Pinostrobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism.

Coronaviruses, as enveloped positive-strand RNA viruses, manipulate host lipid compositions to enable robust viral replication. Temporal modulation of the host lipid metabolism is a potential novel strategy against coronaviruses. Here, the dihydroxyflavone pinostrobin (PSB) was identified through bioassay that inhibited the increment of human coronavirus OC43 (HCoV-OC43) in human ileocecal colorectal adenocarcinoma cells. Lipid metabolomic studies showed that PSB interfered with linoleic acid and arachidonic acid metabolism pathways. PSB significantly decreased the level of 12, 13- epoxyoctadecenoic (12, 13-EpOME) and increased the level of prostaglandin E2. Interestingly, exogenous supplement of 12, 13-EpOME in HCoV-OC43-infected cells significantly stimulated HCoV-OC43 virus replication. Transcriptomic analyses showed that PSB is a negative modulator of aryl hydrocarbon receptor (AHR)/cytochrome P450 (CYP) 1A1signaling pathway and its antiviral effects can be counteracted by supplement of FICZ, a well-known AHR agonist. Integrative analyses of metabolomic and transcriptomic indicated that PSB could affect linoleic acid and arachidonic acid metabolism axis through AHR/CYP1A1 pathway. These results highlight the importance of the AHR/CYP1A1 pathway and lipid metabolism in the anti-coronavirus activity of the bioflavonoid PSB.

Propolis effects in periodontal disease seem to affect coronavirus disease: a meta-analysis.

This meta-analysis aimed to investigate the effects of propolis on the severity of coronavirus disease symptoms by reducing periodontal disease. PubMed, EMBASE, SciELO, Web of Science, and SCOPUS databases were systematically searched. Studies have been conducted analyzing propolis's effects on COVID-19 and periodontitis. The study was conducted according to the PRISMA statement and registered in PROSPERO. Risk of Bias (RoB) assessment and meta-analysis of clinical studies were performed (Review Manager 5, Cochrane). The certainty of the evidence was assessed using GradePro (GDT). Studies have shown propolis flavonoids inhibit viral replication in several DNA and RNA viruses, including coronaviruses. Propolis components have an aminopeptidase inhibitor activity that can inhibit the main proteases of SARS viruses and seem to inhibit protein spikes, which are sites of most mutations in SARS-CoV strains. The meta-analysis showed favorable results with the use of propolis on probing depth (95%CI: 0.92; p < 0.001), clinical attachment level (95%CI: 1.48; p < 0.001), gingival index (95%CI: 0.14; p = 0.03), plaque index (95%CI: 0.11; p = 0.23), and blending on probing (95%CI: 0.39; p < 0.001). The antibacterial activity of propolis could be mediated through its direct action on microorganisms or the stimulation of the immune system, activating natural defenses. Thus, propolis inhibits the replication of SARS-CoV-2 as well as its bacterial activity. Treatment with propolis improves general health and facilitates the activation of the immune system against coronavirus.

Extraction of Antioxidant Compounds from Brazilian Green Propolis Using Ultrasound-Assisted Associated with Low- and High-Pressure Extraction Methods.

The demand for bee products has been growing, especially regarding their application in complementary medicine. Apis mellifera bees using Baccharis dracunculifolia D.C. (Asteraceae) as substrate produce green propolis. Among the examples of bioactivity of this matrix are antioxidant, antimicrobial, and antiviral actions. This work aimed to verify the impact of the experimental conditions applied in low- and high-pressure extractions of green propolis, using sonication (60 kHz) as pretreatment to determine the antioxidant profile in the extracts. Total flavonoid content (18.82 ± 1.15-50.47 ± 0.77 mgQE·g-1), total phenolic compounds (194.12 ± 3.40-439.05 ± 0.90 mgGAE·g-1) and antioxidant capacity by DPPH (33.86 ± 1.99-201.29 ± 0.31 µg·mL-1) of the twelve green propolis extracts were determined. By means of HPLC-DAD, it was possible to quantify nine of the fifteen compounds analyzed. The results highlighted formononetin (4.76 ± 0.16-14.80 ± 0.02 mg·g-1) and p-coumaric acid (

Antiviral Activity of Bee Products.

