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.

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.

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.

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.

The effect of propolis plus Hyoscyamus niger L. methanolic extract on clinical symptoms in patients with acute respiratory syndrome suspected to COVID-19: A clinical trial.

The outbreak of Coronavirus disease 2019 (COVID-19) has caused a global health crisis. Nevertheless, no antiviral treatment has yet been proven effective for treating COVID-19 and symptomatic supportive cares have been the most common treatment. Therefore, the present study was designed to evaluate the effects of propolis and Hyoscyamus niger L. extract in patients with COVID-19. This randomized clinical trial was conducted on 50 cases referred to Akhavan and Sepehri Clinics, Kashan university of medical sciences, Iran. Subjects were divided into two groups (intervention and placebo). This syrup (containing 1.6 mg of methanolic extract along with 450 mg of propolis per 10 mL) was administered three times a day to each patient for 6 days. The clinical symptoms of COVID-19 such as: dry cough, shortness of breath, sore throat, chest pain, fever, dizziness, headache, abdominal pain, and diarrhea were reduced with propolis plus Hyoscyamus niger L. extract than the placebo group. However, the administration of syrup was not effective in the control of nausea and vomiting. In conclusion, syrup containing propolis and Hyoscyamus niger L. extract had beneficial effects in ameliorating the signs and symptoms of COVID-19 disease, in comparison with placebo groups.

Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment.

OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.

Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes challenging immune and inflammatory phenomena. Though various therapeutic possibilities have been tested against coronavirus disease 2019 (COVID-19), the most adequate treatment has not yet been established. Propolis is a natural product with considerable evidence of immunoregulatory and anti-inflammatory activities, and experimental data point to potential against viral targets. We hypothesized that propolis can reduce the negative effects of COVID-19. METHODS: In a randomized, controlled, open-label, single-center trial, hospitalized adult COVID-19 patients were treated with a standardized green propolis extract (EPP-AF®ï¸) as an adjunct therapy. Patients were allocated to receive standard care plus an oral dose of 400 mg or 800 mg/day of green propolis for seven days, or standard care alone. Standard care included all necessary interventions, as determined by the attending physician. The primary end point was the time to clinical improvement, defined as the length of hospital stay or oxygen therapy dependency duration. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Patients were followed for 28 days after admission. RESULTS: We enrolled 124 patients; 40 were assigned to EPP-AF®ï¸ 400 mg/day, 42 to EPP-AF®ï¸ 800 mg/day, and 42 to the control group. The length of hospital stay post-intervention was shorter in both propolis groups than in the control group; lower dose, median 7 days versus 12 days (95% confidence interval [CI] -6.23 to -0.07; p = 0.049) and higher dose, median 6 days versus 12 days (95% CI -7.00 to -1.09; p = 0.009). Propolis did not significantly affect the need for oxygen supplementation. In the high dose propolis group, there was a lower rate of acute kidney injury than in the controls (4.8 vs 23.8%), (odds ratio [OR] 0.18; 95% CI 0.03-0.84; p = 0.048). No patient had propolis treatment discontinued due to adverse events. CONCLUSIONS: Addition of propolis to the standard care procedures resulted in clinical benefits for the hospitalized COVID-19 patients, especially evidenced by a reduction in the length of hospital stay. Consequently, we conclude that propolis can reduce the impact of COVID-19.

Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies.

