Epigallocatechin Gallate and Isoquercetin Synergize With Remdesivir to Reduce SARS-CoV-2 Replication In Vitro

Abstract

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) urgently needs effective antivirals. After over 2 years since the beginning of the pandemic, only a few FDA approved therapeutic options are available to treat the population. Combination therapies have become a standard for the treatment of other infectious diseases such as HIV and hepatitis C due to their improved efficacy compared to monotherapy, reduced toxicity, the ability to prevent the development of resistant viral strains and their potential to treat co-infection. The interest in identifying molecules displaying bioactivity against SARS-CoV-2 has led to extensive search for promising molecules from the natural pharmacopoeia and polyphenols have been shown to display antiviral activity against a number of viruses including SARS-CoV-2. Here we evaluated the in vitro efficacy of two polyphenols, Epigallocatechin gallate (EGCG) and Isoquercetin, in combination with Remdesivir, the first-approved drug for the treatment of severe COVID-19. We confirmed the inhibitory effects of EGCG and isoquercetin against SARS-CoV-2 and demonstrated their strong antiviral synergistic effects with Remdesivir in vitro. These combinational therapies represent an interesting avenue for the treatment of COVID-19 and grant further studies.

The Potential of Anti-coronavirus Plant Secondary Metabolites in COVID-19 Drug Discovery as an Alternative to Repurposed Drugs: A Review

“…In a separate study, all types of catechins, including ECGC, indicated a considerable affinity to the S protein of the SARS-CoV-2 virus 163 . Moreover, Rabezanahary et al demonstrated the inhibitory effects of EGCG and isoquercetin against SARS-CoV-2 in vitro and proved their substantial antiviral synergistic effects with remdesivir 164 .…”

Computational studies on the interaction of Omicron subvariants (BA.1, BA.2, and BA.3) with ACE2 and polyphenols

“…Similarly, emodin found in rhubarb roots ( Rheum officinale ) showed inhibitory effects by obstructing the SGp–ACE2 interaction in a cell‐free competition assay with an IC 50 of 200 μM 20 . An in vitro study revealed that epigallocatechin‐3‐ O ‐gallate (EGCG) and isoquercetin are potent against SARS‐CoV‐2 and demonstrated synergistic antiviral effects with remdesivir 21 . The use of polyphenols is also a valuable therapeutic strategy to treat COVID‐19 due to their antiviral, antioxidant, antithrombotic, anticancer, antidiabetic, anti‐inflammatory, and prebiotic effects 21–26 .…”

“…20 An in vitro study revealed that epigallocatechin-3-O-gallate (EGCG) and isoquercetin are potent against SARS-CoV-2 and demonstrated synergistic antiviral effects with remdesivir. 21 The use of polyphenols is also a valuable therapeutic strategy to treat COVID-19 due to their antiviral, antioxidant, antithrombotic, anticancer, antidiabetic, antiinflammatory, and prebiotic effects. [21][22][23][24][25][26] Naturally occurring polyphenols are easily accessible and inexpensive to produce and have low toxicity, making them potential drug candidates for treating virus-induced inflammatory diseases.…”

“…21 The use of polyphenols is also a valuable therapeutic strategy to treat COVID-19 due to their antiviral, antioxidant, antithrombotic, anticancer, antidiabetic, antiinflammatory, and prebiotic effects. [21][22][23][24][25][26] Naturally occurring polyphenols are easily accessible and inexpensive to produce and have low toxicity, making them potential drug candidates for treating virus-induced inflammatory diseases. Protease inhibitors have been developed from polyphenols to stop the spread of viruses that cause diseases such as HIV-AIDS, MERS, and SARS.…”

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

“…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].…”