An In Silico Investigation of Brazilian Green Propolis Extracts as Potential Treatment for COVID-19
Jeronimo Geraldo Ferreira Júnior, Janaína Brandão Seibert, Viviane Martins Rebello Dos Santos, Lucas Resende Dutra Sousa, Tatiane Roquete Amparo, Vagner Thalita Marcolan Valverde, Vagner Rodrigues Santos, Junnia Alvarenga De Carvalho Oliveira, Paula Melo De Abreu Vieira, Vagner De Oliveira Machado, Ângela Leão Andrade
ACS Omega, doi:10.1021/acsomega.5c02121
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 immunepromotion 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 (IC 50 values of 18.0 ± 0.3 and 16.6 ± 0.5 μg mL -1 ) and ABTS (IC 50 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 dosedependent 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.
Notes The authors declare no competing financial interest.
References
Anjum, Ullah, Khan, Attaullah, Khan et al., Composition and functional properties of propolis (bee glue): A review, Saudi J. Biol. Sci,
doi:10.1016/j.sjbs.2018.08.013Arnao, Some methodological problems in the determination of antioxidant activity using chromogen radicals: a practical case, Trends Food Sci. Technol,
doi:10.1016/S0924-2244(01)00027-9Arya, Das, Prashar, Kumar, Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs, ChemRxiv,
doi:10.26434/chemrxiv.11860011.v2Azevedo, Seibert, Amparo, Dos Santos Antunes, Sousa et al., Chemical constituents, antioxidant potential, antibacterial study and photoprotective activity of Brazilian corn silk extract, Food Sci. Technol,
doi:10.1590/fst.98421Bachevski, Damevska, Simeonovski, Dimova, Back to the basics: Propolis and COVID-19, Dermatol. Ther,
doi:10.1111/dth.13780Biscaia, Ferreira, Propolis extracts obtained by low pressure methods and supercritical fluid extraction, J. Supercrit. Fluids,
doi:10.1016/j.supflu.2009.07.011Cottica, Sawaya, Eberlin, Franco, Zeoula et al., Antioxidant activity and composition of propolis obtained by different methods of extraction, J. Braz. Chem. Soc,
doi:10.1590/S0103-50532011000500016Cunha, Sawaya, Caetano, Shimizu, Marcucci et al., Factors that influence the yield and composition of Brazilian propolis extracts, J. Braz. Chem. Soc,
doi:10.1590/S0103-50532004000600026Ding, He, Zhang, Huang, Che et al., Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways, J. Pathol,
doi:10.1002/path.1560Elkhenany, El-Badri, Dhar, Green propolis extract promotes in vitro proliferation, differentiation, and migration of bone marrow stromal cells, Biomed. Pharmacother,
doi:10.1016/j.biopha.2019.108861Falcaõ, Vilas-Boas, Estevinho, Barros, Domingues et al., Phenolic characterization of Northeast Portuguese propolis: Usual and unusual compounds, Anal. Bioanal. Chem,
doi:10.1007/s00216-009-3232-8Ferri, Gianotti, Tassoni, Optimisation of assay conditions for the determination of antioxidant capacity and polyphenols in cereal food components, J. Food Compos. Anal,
doi:10.1016/j.jfca.2013.02.004Floegel, Kim, Chung, Koo, Chun, Comparison of ABTS/DPPH assays to measure antioxidant capacity in popular antioxidant-rich US foods, J. Food Compos. Anal,
doi:10.1016/j.jfca.2011.01.008González-Buŕquez, González-Díaz, García-Tovar, Carrillo-Miranda, Soto-Zárate et al., Comparison between in vitro antiviral effect of Mexican propolis and three commercial flavonoids against Canine Distemper virus. Evidence-Based Complementary, Altern. Med,
doi:10.1155/2018/7092416Green, Wagner, Gloglowski, Skipper, Wishnok et al., Analysis of nitrate, nitrite, and ( 15 N)-nitrate in biological fluids, Anal. Biochem,
doi:10.1016/0003-2697(82)90118-XGómez-Caravaca, Gómez-Romero, Arráez-Román, Segura-Carretero, Fernández-Gutiérrez, Advances in the analysis of phenolic compounds in products derived from bees, J. Pharm. Biomed. Anal,
doi:10.1016/j.jpba.2006.03.002Hoffmann, Kleine-Weber, Schroeder, Kruger, Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell,
doi:10.1016/j.cell.2020.02.052Hu, Jiang, Qi, Bai, Ye et al., Races of small molecule clinical trials for the treatment of COVID-19: An up-to-date comprehensive review, Drug Dev. Res,
