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The Coronavirus Disease 2019 (COVID-19) pandemic has been going on since November 2019 in the World with different variants of SARS-CoV-2. Effective vaccine and drug investigations for COVID-19 are still ongoing. For decreasing the mortality rate of COVID-19 keeping social distance, using a mask, washing hands, and improving immune systems are important. Propolis is a natural bee product that contains various bioactive substrates such as polyphenolic acids, flavonoids, vitamins, minerals. Propolis via antiviral, anti-inflammatory, antioxidant, and antithrombotic activities could be used as prophylactic or adjuvant COVID-19 treatment.
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
Review Article/Derleme Makalesi
Apiterapi ve Doğa Dergisi
Journal of Apitherapy and Nature
The Importance of Propolis in Combating COVID-19
COVID-19 ile Mücadelede Propolisin Önemi
Meltem UÇAR1*
1Medical Laboratory Technique, Vocational School of Health Services, European University of Lefke, Lefke,
Northern Cyprus, TR-10 Mersin, Turkey
*, ORCID: 0000-0001-5554-2622
Received/Geliş Tarihi: 03/05/2021
Accepted/ Kabul Tarihi: 24/06/2021 doi: 10.35206/jan.932050
*Corresponding author / Yazışılan yazar e-ISSN: 2667-4734
The Coronavirus Disease 2019 (COVID-19)
pandemic has been going on since November
2019 in the World with different variants of
SARS-CoV-2. Effective vaccine and drug
investigations for COVID-19 are still ongoing.
For decreasing the mortality rate of COVID-
19 keeping social distance, using a mask,
washing hands, and improving immune
systems are important. Propolis is a natural
bee product that contains various bioactive
substrates such as polyphenolic acids,
flavonoids, vitamins, minerals. Propolis via
antiviral, anti-inflammatory, antioxidant, and
antithrombotic activities could be used as
prophylactic or adjuvant COVID-19
Keywords: COVID-19, SARS-CoV-2,
Abbreviations: COVID-19, Coronavirus disease 2019, WHO, World Health Organization, SARS-CoV, Severe
Acute Respiratory Syndrome Coronavirus-2, CoV, Coronaviruses, ACE-2, Angiotensin-Converting Enzyme 2,
TMPRSS2, Transmembrane Serine Protease 2, PAK 1, RAC/CDC42-activated kinase 1, IL, Interleukin, TNF-
α, Tumor necrosis factor-alpha, IFNγ, Interferon-gamma, G-CSF, Granulocyte colony-stimulating factor RdRp,
RNA-dependent RNA polymerase, PL-pro, Papain like protease, M-pro, Coronavirus main proteinase, CAPE,
Caffeic acid phenethyl ester, HIV, Human Immunodeficiency Virus, NF-κB, Nuclear factor kappa-light-chain-
enhancer, 3CL-pro, 3C-like proteinase, COX, Cyclooxygenase, iNOS, inducible nitric oxide synthase, NO,
Nitric oxide, PAI-1, Plasminogen activator inhibitor-1, BGP, Brazillian Green Propolis, EPP-AF®, The
Standardized Propolis Extract
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
As of April 26th, 2021, the world is still laboring to overcome coronavirus disease 2019
(COVID-19) in 223 countries, over 146 841 882 cases, and 3 104 743 deaths have been reported
by World Health Organization (WHO) (WHO, 2021a). COVID-19 is caused by Severe Acute
Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) which was firstly identified in Wuhan,
China, in December 2019. COVID-19 may have various symptoms, such as fever, headache,
exhaustion, sputum, hypogeusia, painful throat, dyspnea, cough, diarrhea, anorexia, dizziness,
rhinorrhea, nasal congestion, hyposmia, myalgia (Kim et al., 2020; Singhal, 2020; Vipul et al.,
2020). Most infected people will develop mild to moderate illness and recover without
hospitalization. While most common symptoms are fever, dry cough, and tiredness, serious
symptoms are difficulty breathing or shortness of breath, chest pain or pressure, loss of speech
or movement. Otherwise, some patients haven’t any symptoms too during the illness. When
someone is contaminated or infected with the SARS-CoV-2 it can take 5-6 days or take up to
14 days for getting symptoms (WHO, 2021b). Polymerase Chain Reaction (PCR), Real Time-
Polymerase Chain Reaction (RT-PCR), Complete Blood Count and other laboratory tests, X-
ray, and CT scans are used to diagnose COVID-19. CT imaging is more sensitive and specific
for diagnosing COVID-19. WHO is suggested using all symptoms, RT-PCR and other
laboratory tests, and CT imaging for diagnosing infection and emphasis that only PCR test is
not enough for diagnosis COVID-19 (Feng et al., 2020; Singhal, 2020; Zitek, 2020). Infection
is transmitted human to human among asymptomatic and symptomatic patients by coughing,
sneezing, or touching contaminated surfaces (Singhal, 2020). People who are 65 or >65 years
old or who have a chronic disease such as diabetes mellitus, chronic liver disease, chronic lung
disease, chronic renal failure, chronic cardiovascular disease, hematological malignancy, and
receiving chemotherapy or immunosuppressive agents are in the high-risk groups for COVID-
19 (Kim et al., 2020). Rapid detection, treatment, and prevention of COVID-19 are very
important for saving lives in the world urgently. Social distancing, lockdown of cities, hygienic
products have been used to control the COVID-19 Pandemic (Lima et al., 2020). Scientists are
still developing more effective vaccines and drugs for COVID-19 (Al Naggar et al., 2021).
