key: cord-0905873-tqlg5bac
authors: Bachevski, Dimitri; Damevska, Katerina; Simeonovski, Viktor; Dimova, Maja
title: Back to the Basics: Propolis and COVID‐19
date: 2020-06-07
journal: Dermatol Ther
DOI: 10.1111/dth.13780
sha: 1e6e35ce96011ff3c6a5947006fc7b980d4a6f4a
doc_id: 905873
cord_uid: tqlg5bac

nan

Propolis (bee glue) is a complex resinous mixture produced by honeybees (Apis mellifera) used by humans since ancient times for its medicinal properties. Substances collected from various plants are mixed with the β-glycosidase enzyme of the honey bee saliva, digested, and added to beeswax to form the final product. Propolis has an important role in hive construction as a waterproof resin; however it also acts as a barrier to yeasts and molds, bacteria, and viruses.

Propolis is a highly complex mixture, containing over 300 chemical moieties, a number of which have documented beneficial health outcomes. The main constituents of propolis include resins, waxes, essential oils, and pollen, as well as various organic compounds, among which are phenolic compounds, flavonoids, terpenes, esters, aromatic aldehydes and alcohols, and several specific antioxidant compounds including beta-carotene, caffeic acid and kaempferol. A new compound isolated from Brazilian green propolis, 3,5-diprenyl-4-hydroxycinnamic acid (artepillin C), may be a key immunomodulatory compound. 7

The biochemical composition of propolis is highly variable, and this variety is significantly affected by the geographical origin, climate, water availability and other environmental factors. It is widely recognized, for example, that propolis from temperate climatic zones are rich in flavonoids, phenolic acids and their esters, while propolis from tropical regions are rich in prenylated benzophenones, diterpenes and flavonoids. 7,8 That being said, all types of propolis possess antimicrobial, anti-neoplastic, anti-inflammatory, antioxidant, hepatoprotective, cariostatic, and immunostimulatory activity. 8

The natural variety of propolis has traditionally been an obstacle in research and a standardizing medical use. 7 It also cannot be used as raw material (Figure 1) , and it must be purified by extraction with solvents.

Be it alcoholic or aqueous, propolis extracts from temperate climate have been shown to possess a potent and broad-spectrum antiviral activity against a diverse panel of viruses such as HSV-1,

A promising pharmacological approach for treatment of COVID-19 is targeting the downstream effectors, such as p21-activated kinases (PAKs). Caffeic acid phenethyl ester (CAPE), one of the most important constituents of propolis, has shown the property to down-regulate RAC (a signaling protein found in human cells), therefore acting as a RAC/CDC42-activated kinase 1 (PAK1) blocker. These data support the idea that CAPE can be useful as an agent to stop or inhibit coronavirus-induced fibrosis in the lungs. 16 Although propolis belongs to the safest natural remedies, on rare occasions, adverse effects of propolis or its constituents are to be expected, especially allergic reactions. Therefore, when used in prevention or treatment of COVID-19, hypersensitivity reactions should be taken into account. 8

Viruses causing respiratory diseases invade their host via the nasopharyngeal, oropharyngeal or tracheal mucosa. At present, there are no specific antiviral drugs or vaccines against SARS-CoV2 infection for potential therapy of humans. Identifying methods able to reduce or prevent colonization, viral adhesion and promote virus shedding on mucous membranes or have the ability to inactivate pathogens and thus reduce virus dose and/or increase immune response would be essential in the management of COVID-19 outbreak. Therefore, we suggest that propolis (or its constituents) may represent a low-cost treatment option that may act as potential inhibitors of SARS-CoV-2 in the oropharyngeal niche.

Propolis should be explored as a prophylaxis in high-risk groups, such as individuals in close contact with infected patients. Further studies should be conducted for the validation of these compounds using in vitro and in vivo models. These studies must thoroughly characterize the biological activities and underlying mechanisms of action and isolating the most beneficial compounds, mainly those related to antiviral properties.

Composition and functional properties of propolis (bee glue): A review

Inhibiting activity of própolis on the influenza virus

Effects of propolis flavonoids on virus infectivity and replication

Severe Acute Respiratory Syndrome Epidemiology and Control

Coronavirus disease 2019 (COVID-19): first indication of efficacy of Gene-Eden-VIR/Novirin in SARS-CoV-2 infection

PAK1-blockers: Potential Therapeutics against COVID-19

Raw propolis cannot be used, and it must be purified by extraction with solvents, to remove the inert material and preserve the polyphenolic fraction