doi:10.1002/ddr.21895Karki, Sharma, Tuladhar, Williams, Zalduondo et al., Synergism of TNF-α and IFN-γ Triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes, Cell,
doi:10.1016/j.cell.2020.11.025Kon, Rai, None
Kubiliene, Laugaliene, Pavilonis, Maruska, Majiene et al., Alternative preparation of propolis extracts: comparison of their composition and biological activities, BMC Complementary Med. Ther,
doi:10.1186/s12906-015-0677-5Lew, Tsai, Wang, Dengue outbreaks in Hawaii after WWIIa review of public health response and scientific literature, Hawaii J Med Public Health
Li, Zhang, Yao, Chen, Wang et al., The association of postembryo transfer SARS-CoV-2 infection with early pregnancy outcomes in in vitro fertilization: a prospective cohort study, Am. J. Obstet. Gynecol,
doi:10.1016/j.ajog.2023.12.022Machado, Silva, Barreto, Costa, Silva et al., Chemical composition and biological activity of extracts obtained by supercritical extraction and ethanolic extraction of brown, green and red propolis derived from different geographic regions in Brazil, PLoS One,
doi:10.1371/journal.pone.0145954Martinez-Rodriguez, Tavarez, Gonzalez-Sanchez, In vitro toxicity assessment of zinc and nickel ferrite nanoparticles in human erythrocytes and peripheral blood mononuclear cell, Toxicol. in Vitro,
doi:10.1016/j.tiv.2019.02.011Mosmann, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, J. Immunol. Methods,
doi:10.1016/0022-1759(83)90303-4Moura, Negri, Salatino, Lima, Dourado et al., Aqueous extract of Brazilian green propolis: primary components, evaluation of inflammation and wound healing by using subcutaneous implanted sponges. Evidence-Based Complementary, Altern. Med,
doi:10.1093/ecam/nep112Oldoni, Oliveira, Andolfatto, Karling, Calegari et al., Chemical characterization and optimization of the extraction process of bioactive compounds from propolis produced by selected bees Apis mellifera, J. Braz. Chem. Soc,
doi:10.5935/0103-5053.20150186Pascoal, Feás, Dias, Dias, Estevinho, The role of honey and propolis in the treatment of infected wounds, Microbiology for surgical infections: Diagnosis, Prognosis and Treatment
Pasupuleti, Sammugam, Ramesh, Gan, Honey, propolis, and royal jelly: A comprehensive review of their biological actions and health benefits, Oxid. Med. Cell Longevity,
doi:10.1155/2017/1259510Paviani, Fiorito, Sacoda, Cabral, Different solvents for extraction of Brazilian green propolis: composition and extraction yield of phenolic compounds
Pazin, Monaco, Soares, Miguel, Berretta et al., Antioxidant activities of three stingless bee propolis and green propolis types, J. Apic. Res,
doi:10.1080/00218839.2016.1263496Pellegrini, Proteggente, Pannala, Yang, Rice-Evans, Antioxidant activity applying an improved ABTS radical cation decolorization assay, Free Radicals Biol. Med,
doi:10.1016/S0891-5849(98)00315-3Peter, Picoli, Zani, Latosinski, Lima et al., Atividade antiviral e virucida de extratos hidroalcooĺicos de proṕolis marrom, verde e de abelhas Jatai ́(Tetragonisca angustula) frente ao herpersvi ́rus bovino tipo 1 (BoHV-1) e ao vi ́rus da diarreia viral bovina (BVDV), Pesq. Vet. Bras,
doi:10.1590/s0100-736x2017000700003Possas, Lourenco-De-Oliveira, Tauil, Pinheiro, Pissinatti et al., Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation, Mem. Inst. Oswaldo Cruz,
doi:10.1590/0074-02760180278Qin, Zhou, Hu, Zhang, Yang et al., Dysregulation of immune response in patients with COVID-19 in Wuhan, China, Clin. Infect. Dis,
doi:10.1093/cid/ciaa248Ratia, Saikatendu, Santarsiero, Barretto, Baker et al., Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme, Proc. Natl. Acad. Sci. U.S.A,
doi:10.1073/pnas.0510851103Reboucas-Silva, Amorim, Jesus-Santos, De Lima, Lima et al., Leishmanicidal and immunomodulatory properties of Brazilian green propolis extract (EPP-AF®) and a gel formulation in a pre-clinical model, Front. Pharmacol,