Honey bees provide many products exerting a wide range of benefits to humans. Honey, propolis, royal jelly, beeswax, bee venom, bee pollen and bee bread have been used as natural medicines since ancient times because of their therapeutic effects. These products have demonstrated healing properties against wounds, diabetes, gastrointestinal diseases, cancer, asthma, neurological diseases, bacterial and viral infections. The antibacterial and antibiofilm activity of honey bee products is widely studied, and a huge body of evidence supports it. On the other hand, their antiviral effect has not been extensively studied. However, recent research has demonstrated their potential against various viral infections including SARS-CoV-2. Hence, honey bee products could be alternatives to treat viral diseases, especially when there is no effective treatment available. This narrative review aims to present up-to-date data (including ongoing clinical trials) regarding the antiviral activity of honey bee products, aiming to elucidate how honey bee product supplementation contributes to antiviral treatment.

The prophylactic efficacy of Anatolian propolis in individuals at high risk of COVID-19.

OBJECTIVE: No prophylactic treatment is available for individuals at high risk of developing COVID-19. This study, which was conducted between December 25, 2020, and January 25, 2021, is one of the first clinical studies to evaluate the efficacy of Anatolian propolis supplement against COVID-19. The aim was to obtain evidence on the prophylactic use of Anatolian propolis in individuals at high risk of developing COVID-19. SUBJECTS AND METHODS: This volunteer-based study was conducted in two centers. The study involved 209 healthcare professionals (physicians, nurses, medical secretaries) from Emergency Medicine Department of Medical Faculty of Ataturk University and Emergency Medicine Department of Rize Recep Tayyip Erdogan University. 204 participants meeting the study criteria were divided into two groups as experimental group and control group. The experimental group received 20 drops of BEE'O UP (BEE&YOU) 30% Propolis drops twice a day during a follow-up period of 1 month. The control group received no supplement but was followed up. The participants showing symptoms during the study and all the participants at the end the study were subjected to PCR testing. RESULTS: The evaluation of the results of PCR testing at the end of the study has shown that 14 participants from the control group and only 2 participants from the experimental group, who received Anatolian propolis supplement, were reported as positive cases. CONCLUSIONS: It has been found that a statistically significant protection was induced against COVID-19 infection in 98% of the experimental group, who received Anatolian propolis, compared to the control group.

The Effects of Propolis on Viral Respiratory Diseases.

Propolis remains an interesting source of natural chemical compounds that show, among others, antibacterial, antifungal, antiviral, antioxidative and anti-inflammatory activities. Due to the growing incidence of respiratory tract infections caused by various pathogenic viruses, complementary methods of prevention and therapy supporting pharmacotherapy are constantly being sought out. The properties of propolis may be important in the prevention and treatment of respiratory tract diseases caused by viruses such as severe acute respiratory syndrome coronavirus 2, influenza viruses, the parainfluenza virus and rhinoviruses. One of the main challenges in recent years has been severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing COVID-19. Recently, an increasing number of studies are focusing on the activity of various propolis preparations against SARS-CoV-2 as an adjuvant treatment for this infection. Propolis has shown a few key mechanisms of anti-SARS-CoV-2 action such as: the inhibition of the interaction of the S1 spike protein and ACE-2 protein; decreasing the replication of viruses by diminishing the synthesis of RNA transcripts in cells; decreasing the particles of coronaviruses. The anti-viral effect is observed not only with extracts but also with the single biologically active compounds found in propolis (e.g., apigenin, caffeic acid, chrysin, kaempferol, quercetin). Moreover, propolis is effective in the treatment of hyperglycemia, which increases the risk of SARS-CoV-2 infections. The aim of the literature review was to summarize recent studies from the PubMed database evaluating the antiviral activity of propolis extracts in terms of prevention and the therapy of respiratory tract diseases (in vitro, in vivo, clinical trials). Based upon this review, it was found that in recent years studies have focused mainly on the assessment of the effectiveness of propolis and its chemical components against COVID-19. Propolis exerts wide-spectrum antimicrobial activities; thus, propolis extracts can be an effective option in the prevention and treatment of co-infections associated with diseases of the respiratory tract.

