Abstract
Propolis, a resin produced by honeybees, has long been used as a dietary supplement and folk remedy, and more recent preclinical investigations have demonstrated a large spectrum of potential therapeutic bioactivities, including antioxidant, antibacterial, anti-inflammatory, neuroprotective, immunomodulatory, anticancer, and antiviral properties. As an antiviral agent, propolis and various constituents have shown promising preclinical efficacy against adenoviruses, influenza viruses, respiratory tract viruses, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 300 chemical components have been identified in propolis, including terpenes, flavonoids, and phenolic acids, with the specific constituent profile varying widely according to geographic origin and regional flora. Propolis and its constituents have demonstrated potential efficacy against SARS-CoV-2 by modulating multiple pathogenic and antiviral pathways. Molecular docking studies have demonstrated high binding affinities of propolis derivatives to multiple SARS-CoV-2 proteins, including 3C-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), the receptor-binding domain (RBD) of the spike protein (S-protein), and helicase (NSP13), as well as to the viral target angiotensin-converting enzyme 2 (ACE2). Among these compounds, retusapurpurin A has shown high affinity to 3CLpro (ΔG = −9.4 kcal/mol), RdRp (−7.5), RBD (−7.2), NSP13 (−9.4), and ACE2 (−10.4) and potent inhibition of viral entry by forming hydrogen bonds with amino acid residues within viral and human target proteins. In addition, propolis-derived baccharin demonstrated even higher binding affinity towards PLpro (−8.2 kcal/mol). Measures of drug-likeness parameters, including metabolism, distribution, absorption, excretion, and toxicity (ADMET) characteristics, also support the potential of propolis as an effective agent to combat COVID-19.
Highlights
Propolis is a natural wax-like resin produced by honeybees (Apis mellifera L.) consisting of salivary secretions, wax, pollen, and various plant materials
Holcová et al utilized three different concentrations (0.1%, 0.5%, and 1%) of propolis special extract GH 2002 in a lip balm through a double-blind, randomized dermatological study involving 150 patients infected with Herpes labialis, and all three concentrations of propolis proved to be effective against Herpes labialis (p < 0.0005) for painless incrustation and local pains, but good tolerability was observed with the 0.5% concentration [125]
Propolis is among the few natural remedies that have been utilized for centuries, and modern laboratory investigations have confirmed that the effectiveness of propolis originates from its extracts and derivatives against multiple disease models, including viral infections
Summary
Propolis is a natural wax-like resin produced by honeybees (Apis mellifera L.) consisting of salivary secretions, wax, pollen, and various plant materials. Propolis consists of 50% resin, 30% wax, 10% essential oils, 5% pollen, 2% mineral salts, and an array of nutrients (intermediate metabolites) and bioactive polyphenols, mainly flavonoids, phenolic acids, and various ester and cinnamic acid derivatives [21,22]. Among these include several well described antiviral and immunomodulatory compounds such as kaempferol, p-coumaric acid, apigenin, artepillin C, caffeic acid, and caffeic acid phenyl ester [15,23,24]. Measurements of drug-likeness parameters such as absorption, distribution, metabolism, excretion, and toxicity (ADMET) further support some of these agents as potential anti-SARS-CoV-2 drug candidates, warranting more extensive preclinical and clinical investigation
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