Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

Abstract

Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.

Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview

“…Several herbal medicines have been assessed for their anti-SARS-CoV-2 activity either as crude extracts or as purified plant-origin components. Several herbal extracts and components could hinder SARS-CoV-2 replication in vitro and relieve COVID-19 symptoms in vivo in experimental and clinical settings such as Echinacea purpurea extract, Cuphea Ignea extract, Pomegranate Peel extract and juice (Punica Granatum), Clove (Syzygium aromaticum L.), and bioactive polyphenolic compounds, namely curcumin, quercetin, and hesperidin [2,45,[247][248][249][250][251][252][253]. However, the main limitation of the herbal medicines is still the inconsistency of the antiviral efficacy between the cell-based in vitro assays and in vivo experimental settings due to the high hydrophilicity and low oral bioavailability of the herbal medicine components [254].…”

Chemical Composition of Kickxia aegyptiaca Essential Oil and Its Potential Antioxidant and Antimicrobial Activities

“…Kickxia species, including K. aegyptiaca, were documented as significant traditional plants in the treatment of vascular diseases, haemorrhoids, and wounds, along with their uses as laxatives, anti-diabetics, anti-scorbutics, diuretics, and, tonics agents [ 12 , 14 ]. The phytochemical characterization of this plant revealed that it is rich in flavonoids, phenolic acids, glycosides, and iridoids [ 7 , 15 , 16 ]. The different K. aegyptiaca extracts and their isolated metabolites were documented to have antioxidant activity [ 17 , 18 ], larvicidal activity [ 18 ], and cytotoxic activity [ 15 , 19 ].…”

“…The different K. aegyptiaca extracts and their isolated metabolites were documented to have antioxidant activity [ 17 , 18 ], larvicidal activity [ 18 ], and cytotoxic activity [ 15 , 19 ]. Flavonoids, pectolinarigenin, tangeretin, and gardenin were also isolated from K. aegyptiaca, which exhibited potential antiviral activity against SARS-CoV-2 [ 16 ].…”

Inhibition of Respiratory RNA Viruses by a Composition of Ionophoric Polyphenols with Metal Ions

“…Flavonoids, the most common group of polyphenolic compounds in the human diet, are found ubiquitously in fruits and vegetables, and studies support their potential use to treat various human diseases [ 40 , 41 ]. Additionally, flavonoids are considered to have notable beneficial health effects, including antibacterial, anti-inflammatory, antioxidant, and a wide range of antiviral activities against several human viruses [ 15 , 39 , 41 , 42 ]. Hence, flavonoids are key components of various dietary supplements for the relief of medical conditions.…”

“…Based on these considerations, we combined here non-toxic dietary supplements composed of zinc picolinate, copper sulfate, and the flavonoids Epigallocatechin-3-gallate (EGCG), Quercetin, Taxifolin (dihydroquercetin), and Naringenin, that act as zinc ionophores and transport zinc cations through the cell membrane [ 26 , 40 , 42 , 43 , 44 , 45 , 46 , 47 ]. The combination effectively inhibited in vitro viral replication in several cell types, including human lung cells.…”