Propolis: Its Role and Efficacy in Human Health and Diseases.

With technological advancements in the medicinal and pharmaceutical industries, numerous research studies have focused on the propolis produced by stingless bees (Meliponini tribe) and Apis mellifera honeybees as alternative complementary medicines for the potential treatment of various acute and chronic diseases. Propolis can be found in tropical and subtropical forests throughout the world. The composition of phytochemical constituents in propolis varies depending on the bee species, geographical location, botanical source, and environmental conditions. Typically, propolis contains lipid, beeswax, essential oils, pollen, and organic components. The latter include flavonoids, phenolic compounds, polyphenols, terpenes, terpenoids, coumarins, steroids, amino acids, and aromatic acids. The biologically active constituents of propolis, which include countless organic compounds such as artepillin C, caffeic acid, caffeic acid phenethyl ester, apigenin, chrysin, galangin, kaempferol, luteolin, genistein, naringin, pinocembrin, coumaric acid, and quercetin, have a broad spectrum of biological and therapeutic properties such as antidiabetic, anti-inflammatory, antioxidant, anticancer, rheumatoid arthritis, chronic obstruct pulmonary disorders, cardiovascular diseases, respiratory tract-related diseases, gastrointestinal disorders, as well as neuroprotective, immunomodulatory, and immuno-inflammatory agents. Therefore, this review aims to provide a summary of recent studies on the role of propolis, its constituents, its biologically active compounds, and their efficacy in the medicinal and pharmaceutical treatment of chronic diseases.

Perspectives for Uses of Propolis in Therapy against Infectious Diseases.

Propolis has gained wide popularity over the last decades in several parts of the world. In parallel, the literature about propolis composition and biological properties increased markedly. A great number of papers have demonstrated that propolis from different parts of the world is composed mainly of phenolic substances, frequently flavonoids, derived from plant resins. Propolis has a relevant role in increasing the social immunity of bee hives. Experimental evidence indicates that propolis and its components have activity against bacteria, fungi, and viruses. Mechanisms of action on bacteria, fungi, and viruses are known for several propolis components. Experiments have shown that propolis may act synergistically with antibiotics, antifungals, and antivirus drugs, permitting the administration of lower doses of drugs and higher antimicrobial effects. The current trend of growing resistance of microbial pathogens to the available drugs has encouraged the introduction of propolis in therapy against infectious diseases. Because propolis composition is widely variable, standardized propolis extracts have been produced. Successful clinical trials have included propolis extracts as medicine in dentistry and as an adjuvant in the treatment of patients against COVID-19. Present world health conditions encourage initiatives toward the spread of the niche of propolis, not only as traditional and alternative medicine but also as a relevant protagonist in anti-infectious therapy. Production of propolis and other apiary products is environmentally friendly and may contribute to alleviating the current crisis of the decline of bee populations. Propolis production has had social-economic relevance in Brazil, providing benefits to underprivileged people.

The antiviral and immunomodulatory activities of propolis: An update and future perspectives for respiratory diseases.

Propolis is a complex natural product that possesses antioxidant, anti-inflammatory, immunomodulatory, antibacterial, and antiviral properties mainly attributed to the high content in flavonoids, phenolic acids, and their derivatives. The chemical composition of propolis is multifarious, as it depends on the botanical sources from which honeybees collect resins and exudates. Nevertheless, despite this variability propolis may have a general pharmacological value, and this review systematically compiles, for the first time, the existing preclinical and clinical evidence of propolis activities as an antiviral and immunomodulatory agent, focusing on the possible application in respiratory diseases. In vitro and in vivo assays have demonstrated propolis broad-spectrum effects on viral infectivity and replication, as well as the modulatory actions on cytokine production and immune cell activation as part of both innate and adaptive immune responses. Clinical trials confirmed propolis undeniable potential as an effective therapeutic agent; however, the lack of rigorous randomized clinical trials in the context of respiratory diseases is tangible. Since propolis is available as a dietary supplement, possible use for the prevention of respiratory diseases and their deleterious inflammatory drawbacks on the respiratory tract in humans is considered and discussed. This review opens up new perspectives on the clinical investigation of neglected propolis biological properties which, now more than ever, are particularly relevant with respect to the recent outbreaks of pandemic respiratory infections.