Medical plants, some compounds that are isolated from plants, and bee products such as
propolis, honey which have antiviral activity are used by people for preventing COVID-19 and
supporting immune systems and treatment (Berretta et al., 2020; Ripari et al., 2021). This
review summarizes the information on COVID-19 disease, the anti-viral activity of propolis,
and its effects on SARS-CoV-2.
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
Coronaviruses (CoV) are a group of positive-sense single-stranded RNA viruses. SARS-CoV-
2 uses spike glycoproteins for attaching Angiotensin-Converting Enzyme 2 (ACE 2) and
Transmembrane Serine Protease 2 (TMPRSS2) of the host cell than resulting membrane fusing
(Dalan et al., 2021; Elmahallawy et al., 2021; Harisna et al., 2021). Figure 1 shows the structure
of SARS-CoV-2 (Elmahallawy et al., 2021). SARS-CoV-2 includes 4 structural proteins
(Spike, Envelope, Membrane, and Nucleocapsid proteins), Cysteine proteinase, RNA
polymerase, and nonstructural proteins (Elmahallawy et al., 2021; Sahlan et al., 2021).
ACE-2 is a receptor not only for Angiotensin II but also SARS-CoV-2 too. ACE-2 is
expressed in the ciliated airway epithelium of the lungs, enterocytes of the small intestine,
arterial and venous endothelial cells, arterial smooth muscle cells in the heart, kidneys, adrenal
glands, pancreas, skeletal muscle, and adipose tissues (Dalan et al., 2020). Because of the wide
expression of ACE-2, using inhibitors of TMPRSS2 is more useful for preventing enter of
SARS-CoV-2 into the host cell (Hoffmann et al., 2020).
Figure 1. Structure of SARS-CoV-2.
Due to the imbalance of ACE-2 pathways patients with hypertension, type II diabetes,
or cardiovascular disease belong to high-risk groups for respiratory failure and morality in
COVID-19. As there is not enough evidence that shows the harmful or beneficial effects of
using ACE-inhibitors or Angiotensin 2 Tip 1 receptor blockers for preventing COVID-19 in
Lipid Bilayer Membrane
Spike Glycoprotein
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
high-risk group patients, all patients should continue to take their medicine as before (Dalan et
al., 2020). Figure 2 shows host cell and SARS-CoV-2 (Coronavirus (SARS-CoV-2) Viral
Proteins, Sigma-Aldrich, 2021). Besides ACE-2 and TMPRSS2, RAC/CDC42-activated kinase
1 (PAK 1) is also a target for the scientist to prevent COVID-19. After SARS-CoV-2 enters the
host cell PAK 1 upregulation has occurred which causes lung inflammation, lung fibrosis, and
other mortality factors (Dalan et al. 2020). Activation of PAK 1 that also known as pathogenic
kinase is related to various diseases/disorders such as cancers, malaria, inflammation, and viral
infection including Human Immunodeficiency Virus (HIV), influenza, and COVID-19 (Maruta
& He, 2020). Increased PAK 1 in a host cell induces replication of SARS-CoV-2 and inhibits
immune response too (Dalan et al., 2020). The other problem in COVID-19 patients is cytokine
storm that occurred after increased production of proinflammatory cytokines such as
Interleukins (IL) (IL2, IL-6, IL7, IL-10), Tumor necrosis factor-alpha (TNFα), Interferon-
gamma (IFNγ), Granulocyte colony-stimulating factor (G-CSF). Cytokine storms may cause
multi-organ system failure that is a life-threatening disorder (Elmahallawy et al., 2021). The
other mechanism for fighting against SARS-CoV-2 is suppressing its replication by different
agents. RNA-dependent RNA polymerase (RdRp) that catalyzes the synthesis of coronavirus
RNA, is so important for coronaviral replication/transcription machinery complex. Also, Papain
like protease (PL-pro) and coronavirus main proteinase (M-pro) that has a role to replicate and
generate new RNA are therapeutic targets for developing pharmacy too (Huang et al., 2020).
Figure 2. Host cell and SARS-CoV-2
Lipid Membrane
Host Cell
Spike Protein
Membrane Protein
Envelope Protein
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
Several drugs were investigated to treatment COVID-19 such as nevilnafir, as a RdRp
inhibitor remdesivir, ribavirin, favipiravir, as a protease and proteinase inhibitor lopinavir and
darunavir, as a PAK 1 blocker melatonin, ciclesonide, ivermection, ketorolac, chloroquine, and
hydrochloroquine and propolis (Harisna et al., 2021; Huang et al., 2020; Maruta & He, 2020).
