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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.
6 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, MproB,1, and RNA-dependent RNA polymeraseC,1 proteins. Propolis may inhibit spike protein and ACE2 interaction4, may inhibit SARS-CoV-2 through interactions with MAPK13, inhibited SARS-CoV-2 in Vero E6 cells at a concentration comparable to a combination of four antiviral components5, may mitigate hyperinflammation via STAT1, NOS2, and BTK targeting2, and may suppress Epstein-Barr Virus reactivation2.
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.
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 PaperPropolisAll
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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>', 'DOI': '10.1002/cbdv.202401947', 'type': 'journal-article', 'created': { 'date-parts': [[2024, 11, 22]], 'date-time': '2024-11-22T14:04:14Z', 'timestamp': 1732284254000}, 'update-policy': 'http://dx.doi.org/10.1002/crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Uncovering the Therapeutic Potential of Propolis Extract in Managing Hyperinflammation and Long ' 'COVID‐19: A Comprehensive Bioinformatics Study', 'prefix': '10.1002', 'author': [ { 'given': 'Isa', 'family': 'Anshori', 'sequence': 'first', 'affiliation': [ { 'name': 'Institut Teknologi Bandung School of Electrical Engineering and ' 'Informatics Jl. Ganesa No. 10 40132 Bandung INDONESIA'}]}, { 'given': 'Donny', 'family': 'Marcius', 'sequence': 'additional', 'affiliation': [ { 'name': 'Institut Teknologi Bandung School of Electrical Engineering and ' 'Informatics Jalan Ganeca 10 Bandung 40132 Bandung INDONESIA'}]}, { 'given': 'Putri Hawa', 'family': 'Syaifie', 'sequence': 'additional', 'affiliation': [ { 'name': 'Nano Center Indonesia Nano Center Indonesia Jalan PUSPIPTEK ' '15314 South Tangerang INDONESIA'}]}, { 'given': 'Khalish Arsy Al Khairy', 'family': 'Siregar', 'sequence': 'additional', 'affiliation': [ { 'name': 'Universitas Muhammadiyah Kalimantan Timur Faculty of Pharmacy ' 'Jl. Ir. H. Juanda No.15 75124 Samarinda INDONESIA'}]}, { 'given': 'Luqman Abdan', 'family': 'Syakuran', 'sequence': 'additional', 'affiliation': [ { 'name': 'Nano Center Indonesia Nano Center Indonesia Jalan PUSPIPTEK ' 'South Tangerang 15314 South Tangerang INDONESIA'}]}, { 'given': 'Muhammad Miftah', 'family': 'Jauhar', 'sequence': 'additional', 'affiliation': [ { 'name': 'Nano Center Indonesia Nano Center Indonesia Jalan PUSPIPTEK ' 'South Tangerang 15314 South Tangerang INDONESIA'}]}, { 'given': 'Adzani Gaisani', 'family': 'Arda', 'sequence': 'additional', 'affiliation': [ { 'name': 'Nano Center Indonesia Nano Center Indonesia Jalan PUSPIPTEK ' 'South Tangerang 15314 South Tangerang INDONESIA'}]}, { 'given': 'Wervyan', 'family': 'Shalannanda', 'sequence': 'additional', 'affiliation': [ { 'name': 'Institut Teknologi Bandung School of Electrical Engineering and ' 'Informatics Jalan Ganeca 10 40132 Bandung INDONESIA'}]}, { 'given': 'Etik', 'family': 'Mardliyati', 'sequence': 'additional', 'affiliation': [ { 'name': 'National Research and Innovation Agency Republic of Indonesia ' 'Research Center for Vaccine and Drug Jalan Raya Bogor 16911 ' 'Cibinong INDONESIA'}]}], 'member': '311', 'published-online': {'date-parts': [[2024, 11, 22]]}, 'container-title': 'Chemistry &amp; Biodiversity', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://onlinelibrary.wiley.com/doi/pdf/10.1002/cbdv.202401947', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 11, 22]], 'date-time': '2024-11-22T14:04:16Z', 'timestamp': 1732284256000}, 'score': 1, 'resource': {'primary': {'URL': 'https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202401947'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 11, 22]]}, 'references-count': 0, 'alternative-id': ['10.1002/cbdv.202401947'], 'URL': 'http://dx.doi.org/10.1002/cbdv.202401947', 'relation': {}, 'ISSN': ['1612-1872', '1612-1880'], 'subject': [], 'container-title-short': 'Chemistry &amp; Biodiversity', 'published': {'date-parts': [[2024, 11, 22]]}, 'assertion': [ { 'value': '2024-08-13', 'order': 0, 'name': 'received', 'label': 'Received', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2024-11-19', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2024-11-22', 'order': 3, 'name': 'published', 'label': 'Published', 'group': {'name': 'publication_history', 'label': 'Publication History'}}]}
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