Propolis efficacy on SARS-COV viruses: a review on antimicrobial activities and molecular simulations.

This current study review provides a brief review of a natural bee product known as propolis and its relevance toward combating SARS-CoV viruses. Propolis has been utilized in medicinal products for centuries due to its excellent biological properties. These include anti-oxidant, immunomodulatory, anti-inflammatory, anti-viral, anti-fungal, and bactericidal activities. Furthermore, studies on molecular simulations show that flavonoids in propolis may reduce viral replication. While further research is needed to validate this theory, it has been observed that COVID-19 patients receiving propolis show earlier viral clearance, enhanced symptom recovery, quicker discharge from hospitals, and a reduced mortality rate relative to other patients. As a result, it appears that propolis could probably be useful in the treatment of SARS-CoV-2-infected patients. Therefore, this review sought to explore the natural properties of propolis and further evaluated past studies that investigated propolis as an alternative product for the treatment of COVID-19 symptoms. In addition, the review also highlights the possible mode of propolis action as well as molecular simulations of propolis compounds that may interact with the SARS-CoV-2 virus. The activity of propolis compounds in decreasing the impact of COVID-19-related comorbidities, the possible roles of such compounds as COVID-19 vaccine adjuvants, and the use of nutraceuticals in COVID-19 treatment, instead of pharmaceuticals, has also been discussed.

Activity of Propolis Nanoparticles against HSV-2: Promising Approach to Inhibiting Infection and Replication.

Herpes simplex type 2 (HSV-2) infection causes a significant life-long disease. Long-term side effects of antiviral drugs can lead to the emergence of drug resistance. Thus, propolis, a natural product derived from beehives, has been proposed to prevent or treat HSV-2 infections. Unfortunately, therapeutic applications of propolis are still limited due its poor solubility. To overcome this, a nanoparticle-based drug delivery system was employed. An ethanolic extract of propolis (EEP) was encapsulated in nanoparticles composed of poly(lactic-co-glycolic acid) and chitosan using a modified oil-in-water single emulsion by using the solvent evaporation method. The produced nanoparticles (EEP-NPs) had a spherical shape with a size of ~450 nm and presented satisfactory physicochemical properties, including positively charged surface (38.05 ± 7.65 mV), high entrapment efficiency (79.89 ± 13.92%), and sustained release profile. Moreover, EEP-NPs were less cytotoxic on Vero cells and exhibited anti-HSV-2 activity. EEP-NPs had a direct effect on the inactivation of viral particles, and also disrupted the virion entry and release from the host cells. A significant decrease in the expression levels of the HSV-2 replication-related genes (ICP4, ICP27, and gB) was also observed. Our study suggests that EEP-NPs provide a strong anti-HSV-2 activity and serve as a promising platform for the treatment of HSV-2 infections.

Antimicrobial Triterpenoids and Ingol Diterpenes from Propolis of Semi-Arid Region of Morocco.

The chemical composition and antimicrobial activity of propolis from a semi-arid region of Morocco were investigated. Fifteen compounds, including triterpenoids (1, 2, 7-12), macrocyclic diterpenes of ingol type (3-6) and aromatic derivatives (13-15), were isolated by various chromatographic methods. Their structures were elucidated by a combination of spectroscopic and chiroptical methods. Compounds 1 and 3 are new natural compounds, and 2, 4-6, and 9-11 are newly isolated from propolis. Moreover, the full nuclear magnetic resonance (NMR) assignments of three of the known compounds (2, 4 and 5) were reported for the first time. Most of the compounds tested, especially the diterpenes 3, 4, and 6, exhibited very good activity against different strains of bacteria and fungi. Compound 3 showed the strongest activity with minimum inhibitory concentrations (MICs) in the range of 4-64 µg/mL. The combination of isolated triterpenoids and ingol diterpenes was found to be characteristic for Euphorbia spp., and Euphorbia officinarum subsp. echinus could be suggested as a probable and new plant source of propolis.