Also, several reports suggest that chloroquine and hydrochloquine caused serious arrhythmia,
kidney injuries, liver problems, blood and lymph system disorders, and failure in patients with
COVID-19 (United States Food and Drug Administration, 2020).
Some SARS-CoV-2 mutations repressive vaccine developments, affect the affinity to
ACE-2 receptor and infectiousness. and immune response (Conti et al., 2021; Huang et al.,
2020; Volz et al., 2021; Zhang et al., 2020). Different mutants form of SARS-CoV-2 found in
the United Kingdom, Brazil, and Sound Africa and recently double mutant SARS-CoV-2 found
in India. Scientists need time to be sure this variant is more deadly or more transmissible
( On the other hand, various
supplements, herbal and apitherapy products such as ginseng extracts, garlic extracts,
echinacea, curcumin extracts, propolis, honey, royal jelly, bee wax, bee venom, bee pollen,
quercetin, Vitamin C, Vitamin D, Vitamin E, zinc, selenium used to support treatment of
COVID-19 by antiviral, anti-inflammatory, antioxidant and immunomodulatory activities (Ali
& Kunugi, 2021; Al Naggar et al., 2021; Jin et al., 2020; Keflie et al., 2021).
Propolis is a bee product that occurred by molding resinous balsam of plants and trees with bee
wax and saliva. Propolis is also known as bee glue originates from Greek and occurred Pro- (in
meaning for or defense) and -polis (in meaning city) word parts that are a defense of city or
hive. Bees use propolis as a detoxification agent and fixing material for their hives to maintain
homeostasis, to promote a beneficial microbiome, and protect from insects and animals
(Burdock, 1998; Zulhendri et al., 2021). Propolis is also used by Egyptians, Greeks, Romans,
and Incas for wound healing, corpse embalming, and antipyretic. It was used in Europe in the
17th and 20th centuries as an antibacterial agent and during the Second World War due to the
antimicrobial and anti-inflammatory activity (Santos et al., 2019). Propolis compositions and
colors can change depending on the geographic area, climate. Generally, propolis colors are
dark brown, dark green, and dark yellow. Some propolis samples were shown in Figure 3
(Çolak, 2009).
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
Propolis consists of 50% resins, 30% bee wax, 10% aromatic and essential oils, 5% bee
pollen, 5% multiple organic compounds, vitamins, and minerals (Ali & Kunugi, 2021). It
includes more than 300 different compounds such as flavonoids, phenolic acids, phenolic acid
esters, terpenoids, xanthones, fatty acids, volatile fatty acids, ketones, lactones, steroids,
pollens, various minerals, vitamins. Some phenolic compounds and flavonoids found in
propolis are shown in Table 1 (Çolak, 2009; Duca et al., 2019; Santos et al., 2019;).
Figure 3. Propolis samples
Propolis can solve with ethanol, methanol, diethyl ether, acetone, toluene,
trichloroethylene, oils, water, and others with different ratios and compositions (Burdock, 1998;
Ripari et al., 2021). Commercial many kinds of extracts with different concentrations may find
in markets and pharmacies in capsule, liquid, pastilles or supplement form alone or with the
other herbals, vitamins or minerals. As for its antibacterial and antimicrobial activities, it is used
for the production of toothpaste and mouthwash solutions. (Burdock, 1998; Santoset al., 2019;
Zulhendri et al., 2021). Propolis is also used by the food industry and cosmetic industry
especially its antibacterial, antioxidant, and antiaging properties, and recently it is famous and
important in veterinary medicine too (Santos et al. 2019).
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
Table 1. Some flavonoids and phenolic compounds found in propolis
Propolis has various biological activities for humans such as antioxidant, anti-
inflammatory, antibacterial, antifungal, antiviral, antimutagenic, antitumoral, anticancer,
cytotoxic, anti-proliferative, anti-angiogenic, immunomodulatory (Braakhuis, 2019; Burdock,
1998; Zulhendri et al., 2021). Figure 4 summarise the use of propolis with its properties for
bees and humans (Zulhendri et al., 2021).
