Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies
Abstract
:1. Introduction
2. SARS-CoV-2 and Associated Immune Response
3. Current Gaps in the Treatment of COVID-19
4. Propolis Composition and Biological Activities
5. Bee Honey Composition and Biological Activities
6. Possible Anti-COVID-19 Effects of Flavonoids in Propolis and Bee Honey Reported by Molecular Docking Studies
6.1. Flavonoids in Propolis May Inhibit the Proteolytic Processing of S Protein by Host Proteases
6.2. Flavonoids in Propolis May Inhibit the Binding of SARS-CoV-2 to Host Cell Receptors
6.3. Flavonoids in Propolis May Interrupt Viral-Host Protein Interactions That Induce an Inflammatory Response
6.4. Flavonoids in Propolis and Honey May Interrupt SARS-CoV-2 Life Cycle
7. Evidence from Experimental Studies Evaluating the Effect of Bee Products on SARS-CoV-2
8. Evidence from Human Trials Evaluating the Effect of Bee Products on Patients with COVID-19
9. Discussion
10. Conclusion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
13b | Tert-butyl(1-((S)-1-(((S)-4-(benzylamino)-3:4-dioxo-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)-amino)-3-cyclopropyl-1-oxopropan-2-yl)-2-oxo-1,2-dihydro-pyridin-3-yl) carbamate |
COVID-19 | Coronavirus Disease 2019 |
SARS-CoV-2 | Severe acute respiratory syndrome-coronavirus-2 |
ARDS | Severe acute pneumonia-associated respiratory syndrome |
M protein | Membrane protein |
E protein | Envelope protein |
S protein | Spike protein |
N protein | Nucleocapsid protein |
NSPs | Non-structural proteins |
TM | Transmembrane |
MW | Molecular weight |
IL | Interleukin |
RBD | Receptor-binding domain |
ACE-II | Angiotensin-converting enzyme-related carboxypeptidase |
TMPRSS2 | Transmembrane protease serine 2 |
PLpro | Papain-like protease |
RdRp | RNA-dependent RNA polymerase |
3CLpro | Chymotrypsin-like protease |
Mpro | Main protease |
SLiMs | Short linear motifs |
PP2A | Protein phosphatase 2A |
Tregs | Regulatory T cells |
BGP | Brazilian green propolis |
CAPE | Caffeic acid phenethyl ester |
RCSBPDB | Research Collaboratory for Structural Bioinformatics Protein Data Bank |
MLN-4760 | (S,S)-2-[1-Carboxy-2-[3-(3,5-Dichloro-Benzyl)-3h-Imidazole-4-Yl]-Ethylamino]xx-4-Methyl-Pentanoic Acid |
DUB | Deubiquitinating |
MOI | Multiplicity of infection |
TPC2 | Two-pore channel 2 |
HNS | Honey plus Nigella sativa |
LOS | Length of hospital stay |
RCTs | Randomized controlled clinical trials |
HR | Hazard ratio |
OR | Odds ratio |
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Bee-Related Compounds | SARS-CoV-2 Proteins | Possible Anti-COVID-19 Effects | References |
---|---|---|---|
CAPE | TMPRSS2 | Inhibiting S protein cleavage | [5] |
Rutin, luteolin, and CAPE | ACE-II | Inhibiting viral binding to host cell receptor | [48,51,79] |
Naringin, rutin, and quercetin | S protein | Inhibiting viral fusion in host cell membrane | [51,78] |
Rutin, nicotiflorin, luteolin, and CAPE | 3CLpro/Mpro, PLpro, and RdRp | Inhibiting viral replication and inflammatory reaction | [25,34,47,51,80,81] |
Artepillin C | PP2A-B56 | Inhibiting viral-host interactions that induce inflammation | [2] |
Bee Products | Sample and Design | Treatment | Study Outcomes | Results | References |
---|---|---|---|---|---|
Natural honey plus Nigella sativa, Anthemis hyaline (TaibUVID). | Confirmed COVID-19 patients (n = 20), contacts of COVID-19 patients (n = 20). Retrospective study. | TaibUVID orally and herbal solution inhalation. | Symptom recovery, blood count profile, and development of SARS-CoV-2 infection. | Improvement of the lymphocyte profile and earlier symptom recovery in regular users of TaibUVID. Lower incidence of SARS-CoV-2 infection in contacts. | [92] |
BGP (EPP-AF). | Confirmed COVID-19 patient aged 52 years (n = 1). Case report. | EPP-AF® 45 drops/3 times/day/2 weeks. | Early symptom recovery and viral clearance within 12 days of treatment. | Patient’s condition improved considerably. Negative nasopharyngeal swab (PCR). | [94] |
BGP (EPP-AF). | Hospitalized adult COVID-19 patients (n = 82). An open-label, single center RCT. | EG1: propolis 400 mg (n = 40). EG1: propolis 800 mg (n = 42). EG1: standard care alone (n = 42). | LOS, dependence on oxygen therapy, development of acute kidney injury, ICU admission, use of vasoactive drugs. | Decreased LOS in EG1 and EG2 to 7 and 6 days compared with 12 days in CG. No effect of propolis on oxygen dependency. Decreased renal injury in EGs compared with CG (2 vs. 10 patients). No adverse effects of propolis were depicted. | [95] |
Natural honey plus Nigella sativa (HNS). | Adults (n = 313) with moderate (n = 210) and severe (n = 103) COVID-19. A multicenter, placebo-controlled RCT. | EG: HNS (n = 107 moderate + 50 severe patients). CG: empty capsules placebo (n = 103 moderate + 53 severe patients). | Symptom recovery, viral clearance, a 30-day mortality, resumption of normal activity, oxygen saturation, and percentage of discharge from the hospital. | A 59% reduction in the time of symptom recovery in EG. Earlier virus clearance in EG. Decreased mortality by 4-folds in EG compared with CG. Higher resumption of normal activity on day 6 in moderate patients in EG than in CG. Achieving a mean oxygen saturation above 90% six days earlier in severe patients in EG. Higher hospital discharge of severe patients in EG. No adverse effects of HNS were depicted. | [96] |
Iranian green propolis extract | Confirmed COVID-19 patients aged 18–75 years (n = 80). Double-blind, placebo-controlled, RCT | EG: propolis (n = 40). CG: placebo (n = 40). | COVID-19 severity and duration over 2 weeks. | NR | [97] |
Natural honey | Non-severe COVID-19 patients aged 5–75 years (n = 1000). Single blind multicenter RCT. | EG: honey (n = 500). CG: standard care (n = 500). | Symptom recovery and viral clearance at day 14, lung recovery at day 30, mortality and viral clearance within 30 days. | NR | [68] |
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Ali, A.M.; Kunugi, H. Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies. Molecules 2021, 26, 1232. https://doi.org/10.3390/molecules26051232
Ali AM, Kunugi H. Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies. Molecules. 2021; 26(5):1232. https://doi.org/10.3390/molecules26051232
Chicago/Turabian StyleAli, Amira Mohammed, and Hiroshi Kunugi. 2021. "Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies" Molecules 26, no. 5: 1232. https://doi.org/10.3390/molecules26051232