The use of standardized Brazilian green propolis extract (EPP-AF) as an adjunct treatment for hospitalized COVID-19 patients (BeeCovid2): a structured summary of a study protocol for a randomized controlled trial.

BACKGROUND: The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study aims to assess whether EPP-AF has an impact on the improvement of patients hospitalized with COVID-19 by reducing the length of hospital stay. METHODS: BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 and up to 14 days of symptoms were included. Patients under mechanical ventilation at randomization, pregnant women, cancer patients, transplanted or using immunosuppression, HIV patients, patients who used propolis in the last 30 days, bacterial or fungal infection at randomization, impossibility of using medication orally or enterally, and advanced chronic diseases (e.g., advanced heart failure, severe liver disease, and end-stage chronic kidney disease). Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the difference in length of hospital stay in days between groups. Secondary outcomes include the need for mechanical ventilation, the rate of secondary infection, rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO). DISCUSSION: This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04800224 . Registered on March 16, 2021.

Potential effects of propolis and honey in COVID-19 prevention and treatment: A systematic review of in silico and clinical studies.

BACKGROUND: Propolis and honey have been studied as alternative treatments for patients with coronavirus disease 2019 (COVID-19). However, no study has yet summarized the full body of evidence for the use of propolis and honey in COVID-19 prevention and treatment. OBJECTIVE: This study systematically reviews the mechanisms of propolis and honey against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and current evidence for the use of propolis and honey in COVID-19 prevention and treatment. SEARCH STRATEGY: A systematic search was conducted of electronic databases including PubMed, Scopus, ScienceDirect, and Cochrane Library from their inceptions to April 2021. INCLUSION CRITERIA: Studies that evaluated the effect of propolis or bee products against SARS-CoV-2 using in silico methods, clinical studies, case reports and case series were included. DATA EXTRACTION AND ANALYSIS: A standardized data extraction form was used, and data were extracted by two independent reviewers. Narrative synthesis was used to summarize study results concerning the use of propolis or honey in COVID-19 prevention and treatment and their potential mechanisms of action against SARS-CoV-2. RESULTS: A total of 15 studies were included. Nine studies were in silico studies, two studies were case reports, one study was a case series, and three studies were randomized controlled trials (RCTs). In silico studies, using molecular docking methods, showed that compounds in propolis could interact with several target proteins of SARS-CoV-2, including angiotensin-converting enzyme 2, the main protease enzyme, RNA-dependent RNA polymerase, and spike protein. Propolis may have a positive effect for clinical improvement in mild and moderate-to-severe COVID-19 patients, according to case reports and case series. The included RCTs indicated that propolis or honey could probably improve clinical symptoms and decrease viral clearance time when they were used as adjuvant therapy to standard of care. CONCLUSION: In silico studies showed that compounds from propolis could interact with target proteins of SARS-CoV-2, interfering with viral entry and viral RNA replication, while clinical studies revealed that propolis and honey could probably improve clinical COVID-19 symptoms and decrease viral clearance time. However, clinical evidence is limited by the small number of studies and small sample sizes. Future clinical studies are warranted.

Potential Effects of Romanian Propolis Extracts against Pathogen Strains.

The impact of globalization on beekeeping brings new economic, scientific, ecological and social dimensions to this field The present study aimed to evaluate the chemical compositions of eight propolis extracts from Romania, and their antioxidant action and antimicrobial activity against seven species of bacteria, including pathogenic ones: Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Listeria monocytogenes and Salmonella enterica serovar Typhimurium. The phenolic compounds, flavonoids and antioxidant activity of propolis extracts were quantified; the presence of flavones and aromatic acids was determined. Quercetin and rutin were identified by HPLC analysis and characterized using molecular descriptors. All propolis samples exhibited antibacterial effects, especially against P. aeruginosa and L. monocytogenes. A two-way analysis of variance was used to evaluate correlations among the diameters of the inhibition zones, the bacteria used and propolis extracts used. Statistical analysis demonstrated that the diameter of the inhibition zone was influenced by the strain type, but no association between the propolis origin and the microbial activity was found.