Figure 4. The use of propolis by bees and humans
Phenolic Compounds
3-(4-hydroxy-3-(oxo-butenyl)-phenylacrylic acid
3,5-diphenyl-4-hydroxycinnamic acid derivate
p-Coumaric acid
Artepillin C
Caffeic acid
Caffeic acid phenethyl ester (CAPE)
Feruric acid
Mono/Dicaffeoylquinic acids
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
As mentioned before propolis and propolis-derived compounds such as CAPE, benzoic acid,
resveratrol, p-cumaric acid, quercetin, chrysin, pinocembrin, and galangin have antiviral, anti-
inflammatory, antioxidant, and antithrombotic activity. In previous studies, it was shown that
propolis and its extracts have antiviral activity against both DNA and RNA virus such as Herpes
Simplex Virus Type 1 and Type 2, Adenovirus Type 2, Vesicular Stomatitis Virus, Poliovirus
Type 2, Varicella zoster virus, HIV, Influenza. (Burdock, 1998; Governa et al., 2019; Haris et
al., 1997; Labska et al., 2018; Yildirim et al., 2016). It was reported that various propolis
fractions affected the replication of Vaccinia Virus, Newcastle Disease Virus, and Influenza
Viruses A and B (Burdock, 1998). Debiagi et al. (1990) reported that kaempferol and chrysine
were reduced the replication of several Herpes Viruses, Adenoviruses, and a Rotavirus
concentration-dependently and quercetin was reduced infectivity and intracellular replications
of viruses in high concentrations. Also, Erdemli et al. (2015) suggested that CAPE inhibits the
HIV-1 infection, nuclear factor kappa-light-chain-enhancer (NF-κB) production, and Hepatitis
C virus replication too. Singh et al. (2020) showed that hesperidin has a higher binding activity
to RdRp of SARS-CoV-2 than remdesivir, and many polyphenols such as myricetin,
epigallocatechin gallate, theaflavin, theaflavin-3’-O-gallate, theaflavin-3’-gallate, theaflavin
3,3’-digallate, quercetagetin, and myricetin strongly bind to the active site of RdRp and other
polyphenols such as quercetin, curcumin, kaempferol, epicatechin can bind to RdRp with lower
binding energy than remdesivir. It was concluded that some natural polyphenols can be used as
an inhibitor of RdRp of SARS-CoV-2.
On the other hand, Maruta & He (2020) suggested that caffeic acids, CAPE, Artepillin
C, nymphaeols inhibit PAK1 activity, act like PAK1 inhibitors, and could be useful for
inhibiting or preventing COVID-19-induced lung fibrosis and stimulating the immune system.
Also, 3C-like proteinase (3CLpro) is an important enzyme that has a role replication of the
virus. It was shown that 2’,4’-dihydroxychalcone and 2’,4’-dihyroxy-3’-methoxychalcone that
also found in propolis have potential repressing properties against 3CLpro. As amyrin
(Triterpenes), procyanidin and proanthocyanidin influence the activity of 2’-o-ribose
methyltransferase, propolis compounds have potential restrictive properties against
methyltransferase too (Elmahallawy et al., 2021). Ali & Kunugi (2021) reviewed that rutin,
nicotiflorin, luteolin, CAPE, and Artepillin C inhibit viral replication and inflammatory
reactions by affecting 3CLpro/Mpro, PLpro, RdRp, and B56 regulatory unit of phosphatase
2A. Sahlan et al. (2021) and Kumarb et al. (2020) showed that propolis components glyasperin
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
A, broussoflavonol F, and CAPE have binding affinity to SARS-CoV-2 main protease and have
therapeutic value for COVID-19.
Also, Khayrani et al. (2021) detected that propolis components glyasperin A,
broussoflavonol F, sulabiroins A, isorhamnetin, and (25)-5,7-dihydroxy-4’-methoxy-8-
prenylflavanone have the potential to inhibit the binding of ACE-2 and SARS-CoV-2. As
phenolic compounds of propolis such as galangin, p-coumaric acid, quercetin, chrysin, and
kaempferol could block or reduce the adsorption and entrance of the virus into the host cells,
propolis consumption might be useful for protecting COVID-19 and supporting adaptive
immune response (Lima et al., 2020). In previous in vitro and in vivo studies, it was shown that
flavonoids could inhibit the activity of ACE. Recently Guler et al. (2021) used ten flavonoids
(Caffeic acid, CAPE, chrysin, galangin, myricetin, rutin, hesperetin, pinocembrin, luteolin, and
quercetin) for detecting their binding ability to ACE-2 receptors and it was shown that rutin has
the best inhibition potentials for ACE-2 receptors and then followed by myricetin, CAPE,
hesperetin, and pinocembrin. It was concluded that flavonoids in ethanolic propolis extracts
have a high potential for COVID-19 treatment by inhibition of ACE-2 receptors and preventing
entry of virus to host cells (Guler et al., 2021). Also, Refaat et al. (2021) and Vijayakumar et
al. (2020) established that rutin, luteolin, and CAPE inhibit ACE 2 receptors too. Kumara et al.
(2020), showed that CAPE inhibits the TMPRSS2 and block the entry of SARS-CoV-2 into the
cell. Refaat et al. (2020) and Jain et al. (2021) detected that naringin, rutin, and quercetin have
the binding activity to S protein and inhibit viral fusion in the host cell membrane. Harisna et
al. (2021) suggested that propolis components genistin, methylophopogonone A and 3’-
methoxydaidzin inhibit main protease and spike protein and these compounds could be used as
antiviral agents.
The other mechanism of antiviral activity of propolis may be related to its zinc content.
