Journal Article

Anti-Viral and Immunomodulatory Properties of Propolis: Chemical Diversity, Pharmacological Properties, Preclinical and Clinical Applications, and In Silico Potential against SARS-CoV-2

Zou, Xiaobo, AlAjmi, Mohamed F., El-Seedi, Hesham R., Yosri, Nermeen, Algethami, Ahmed F. M., Moustafa, Mahmoud F., Khalifa, Shaden A. M., Masry, Saad H. D., Abd El-Wahed, Aida A., Afifi, Hanan S., Khattab, Omar M., Guo, Zhiming, Ibrahim, Mahmoud A. A., Sabry, Aya, Ghonaim, Reem

2021

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: 17th century / absorption / ACE2 / Adenoviridae / Adenoviruses / Affinity / Amino acids / Angiotensin / Angiotensin-converting enzyme 2 / Anticancer properties / Antioxidants / antiviral / Antiviral activity / Antiviral agents / Bees / Binding / Biocompatibility / Cardiovascular disease / chemical constituents / Chromatography / clinical applications / Colds / computer simulation / Constituents / Coronaviruses / COVID-19 / COVID-19 infection / Diabetes / Dietary supplements / Disease transmission / DNA helicase / DNA-directed RNA polymerase / Drug metabolism / excretion / Flavonoids / Flora / Food science / Herpes simplex / Herpes viruses / Hippocrates (460?-377? BC) / HIV / Human alphaherpesvirus 1 / Human immunodeficiency virus / humans / hydrogen / Hydrogen bonding / Hydrogen bonds / Immunomodulation / immunomodulatory / Inflammation / Influenza / Mass spectrometry / Medicine / metabolism / Molecular docking / Neuroprotection / NMR / Nuclear magnetic resonance / Papain / Peptidyl-dipeptidase A / Phenolic acids / Phenols / Propolis / Protease / Proteinase / proteinases / Proteins / provenance / Respiratory diseases / respiratory system / Respiratory tract / Review / Rheumatism / RNA-directed RNA polymerase / SARS-CoV-2 / Scientific imaging / Severe acute respiratory syndrome coronavirus 2 / Terpenes / terpenoids / therapeutics / Toxicity / Traditional medicine / Viral diseases / Viral infections / Viruses / Wound healing