Allergic contact cheilitis caused by propolis: case report.

Propolis is a lipophilic resin extracted from plants by bees. The purpose of this case report was to show the importance of this substance as cause of allergic contact cheilitis. A 21-year-old female patient complained of pruritic perioral eczema for 5 years. In the past months it also affected the neck. After diagnosing contact dermatitis, she was submitted to a patch test with a Latin American baseline series. The result was strongly positive for propolis (++) and weakly positive for perfume mix I (+). After the test, the patient revealed she had been using propolis drops, per oris, for 10 years. The worsening of the condition was due to increased dose, aiming "to improve immunity", during the coronavirus disease 2019 (COVID-19) pandemic. The contact allergy to propolis might be increasing due to the widespread use of natural products. Propolis is a sensitizer to be considered in patients with long-lasting cheilitis.

Propolis and Diet Rich in Polyphenols as Cariostatic Agents Reducing Accumulation of Dental Plaque.

Conducted studies indicate the relationship between oral health and systemic diseases. Moreover, the latest research indicated that cariogenic bacteria may severely influence the course of SARS-CoV-2 infection and increase risk of COVID-19 complications. This article aims to review various applications of propolis and pay attention to a healthy diet rich in polyphenols, which may allow the reduction of dental plaque accumulation. A literature review has been conducted from June until November 2021. It showed that propolis could be a useful agent in decreasing the accumulation of dental plaque. Moreover, a diet rich in polyphenols prevents cariogenic bacteria and reduces the accumulation of dental plaque. A reduction of a dental plaque may influence the risk of a severe course of COVID-19. Therefore, propolis and a diet rich in polyphenols may play an important role in prophylaxis of systemic diseases. Recently, it has been proven that oral infection may affect cardiovascular system, musculoskeletal system, respiratory system, nervous system, as well as may be a risk factor for diabetes mellitus. These aspects should stimulate clinicians to further research about polyphenols.

The Influence of Propolis on Dental Plaque Reduction and the Correlation between Dental Plaque and Severity of COVID-19 Complications-A Literature Review.

Current studies suggest that cariogenic bacteria in dental plaque influence the severity of COVID-19 complications since the oral cavity is a reservoir for respiratory pathogens potentially responsible for the development of hospital-acquired pneumonia. This article focuses on the association between dental plaque and COVID-19 concerning the influence of altered oral biofilm on the risk of increased severity of SARS-CoV-2 infection. Moreover, it concentrates on the usefulness of propolis, with its apitherapeutic antibacterial properties, for treating oral bacterial infections co-occurring with SARS-CoV-2 infection. A review of the literature on PubMed, Cochrane Library and Medline between 2000 and 2021 revealed 56 published articles indicating that a link between dental plaque and COVID-19 complications was probable. Furthermore, they indicated that propolis may minimize COVID-19 severity by reducing dental plaque accumulation. The possibility that improved oral health could reduce the risk of COVID-19 complications should be of interest to scientists.

Investigation of potential inhibitor properties of ethanolic propolis extracts against ACE-II receptors for COVID-19 treatment by molecular docking study.

The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE-II, is a type I integral membrane protein of 805 amino acids that contains 1 HEXXH-E zinc binding consensus sequence. ACE-II has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). In this study, the potential of some flavonoids presents in propolis to bind to ACE-II receptors was calculated with in silico. Binding constants of ten flavonoids, caffeic acid, caffeic acid phenethyl ester, chrysin, galangin, myricetin, rutin, hesperetin, pinocembrin, luteolin and quercetin were measured using the AutoDock 4.2 molecular docking program. And also, these binding constants were compared to reference ligand of MLN-4760. The results are shown that rutin has the best inhibition potentials among the studied molecules with high binding energy - 8.04 kcal/mol, and it is followed by myricetin, quercetin, caffeic acid phenethyl ester and hesperetin. However, the reference molecule has binding energy of - 7.24 kcal/mol. In conclusion, the high potential of flavonoids in ethanolic propolis extracts to bind to ACE-II receptors indicates that this natural bee product has high potential for COVID-19 treatment, but this needs to be supported by experimental studies.