Propolis has variable amounts of zinc such as 21 mg/kg or 9326 mg/kg (Cvek et al., 2008; Tosic
et al., 2017). Zinc ions inhibit viral enzymes that are important for the replication of the virus
in the host cells (te Velthuis et al., 2010). Kaushik et al. (2017) reported that zinc salts block
hepatitis E virus replication by inhibiting of RdRp. Also, zinc has the potential to threaten
COVID-19 by antioxidant, anti-inflammatory, and immunomodulatory properties. Zinc can
suppress the expressing of various chemokines, acute phase proteins such as fibrinogen and C-
reactive protein, proinflammatory cytokines, and some factors that have a role in inflammatory
responses such as inhibition of NFκB and modulation of T cell functions that cause cytokine
storms in COVID-19 (Keflie et al., 2021).
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
Another trace element in propolis is selenium that has a role in maintaining adaptive
immune systems, inhibiting proinflammatory cytokines, chemokines, and production of free
oxygen radicals. Experimentally it was shown that a selenium-deficient diet in mice is related
to developing lung injury in post-influenza virus infections (Keflie et al., 2021; Suhupharani et
al., 2019). Suhupharani et al. (2019) biosynthesized selenium nanoparticles from ethanolic
extracts of propolis for human health due to the antimicrobial and antioxidant activity of
Also, it was established that Vitamin A, Vitamin B12, Vitamin C, Vitamin D, Folate,
Pyridoxine, Nicotinamide, and Retinoic acid have a protective role against COVID-19 by
antioxidant, antiviral, anti-inflammatory activities and affecting the immune response (Keflie
et al., 2021). It is also known that propolis has many kinds of vitamins and micronutritions and
it could support immune systems too (Burdock, 1998; Marcucci, 1995).
Additionally, the anti-inflammatory activity of propolis is related to its components such
as phenolic acids and their esters, flavonoids, steroids, terpenoids, and amino acids. The basic
mechanisms of anti-inflammatory activity of propolis are the inhibition of cyclooxygenase
(COX) and prostaglandin biosynthesis, antioxidant activity, inhibition of nitric oxide (NO)
synthesis, reducing the level of cytokines, and immunosuppressive activity (Braakhuis, 2019).
In many studies it was reported that CAPE, quercetin, naringenin, pinocembrin, Artepillin C,
terpenoids showed anti-inflammatory activity by inhibiting COX-2, suppressing the production
of prostaglandins and leukotrienes, reducing the expression of inflammatory mediators such as
IL-10, IL-1β, inducible nitric oxide synthase (iNOS) and inhibiting the production of TNF-α,
IL-1β, IL-6, NF-κB, NO (Braakhuis, 2019; Santos et al., 2019; Zulhendri et al., 2021).
Tromboembolism, thrombosis, and microthrombosis are common in COVID-19
patients and associated with high mortality rates of COVID-19. Generally, anticoagulants use
to reduce mortality. In a previous study antithrombotic effect of propolis was also established
by decreasing platelet aggregation, other thrombosis-related parameters and suppressing
lipopolysaccharide-induced increases in plasminogen activator inhibitor-1 (PAI-1) in mice
(Berreta et al., 2020). Quercetin might use for thrombotic disease treatment as a thrombin
inhibitor. Quercetin may utilize blood clotting dysregulation conduced by viral infection
(Berreta et al., 2020; Shi et al., 2012). In an in vivo study, it was detected that CAPE inhibits
collagen-induced platelet aggregation via downregulating Tromboksane B2, COX-1, and 5-
hydroxytryptamine and increasing NO and cyclic guanosine monophosphate activity. In
addition, it was shown that CAPE, galangin, pinostropin inhibit platelet aggregation and
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
propolis components including CAPE have the potential to threaten thrombotic disease (Ohkura
et al., 2020).
Duarte Silveria et al. (2021) used nan-alcoholic preparation of Brazillian Green Propolis
(BGP) The Standardized Propolis Extract (EPP-AF®) at two concentrations (400 mg and 800
mg) for 82 hospitalized adult COVID-19 patients and evaluated the patient's length of hospital
stay, dependence on oxygen therapy, development of acute kidney injury, intensive care unit
admission and use of vasoactive drugs. 400 mg BGP EPP-AF® has 21.2 total flavonoids such
as quercetin and 54 mg of total phenolics, such as gallic acid. It was shown that BPG treatment
decreased the length of hospital stay (6 days for 400 mg BGP EPP-AF®, 7 days for 800 mg
BGP EPP-AF®, and 12 days for the control group (n=42)) and renal injury significantly, but
didn’t have any effect on the need for oxygen therapy and didn’t observe any side effect of
propolis. In a case report BGP (EPP-AF®) confirmed a COVID-19 patient who was 52 years
old in a dose of 45 drops/3 times/day for 2 weeks. Patients viral clearance occurred within 12
days of treatment (Fiorini et al., 2021) Kosari et al. (2021) used a syrup that contains 1.6 mg
Hyoscyamus niger L. extract and 450 mg propolis per 10 mL, in 25 COVID-19 patients aged
between 17-85 and 25 patients also classified as placebo group in the investigation. In this
study, 10 mL syrup was administered during the 6 days three times a day. It was shown that
syrup reduced the clinical symptoms of COVID-19 such as dry cough, shortness of breath, sore
throat, chest pain, headache, dizziness, fever, abdominal pain, and diarrhea but didn’t have any
effect on nausea and vomiting. The dose of propolis at 500 mg/day is approximately equal to
30 drops of propolis extract (11% w/v of dry matter). Berretta et al. (2020) claim that 30
drops/day or one capsule might be used for preventing purposes of propolis but Soroy et al.
