An In Silico Investigation of Brazilian Green Propolis Extracts as Potential Treatment for COVID-19

The absence of a specific antiviral treatment for the highly virulent and lethal coronavirus disease 2019 (Covid-19) remains a significant challenge. The potential of natural agents with immune-promotion capabilities, including apitherapy products, is being investigated as a potential therapeutic modality. Propolis is characterized by a high concentration of bioactive compounds, which exhibit significant antimicrobial, bactericidal, antiviral, anti-inflammatory, immunomodulatory, and antioxidant properties. This study investigated the potential of ethanolic extracts of Brazilian green propolis for COVID-19 treatment. Propolis extracts were obtained at room (EEPV-F) and under 70 °C-heat (EEPV-Q) temperatures, and the extraction yields were 36.74% and 53.54%, respectively. Total flavonoid contents (10.6 ± 0.9 and 6.6 ± 0.2 mg QE g^-1), total phenolic compounds (44 ± 2 and 66 ± 3 mg GAE g^-1), and antioxidant capacity by DPPH (IC₅₀ values of 18.0 ± 0.3 and 16.6 ± 0.5 μg mL^-1) and ABTS (IC₅₀ values of 16.6 ± 0.02 and 15.3 ± 0.2 μg mL^-1) assays were determined. The extracts were not cytotoxic to RAW 264.7 macrophages and exhibited dose-dependent anti-inflammatory activity, particularly EEPV-Q. All EEPV-Q concentrations significantly reduced nitric oxide production and demonstrated suitability for further investigation. Molecular docking analysis revealed that the compound guibourtinidol-(4alpha→8)-epiafzelechin exhibited stronger binding affinity for PLpro, RdRp, and Spike-analyzed enzymes. Both EEPV-F and EEPV-Q presented hemolytic activity below 5% across all tested concentrations. Given the limited therapeutic options available for COVID-19, the utilization of green propolis as a therapeutic agent has emerged as a promising and relevant approach. This natural product possesses several advantages, including its safety, ease of oral administration, and its availability as both a natural supplement and a functional food.