Uncovering the Therapeutic Potential of Propolis Extract in Managing Hyperinflammation and Long COVID‐19: A Comprehensive Bioinformatics Study
et al., Chemistry & Biodiversity, doi:10.1002/cbdv.202401947, Nov 2024
In silico study showing that propolis extract may be beneficial for COVID-19. Authors used network pharmacology and bioinformatics to identify 25 inflammation-associated targets relevant to COVID-19, including STAT1, NOS2, and BTK, through integration of SARS-CoV-2 differentially expressed genes and target predictions. Molecular docking and dynamics highlighted five flavonoids with strong binding affinity to key targets. Enrichment analyses associated propolis activity with pathways implicated in viral infection and inflammation. Findings suggest propolis extract could mitigate hyperinflammation and reduce Epstein-Barr Virus reactivation.
12 preclinical studies support the efficacy of propolis for COVID-19:
In silico studies predict inhibition of SARS-CoV-2 with propolis or metabolites via binding to the spikeA,1,2 , MproB,2, RNA-dependent RNA polymeraseC,1,2 , PLproD,1, ACE2E,6, and TMPRSS2F,6 proteins.
In vitro studies demonstrate inhibition of the ACE2E,6 and TMPRSS2F,6 proteins.
Propolis may inhibit spike protein and ACE2 interaction8, may inhibit SARS-CoV-2 through interactions with MAPK15, inhibited SARS-CoV-2 in Vero E6 cells at a concentration comparable to a combination of four antiviral components9, may mitigate hyperinflammation via STAT1, NOS2, and BTK targeting3, may inhibit SARS-CoV-2 entry by interfering with ACE2/TMPRSS2 interaction7, components of propolis show ACE2 downregulation in human cells6, modulates inflammatory responses by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α7, and may suppress Epstein-Barr Virus reactivation3.
1.
Ferreira Júnior et al., An In Silico Investigation of Brazilian Green Propolis Extracts as Potential Treatment for COVID-19, ACS Omega, doi:10.1021/acsomega.5c02121.
2.
Al balawi et al., Assessing multi-target antiviral and antioxidant activities of natural compounds against SARS-CoV-2: an integrated in vitro and in silico study, Bioresources and Bioprocessing, doi:10.1186/s40643-024-00822-z.
3.
Anshori et al., Uncovering the Therapeutic Potential of Propolis Extract in Managing Hyperinflammation and Long COVID‐19: A Comprehensive Bioinformatics Study, Chemistry & Biodiversity, doi:10.1002/cbdv.202401947.
4.
Ay et al., Investigation of The Inhibition of SARS-CoV-2 Spike RBD and ACE-2 Interaction by Phenolics of Propolis Extracts, Journal of Apitherapy and Nature, doi:10.35206/jan.1471090.
5.
Siregar et al., Exploring Therapeutic Potential of Nutraceutical Compounds from Propolis on MAPK1 Protein Using Bioinformatics Approaches as Anti-Coronavirus Disease 2019 (COVID-19), BIO Web of Conferences, doi:10.1051/bioconf/20248800007.
6.
Kumar et al., Computational and experimental evidence of the anti‐COVID‐19 potential of honeybee propolis ingredients, caffeic acid phenethyl ester and artepillin c, Phytotherapy Research, doi:10.1002/ptr.7717.
7.
Ferreira et al., Antiviral and anti-inflammatory efficacy of nanoencapsulated brazilian green propolis against SARS-CoV-2, Scientific Reports, doi:10.1038/s41598-025-05683-w.
a.
The trimeric spike (S) protein is a glycoprotein that mediates viral entry by binding to the host ACE2 receptor, is critical for SARS-CoV-2's ability to infect host cells, and is a target of neutralizing antibodies. Inhibition of the spike protein prevents viral attachment, halting infection at the earliest stage.
b.
The main protease or Mpro, also known as 3CLpro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting Mpro disrupts the SARS-CoV-2 lifecycle within the host cell, preventing the creation of new copies.
c.
RNA-dependent RNA polymerase (RdRp), also called nsp12, is the core enzyme of the viral replicase-transcriptase complex that copies the positive-sense viral RNA genome into negative-sense templates for progeny RNA synthesis. Inhibiting RdRp blocks viral genome replication and transcription.
d.
The papain-like protease (PLpro) has multiple functions including cleaving viral polyproteins and suppressing the host immune response by deubiquitination and deISGylation of host proteins. Inhibiting PLpro may block viral replication and help restore normal immune responses.
e.
The angiotensin converting enzyme 2 (ACE2) protein is a host cell transmembrane protein that serves as the cellular receptor for the SARS-CoV-2 spike protein. ACE2 is expressed on many cell types, including epithelial cells in the lungs, and allows the virus to enter and infect host cells. Inhibition may affect ACE2's physiological function in blood pressure control.
f.
Transmembrane protease serine 2 (TMPRSS2) is a host cell protease that primes the spike protein, facilitating cellular entry. TMPRSS2 activity helps enable cleavage of the spike protein required for membrane fusion and virus entry. Inhibition may especially protect respiratory epithelial cells, buy may have physiological effects.
Anshori et al., 22 Nov 2024, peer-reviewed, 9 authors.
In silico studies are an important part of preclinical research, however results may be very different in vivo.
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"abstract": "<jats:p>Hyperinflammation is significant factor in long COVID, impacting over 65 million post‐COVID‐19 individuals globally. Herbal remedies, including propolis, show promise in reducing severity and pro‐inflammatory cytokines. However, the natural pharmacological role of propolis in COVID‐19 management remains underexplored. Employing network pharmacology and in silico techniques, we assessed propolis extract's potential in countering SARS‐CoV‐2‐induced inflammation. We identified 80 flavonoids via LC‐MS/MS QTOF and employed 11 anti‐inflammatory drugs as references for inflammation target fishing. Utilizing in silico techniques encompassing target fishing, molecular docking, and dynamics, we examined propolis' effects. We identified 1105 gene targets connected to inflammation through multiple validated target predictors. By integrating SARS‐CoV‐2 DEGs from GSE147507 with these targets, we Identify precisely 25 inflammation‐COVID‐19‐associated propolis targets, including STAT1, NOS2, CFB, EIF2K2, NPY5R, and BTK. Enrichment analyses highlighted primary pharmacological pathways related to Epstein‐Barr virus infection and COVID‐19. Molecular docking validated Isokaempferide, Iristectorigenin B, 3’‐Methoxypuerarin, Cosmosin, and Baicalein‐7‐O‐β‐D glucopyranoside, which exhibited strong binding affinity and stability with relevant genes. Moreover, our findings indicate that propolis ligands could potentially suppress reactivation of Epstein‐Barr Virus infections in post‐COVID‐19 cases. These findings highlight propolis as potential supplement to alleviate inflammation in COVID‐19 patients and those with prolonged symptoms, requiring additional clinical validation for confirmation.</jats:p>",
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