(2014) suggested that 1200 mg/day water extract of propolis capsule (Propoelix™) could
decrease the level of TNF-α and length of hospitalized day and increase platelet count in 31
patients with dengue hemorrhagic fever that is caused by the mosquito-borne dengue viruses.
While production and developing SARS-CoV-2 vaccines and drugs are continued individually
people should protect themselves by having potent immunity as well as using masc, antiseptics,
keeping social distance, and washing hands against COVID-19. Natural products such as
propolis could be useful for improving immune response by immunomodulatory activity,
protecting binding, entry, and colonization of SARS-CoV-2 in the host cells of people by
antiviral activity, preventing cytokine storms and thrombosis, various tissue injuries such as
Journal of Apitherapy and Nature/Apiterapi ve Doğa Dergisi, 4(1), 22-40, 2021
lung, kidney by the antioxidant, anti-inflammatory and antithrombotic activity in COVID-19
patients. Also, it is important to increase the number of randomized and controlled clinical trials
to assess the benefits and therapeutic potential of propolis in COVID-19. But people who
haven’t any allergies to propolis might use propolis for protecting themselves against SARS-
CoV-2 and COVID-19.
Al Naggar, Y., Giesy, J.P., Abdel-Daim, M. M., Ansari, M. J., Al-Kahtani, S. N. & Yahya, G.
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... Zinc ions block viral enzymes necessary for the virus to replicate in the host cells. Selenium inhibits proinflammatory cytokines [69]. It was revealed in many studies that propolis inhibits PAK-1 and interacts with ACE2 and TMPRSS2, which may aid in reducing or preventing SARS-CoV-2 host cell invasion as given in Table 4 [74]. ...
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The most fascinating product of honeybee is propolis. It has an immense role in dentistry, dermatology, and otorhinolaryngology. The increased popularity of propolis as an important remedy is due to its constituents, which have anti-inflammatory, immunomodulatory, antihepatotoxic, anti-cancerous, antifungal, antioxidant, antidiabetic, and antiviral activities. The diverse biological and pharmacological activities of propolis have piqued the interest of many scientists. Many techniques like gas chromatography-mass spectrometry, chromatography, and spectroscopy are being used to identify different propolis constituents. Flavonoids, phenolic acids, and their esters are the most pharmacologically active molecules of propolis and are known to disrupt the replication machinery of the virus corroborating the anti-coronavirus activity of propolis. The main aim of this article is to provide an insight of the increasing theragnostic uses of propolis and its nanoparticles, including their chemical analysis, diverse biological activities, and the necessity for chemical standardization. In this review, we have focused at the promising effects of propolis, its optimization, and its liposomal formulation as a therapeutic intervention for COVID-19 and its accompanying comorbidities.
... The coronavirus (SARS-COV-2) that causes upper respiratory tract infection and it has many different symptoms. Diseases such as fever, headache, weakness, sputum, hypogeusia, sore throat, dyspnea, cough, diarrhea, anorexia, dizziness, rhinorrhea, nasal congestion, hyposmia and myalgia are examples of these symptoms [1]. There are seven different types of coronavirus known to infect humans, called the human coronavirus (CoVh). ...
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The new type of coronavirus infection (COVID-19), caused by coronavirus-2 (SARS-CoV-2), has led to a world pandemic due to severe acute respiratory syndrome. In addition to drug and vaccine studies for COVID-19, studies on various foods maintain to increase immunity and alternative treatment, and in this context, bee products are also being researched. Although many studies are showing that bee products have antimicrobial properties and immune-enhancing effects, there are limited studies on the effectiveness of these products against coronavirus. Some peptides in royal jelly are reported to be potent antibacterial and antifungal agents that may be beneficial for avoiding co-infections in COVID-19 patients. Positive results have been found Pollen, a fine and powder-like substance produced by flowering plants and collected by bees, in many studies investigating the effects of pollen on health such as antimicrobial, antiviral and anti-inflammatory. Bee venom; It is a yellowish-colored, bitter-sweet, pungent-smelling substance that is produced in the venom sac of bees, normally in liquid form, but dries up and crystallizes after contact with air. Melittin, the primary component of bee venom having more than 40 biologically and pharmacologically active compounds including phospholipase A2, histamine, epinephrine, free amino acids, peptide and apamin, has been stated to have antitumor, antimicrobial, anti-nociceptive and anti-inflammatory activities. Phospholipase A2 (PLA2) secreted from bee and snake venom is known to have strong anti-HIV activities. Melittin, phosphorylase A2 and hyaluronidan, which are the most significant components of bee venom, constitute 50% of bee venom. Moreover, researches on the relationship between bee venom and COVID-19 are limited. The target of this review is to bring together the studies on the health effects of royal jelly, bee pollen and bee venom, and to contribute to the existing studies.