doi:10.3389/fphar.2023.1013376Refaat, Mady, Sarhan, Rateb, Alaaeldin, Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19, Int. J. Pharm,
doi:10.1016/j.ijpharm.2020.120028Ripari, Sartori, Honorio, Conte, Tasca et al., Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment, J. Pharm. Pharmacol,
doi:10.1093/jpp/rgaa067Salatino, Fernandes-Silva, Righi, Salatino, Propolis research and the chemistry of plant products, Nat. Prod. Res,
doi:10.1039/c0np00072hSeibert, Bautista-Silva, Amparo, Petit, Pervier et al., Development of propolis nanoemulsion with antioxidant and antimicrobial activity for use as a potential natural preservative, Food Chem,
doi:10.1016/j.foodchem.2019.02.078Semret, Schiller, Jardin, Frenette, Loo et al., Multiplex respiratory virus testing for antimicrobial stewardship: a prospective assessment of antimicrobial use and clinical outcomes among hospitalized adults, J. Infect. Dis,
doi:10.1093/infdis/jix288Silveira, Jong, Berretta, Galvaõ, Ribeiro et al., Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial, Biomed. Pharmacother,
doi:10.1016/j.biopha.2021.111526Sousa, Duarte, Xavier, Das Merceŝ, Vieira et al., Benznidazole-loaded polymeric nanoparticles for oral chemotherapeutic treatment of Chagas disease, Pharmaceutics,
doi:10.3390/pharmaceutics16060800Stebbing, Phelan, Griffin, Tucker, Oechsle et al., COVID-19: combining antiviral and antiinflammatory treatments, Lancet Infect. Dis,
doi:10.1016/S1473-3099(20)30132-8Teixeira, Message, Negri, Salatino, Stringheta, 02121 ACS Omega XXXX, XXX, XXX-XXX N activity of Brazilian propolis samples. Evidence-Based Complementary,
doi:10.1093/ecam/nem177Toreti, Sato, Pastore, Park, Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evidence-Based Complementary, Altern. Med,
doi:10.1155/2013/697390Upton, Cooki, Dictionary of Statistics
Vilas Boas, Campos, Berlanda, De Carvalho Neves, Franco, Antiviral peptides as promising therapeutic drugs, Cell. Mol. Life Sci,
doi:10.1007/s00018-019-03138-wWan, Shang, Graham, Baric, Li, Receptor recognition by the novel coronavirus from wuhan: an analysis based on decade-long structural studies of SARS Coronavirus, J. Virol,
doi:10.1128/JVI.00127-20Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res,
doi:10.1038/s41422-020-0282-0Wozniak, Sip, Mrówczynska, Broniarczyk, Waskiewicz et al., Biological activity and chemical composition of propolis from various regions of Poland, Molecules,
doi:10.3390/molecules28010141Xu, Ikeda, Kobayakawa, Ikami, Kayano et al., Downregulation of Rac1 activation by caffeic acid in aortic smooth muscle cells, Life Sci,
doi:10.1016/j.lfs.2004.11.015Yamaya, Nishimura, Deng, Sugawara, Watanabe et al., Inhibitory effects of glycopyrronium, formoterol, and budesonide on coronavirus HCoV-229E replication and cytokine production by primary cultures of human nasal and tracheal epithelial cells, Respir. Invest,
doi:10.1016/j.resinv.2019.12.005Yuan, Chang, Liu, Wang, Liu et al., Brazilian green propolis inhibits ox-ldl-stimulated oxidative stress in human umbilical vein endothelial cells partly through pi3k/akt/mtormediated nrf2/ho-1 pathway. Evidence-Based Complementary, Altern. Med,
doi:10.1155/2019/5789574Zhang, Shen, Chen, Jiang, Hu, Identification of free radical scavengers from Brazilian green propolis using off-line HPLC-DPPH assay and LC-MS, Food Chem,
doi:10.1111/1750-3841.13730Zhong, Zhao, Peng, Zou, Yang, Recent advances in small-molecular therapeutics for COVID-19, Precision Clinic. Med,
doi:10.1093/pcmedi/pbac024Zhou, Li, Yu, Gu, Pan et al., Dermatophagoides pteronyssinus allergen Der p 22: Cloning, expression, IgE-binding in asthmatic children, and immunogenicity, Pediatr. Allergy Immunol,
doi:10.1111/pai.13835Zhu, Lu, Xu, Chen, Yang et al., Arbidol monotherapy is superior to lopinavir/ritonavir in treating COVID-19, J. Infect,
doi:10.1016/j.jinf.2020.03.060Zhu, Zhang, Wang, Li, Yang et al., China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, N Engl J. Med,
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