity against influenza viruses in vitro. Studies have demonstrated a half-maximal inhibitory concentration (IC 50 ) between 5 and 30 µM against several influenza A virus strains, such as A/Puerto Rico/8/1934 (H1N1), A/Hong Kong/1968 (H3N2), and a recent A(H1N1)pdm virus A/Korea/1/09 [11][12][13][14][15][16].…”

“…In vitro activity has also been shown for severe-acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [14,[17][18][19][20], hepatitis C virus (HCV) [21,22], herpes simplex virus (HSV-1), vaccinia virus (VACV), adenovirus (AdV), reovirus (RV) [16], and others. Colpitts and Schang [16] have shown that EGCG interacts with several viruses (HCV, HSV-1, VACV, AdV, RV, and IAV) surface proteins and postulate that inhibition of influenza virus may be due to EGCG binding to the influenza surface glycoprotein haemagglutinin (HA) [16,18,23].…”

Phytochemicals for mitigating the COVID-19 crisis: evidence from pre-clinical and clinical studies

“…EGCG promoted the downregulation of ACE2 receptor and inflammatory factors, IL-1β, IL-6, TNF-α, IFN-α, -β, and -γ expression levels via inhibition of the activity of ROS/hypoxia-inducible factor (HIF)-1α/glycolysis axis in SARS-CoV-2-infected aged patients [60]. It also upregulated HO-1 expression level via stimulation of hepatic Nrf2 activity and decreased ROS generation and IL-6 production via reduction of elevated HIF-1α in COVID-19 infection [61].…”

Cyclodextrins for the Delivery of Bioactive Compounds from Natural Sources: Medicinal, Food and Cosmetics Applications

“…A recent study revealed an enhanced antiviral effect of epigallocatechin gallate, a catechin abundant in tea, against different viruses, e.g., strains of influenza virus and the coronavirus 229E. The compound formed an inclusion complex with a CD mixture composed of 0.1% β-CD, 0.4% γ-CD, and 0.2% ascorbic acid [ 32 ]. The neuroprotective effects of isothiocyanate moringin in an Alzheimer’s disease (AD) in vitro model was reported in another study.…”