The ethnopharmacological approach combined with chemical and biological methods can be a useful model in the field of pharmacology. One of these approaches, apitherapy, is the use of bee and hive products for therapeutic purposes. Propolis is among the best known of these bee products. The chemical composition of propolis varies according to the local or endemic flora, bee species, geographical origin and season. This study is to determine the antimicrobial activity differences between chestnut and polifloral origin propolis against various pathogenic bacterial species. First of all, the Liquid Chromatography-Mass Spectrometry (LC-MS/MS) method was used for the determination of bioactive components known to be responsible for antimicrobial activity. Folin-Ciocalteu method and colorimetric aluminum chloride assay were used to determine the total phenolic (TP) and flavonoid (TF) amounts. 19 different pathogenic microorganisms were selected to test the antimicrobial activity levels of propolis samples with agar well diffusion and minimum inhibitory concentration (MIC) methods. TP and TF values of chestnut propolis (71.06 mg GAE/mL-11.75 mg QE/mL) were significantly higher than polifloral sample (36.84 mg GAE/mL-7.04 mg QE/mL). Chrysin, a flavone derivative, was the most abundant compound in both samples. The MIC values of chestnut propolis ranged from 19.5 to 2500 µg/mL, while the MIC value of polifloral origin propolis was between 39.06 and 5000 µg/mL. The most susceptible strain was Mycobacterium smegmatis for both samples with different concentration. Notably, it was observed that the botanical origins affect the chemical composition of propolis, and this situation can also be effect antibacterial and antifungal activity in respective propolis because of the different amount and diversity of bioactive compounds. Consequently, chestnut propolis is a promising candidate for drug discovery that can be used to treat some infectious diseases, including resistant bacteria.
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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.
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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®️) 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®️ 400 mg/day, 42 to EPP-AF®️ 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 to 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.
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Docking analysis of propolis's natural compound was successfully performed against SARS-CoV-2 main protease (Mpro) and spike protein subunit 2 (S2). Initially, the propolis's protein was screened using chromatography analysis and successfully identified 22 compounds in the propolis. Four compounds were further investigated, i.e., neoblavaisoflavone, methylophiopogonone A, 3′-Methoxydaidzin, and genistin. The binding affinity of 3′-Methoxydaidzin was −7.7 kcal/mol, which is similar to nelfinavir (control), while the others were −7.6 kcal/mol. However, we found the key residue of Glu A:166 in the methylophiopogonone A and genistin, even though the predicted binding energy slightly higher than nelfinavir. In contrast, the predicted binding affinity of neoblavaisoflavone, methylophiopogonone A, 3′-Methoxydaidzin, and genistin against S2 were −8.1, −8.2, −8.3, and −8.3 kcal/mol, respectively, which is far below of the control (pravastatin, −7.3 kcal/mol). Instead of conventional hydrogen bonding, the π bonding influenced the binding affinity against S2. The results reveal that this is the first report about methylophiopogonone A, 3′-Methoxydaidzin, and genistin as candidates for anti-viral agents. Those compounds can then be further explored and used as a parent backbone molecule to develop a new supplementation for preventing SARS-CoV-2 infections during COVID-19 outbreaks.
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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 replica-tion. 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 Ni-gella 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.
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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 beemade 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.
