Uncovering the Therapeutic Potential of Propolis Extract in Managing Hyperinflammation and Long COVID‐19: A Comprehensive Bioinformatics Study

Anshori et al., Chemistry & Biodiversity, doi:10.1002/cbdv.202401947

Nov 2024

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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.

8 preclinical studies support the efficacy of propolis for COVID-19:

4 In Silico studies1-4

4 In Vitro studies1,3,5,6

In Silico studies predict inhibition of SARS-CoV-2 with propolis or metabolites via binding to the spikeA,1, M^proB,1, and RNA-dependent RNA polymeraseC,1 proteins. Propolis may inhibit spike protein and ACE2 interaction5, may inhibit SARS-CoV-2 through interactions with MAPK14, inhibited SARS-CoV-2 in Vero E6 cells at a concentration comparable to a combination of four antiviral components6, may mitigate hyperinflammation via STAT1, NOS2, and BTK targeting2, and may suppress Epstein-Barr Virus reactivation2.

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1. 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.springeropen.com, doi.org.

2. 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.wiley.com, doi.org.

3. 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.org.tr, doi.org.

4. 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.bio-conferences.org, doi.org.

5. dos Santos et al., Countercurrent chromatography isolation of green propolis biomarkers: potential blockers of SARS-CoV-2 RBD and ACE2 interaction, Journal of Chromatography A, doi:10.1016/j.chroma.2024.465265.sciencedirect.com, doi.org.

6. Karaoğlu et al., Chewable tablet with herbal extracts and propolis arrests Wuhan and Omicron variants of SARS-CoV-2 virus, Journal of Functional Foods, doi:10.1016/j.jff.2023.105544.sciencedirect.com, doi.org.

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 M^pro, also known as 3CL^pro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting M^pro 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.

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.

This Paper Propolis All

DOI record: { "DOI": "10.1002/cbdv.202401947", "ISSN": [ "1612-1872", "1612-1880" ], "URL": "http://dx.doi.org/10.1002/cbdv.202401947", "abstract": "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.", "alternative-id": [ "10.1002/cbdv.202401947" ], "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2024-08-13" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "2024-11-19" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 3, "value": "2024-11-22" } ], "author": [ { "affiliation": [ { "name": "Institut Teknologi Bandung School of Electrical Engineering and Informatics Jl. Ganesa No. 10 40132 Bandung INDONESIA" } ], "family": "Anshori", "given": "Isa", "sequence": "first" }, { "affiliation": [ { "name": "Institut Teknologi Bandung School of Electrical Engineering and Informatics Jalan Ganeca 10 Bandung 40132 Bandung INDONESIA" } ], "family": "Marcius", "given": "Donny", "sequence": "additional" }, { "affiliation": [ { "name": "Nano Center Indonesia Nano Center Indonesia Jalan PUSPIPTEK 15314 South Tangerang INDONESIA" } ], "family": "Syaifie", "given": "Putri Hawa", "sequence": "additional" }, { "affiliation": [ { "name": "Universitas Muhammadiyah Kalimantan Timur Faculty of Pharmacy Jl. Ir. H. Juanda No.15 75124 Samarinda INDONESIA" } ], "family": "Siregar", "given": "Khalish Arsy Al Khairy", "sequence": "additional" }, { "affiliation": [ { "name": "Nano Center Indonesia Nano Center Indonesia Jalan PUSPIPTEK South Tangerang 15314 South Tangerang INDONESIA" } ], "family": "Syakuran", "given": "Luqman Abdan", "sequence": "additional" }, { "affiliation": [ { "name": "Nano Center Indonesia Nano Center Indonesia Jalan PUSPIPTEK South Tangerang 15314 South Tangerang INDONESIA" } ], "family": "Jauhar", "given": "Muhammad Miftah", "sequence": "additional" }, { "affiliation": [ { "name": "Nano Center Indonesia Nano Center Indonesia Jalan PUSPIPTEK South Tangerang 15314 South Tangerang INDONESIA" } ], "family": "Arda", "given": "Adzani Gaisani", "sequence": "additional" }, { "affiliation": [ { "name": "Institut Teknologi Bandung School of Electrical Engineering and Informatics Jalan Ganeca 10 40132 Bandung INDONESIA" } ], "family": "Shalannanda", "given": "Wervyan", "sequence": "additional" }, { "affiliation": [ { "name": "National Research and Innovation Agency Republic of Indonesia Research Center for Vaccine and Drug Jalan Raya Bogor 16911 Cibinong INDONESIA" } ], "family": "Mardliyati", "given": "Etik", "sequence": "additional" } ], "container-title": "Chemistry & Biodiversity", "container-title-short": "Chemistry & Biodiversity", "content-domain": { "crossmark-restriction": true, "domain": [ "onlinelibrary.wiley.com" ] }, "created": { "date-parts": [ [ 2024, 11, 22 ] ], "date-time": "2024-11-22T14:04:14Z", "timestamp": 1732284254000 }, "deposited": { "date-parts": [ [ 2024, 11, 22 ] ], "date-time": "2024-11-22T14:04:16Z", "timestamp": 1732284256000 }, "indexed": { "date-parts": [ [ 2024, 11, 23 ] ], "date-time": "2024-11-23T05:32:07Z", "timestamp": 1732339927539, "version": "3.28.0" }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2024, 11, 22 ] ] }, "language": "en", "license": [ { "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 11, 22 ] ], "date-time": "2024-11-22T00:00:00Z", "timestamp": 1732233600000 } } ], "link": [ { "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/cbdv.202401947", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "311", "original-title": [], "prefix": "10.1002", "published": { "date-parts": [ [ 2024, 11, 22 ] ] }, "published-online": { "date-parts": [ [ 2024, 11, 22 ] ] }, "publisher": "Wiley", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202401947" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Uncovering the Therapeutic Potential of Propolis Extract in Managing Hyperinflammation and Long COVID‐19: A Comprehensive Bioinformatics Study", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1002/crossmark_policy" }

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