Despite the virulence and high fatality of coronavirus disease 2019 (COVID-19), no specific antiviral treatment exists until the current moment. Natural agents with immune-promoting potentials such as bee products are being explored as possible treatments. Bee honey and propolis are rich in bioactive compounds that express strong antimicrobial, bactericidal, antiviral, anti-inflammatory, immunomodulatory, and antioxidant activities. This review examined the literature for the anti-COVID-19 effects of bee honey and propolis, with the aim of optimizing the use of these handy products as prophylactic or adjuvant treatments for people infected with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Molecular simulations show that flavonoids in propolis and honey (e.g., rutin, naringin, caffeic acid phenyl ester, luteolin, and artepillin C) may inhibit viral spike fusion in host cells, viral-host interactions that trigger the cytokine storm, and viral replication. Similar to the potent antiviral drug remdesivir, rutin, propolis ethanolic extract, and propolis liposomes inhibited non-structural proteins of SARS-CoV-2 in vitro, and these compounds along with naringin inhibited SARS-CoV-2 infection in Vero E6 cells. Propolis extracts delivered by nanocarriers exhibit better antiviral effects against SARS-CoV-2 than ethanolic extracts. In line, hospitalized COVID-19 patients receiving green Brazilian propolis or a combination of honey and Nigella sativa exhibited earlier viral clearance, symptom recovery, discharge from the hospital as well as less mortality than counterparts receiving standard care alone. Thus, the use of bee products as an adjuvant treatment for COVID-19 may produce beneficial effects. Implications for treatment outcomes and issues to be considered in future studies are discussed.

Bee products as a source of promising therapeutic and chemoprophylaxis strategies against COVID-19 (SARS-CoV-2).

The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19.

The effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: This study aims to assess the effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19). TRIAL DESIGN: This is a Double-Blind, Placebo-Controlled, Parallel Arm, Randomized Phase ΙΙ Clinical Trial. PARTICIPANTS: Patients with the confirmed COVID-19 based on the PCR test are eligible to participate in the trial if they are 18 to 75 years of age and have no history of the current use of warfarin or propolis supplement and presence of sensitivity to bee products. Patients will be recruited from the Al-Zahra hospital in Isfahan city, Isfahan, Iran. INTERVENTION AND COMPARATOR: Participants (N=40) in the intervention group will receive an identical propolis tablet (containing 300 mg Iranian green propolis extract) three times a day for a period of 2 weeks. Participants (N=40) in the control group will receive an identical placebo tablet (containing 300 mg microcrystalline cellulose) three times a day for 2 weeks. All tablets are prepared by the Reyhan Naghsh Jahan Pharmaceutical Co., Isfahan, Iran. MAIN OUTCOMES: The main outcomes are changes in the coronavirus disease's clinical symptoms including duration and severity from baseline to the end of 2 weeks. RANDOMIZATION: Eligible patients will be randomly allocated in a 1:1 ratio to the intervention or control group. Randomization will be performed on the basis of permuted block sizes of 4 and will be stratified according to sex categories. Randomization sequences will be prepared by the trial's pharmacist with the use of random-number tables. BLINDING (MASKING): The trial-group assignment will be concealed from all participants, clinicians, and investigators throughout the trial. To ensure blinding, randomization sequences will be kept in identical, opaque, sealed, sequentially numbered envelopes. Only the trial's pharmacist has access to the randomization list. Also, the placebo tablet will be similar to the propolis tablet in terms of texture, taste, color, odor, and weight. Both tablets will be provided in containers that are completely identical in weight, shape, labelling, and packaging. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The calculated total sample size is 80 patients, with 40 patients in each group. TRIAL STATUS: The protocol is Version 1.0, October 10, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by March 21, 2021. TRIAL REGISTRATION: The name of the trial register: The effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A randomized, double-blind, placebo-controlled clinical trial. IRCT registration number: IRCT20200802048267N1 . Date of trial registration: 20 October 2020, retrospectively registered. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Back to the basics: Propolis and COVID-19.

The epidemiological burden of COVID-19 is a healthcare challenge throughout the world, not only in terms of testing the limits of medical capacities, but also as an enigma considering preventive strategies and methods. The upper respiratory tract mucosa is the first line of defense, as a physical barrier, as well as through multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses. 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 and help in flattening the curve. We review the effects of propolis, an old remedy with proven antiviral properties, as a possible low-cost inhibitor of SARS-CoV-2 in the oropharyngeal niche, prophylaxis, or adjuvant therapy.