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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus that infects humans and a number of animal species causing coronavirus disease-19 (COVID-19), a respiratory distress syndrome which has provoked a global pandemic and a serious health crisis in most countries across our planet. COVID-19 inflammation is mediated by IL-1, a disease that can cause symptoms such as fever, cough, lung inflammation, thrombosis, stroke, renal failure and headache, to name a few. Strategies that inhibit IL-1 are certainly helpful in COVID-19 and can represent one of the therapeutic options. However, until now, COVID-19 therapy has been scarce and, in many cases, ineffective, since there are no specific drugs other than the vaccine that can solve this serious health problem. Messenger RNA (mRNA) vaccines which are the newest approach, are already available and will certainly meet the many expectations that the population is waiting for. mRNA vaccines, coated with protected soft fatty lipids, use genetic mRNA (plus various inactive excipients) to make a piece of the coronavirus spike protein, which will instruct the immune system to produce specific antibodies. The soft fatty lipids allow the entry of mRNA into cells where it is absorbed into the cytoplasm and initiates the synthesis of the spike protein. In addition, vaccination also activates T cells that help the immune system respond to further exposure to the coronavirus. mRNA induces the synthesis of antigens of SARS-CoV-2 virus which stimulate the antibody response of the vaccinated person with the production of neutralizing antibodies. The new variant of the coronavirus-19 has been detected in the UK where, at the moment, the London government has imposed a lockdown with restrictions on international movements. The virus variant had already infected 1/4 of the total cases and in December 2020, it reached 2/3 of those infected in the UK. It has been noted that the spreading rate of the British variant could be greater than 70% of cases compared to the normal SARS-CoV-2 virus, with an R index growth of 0.4. Recent studies suggest that coronavirus-19 variation occurs at the level N501Y of the spike protein and involves 23 separate mutations on the spike, 17 of which are linked to the virus proteins, thus giving specific characteristics to the virus. In general, coronaviruses undergo many mutations that are often not decisive for their biological behavior and does not significantly alter the structure and the components of the virus. This phenomenon also occurs in SARS-CoV-2. It is highly probable that the variants recently described in the UK will not hinder vaccine-induced immunity. In fact, the variant will not break the vaccine although it may have some chance of making it a little less effective. Therefore, it is pertinent to think that the vaccine will work against the SARS-CoV-2 variant as well. In today's pandemic, the D614G mutation of the amino acid of corronavirus-19, which emerged in Europe in February 2020 is the most frequent form and causes high viral growth. The previously infrequent D614G mutation is now globally dominant. This variant, which is being tested by many international laboratories, is rapidly spreading across the countries and a series of vaccinated subjects are testing to see if their antibodies can neutralize the new variant of SARS-CoV-2. This variant has a very high viral growth and is less detectable with the RT-PCR technique in the laboratory. It has been reported that the British variant that increases viral load does not cause more severe effects in the respiratory tract and lung disease, therefore, it is certain that the variant is growing rapidly and must be kept under control; for this reason, laboratory data is expected impatiently. The study on the many variants that coronavirus-19 presents is very interesting and complete and clearer data on this topic will be ready in the near future. In addition, it is still unclear whether the different variants discovered in many countries, including Africa, share the same spike protein mutation and therefore, this is another study to elaborate on. In order to be certain and to not have unexpected surprises, we need to reduce the spread and the transmission speed of viral variants that could appear around the world, creating new pandemics. For this reason, the scientific community is on the alert since laboratory tests on serum antibodies from COVID-19 survivors have been reported to be less effective in attacking the variant. In light of the above, the scientific community must be on the alert as larger variants of the spike protein could escape vaccine-induced antibodies, which for now are of great help to the community and can save millions of lives. Deepening the study of spike protein mutations will help to better understand how to combat coronavirus-19 and its variants.
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Background Propolis is a resinous product that is collected from plants by bees to cover holes and crevices in their hives. Propolis has potent antibacterial, antiviral, anti-inflammatory, wound healing, and anticancer properties. Propolis has been used therapeutically by humans for centuries, including the treatment of dental caries and mouth infections. Highlight This review article attempts to analyze the potential use of propolis in general dentistry and oral health management. Conclusion Propolis is potentially useful in dentistry and oral health management based on available in vitro, in vivo, and ex vivo studies, as well as human clinical trials.
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Among candidate treatment options for COVID-19, propolis, produced by honey bees from bioactive plant exudates, has shown potential against viral targets and has demonstrated immunoregulatory properties. We conducted a randomized, controlled, open-label, single center trial, with a standardized propolis product (EPP-AF) on hospitalized adult COVID-19 patients. Patients received standard care plus propolis at an oral dose of 400mg/day (n=40) or 800mg/day (n=42) for seven days, or standard care alone (n=42). 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. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Time in the hospital after intervention was significantly shortened in both propolis groups compared to the controls; median 7 days with 400mg/day and 6 days with 800mg/day, versus 12 days for standard care alone. Propolis did not significantly affect the need for oxygen supplementation. With the higher dose, significantly fewer patients developed acute kidney injury than in the controls (2 versus 10 of 42 patients). Propolis as an adjunct treatment was safe and reduced hospitalization time. The registration number for this clinical trial is: NCT04480593 (20/07/2020).
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Coronavirus disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Up to date, there has been no specific cure to treat the disease. Indonesia is one of the countries that is still fighting to control virus transmission. Yet, at the same time, Indonesia has a rich biodiversity of natural medicinal products that potentially become an alternative cure. Thus, this study examined the potency of a natural medicinal product, Sulawesi propolis compounds produced by Tetragonula sapiens, inhibiting angiotensin-converting activity enzyme-2 (ACE-2), a receptor of SARS-CoV-2 in the human body. In this study, molecular docking was done to analyze the docking scores as the representation of binding affinity and the interaction profiles of propolis compounds toward ACE-2. The results illustrated that by considering the docking score and the presence of interaction with targeted sites, five compounds, namely glyasperin A, broussoflavonol F, sulabiroins A, (2S)-5,7-dihydroxy-4′-methoxy-8-prenylflavanone and isorhamnetin are potential to inhibit the binding of ACE-2 and SARS-CoV-2, with the docking score of −10.8, −9.9, −9.5, −9.3 and −9.2 kcal/mol respectively. The docking scores are considered to be more favorable compared to MLN-4760 as a potent inhibitor.