{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:52:40Z","timestamp":1776333160460,"version":"3.51.2"},"reference-count":107,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Hepatitis B virus (HBV) infection continues to be a major public health concern, especially in sub-Saharan Africa, where widespread epidemics and restricted availability of long-term antiviral therapies result in higher mortality and morbidity rates. Drug repurposing represents a strategic approach to accelerate the discovery of effective therapies by leveraging agents with demonstrated antiviral and immunomodulatory activity. Product Nkabinde (PN) is a patented African polyherbal formulation initially developed for the treatment of HIV. Recent experimental studies demonstrate PN\u2019s potent anti-HIV activity and significant immunomodulatory effects in human immune cells, implicating host-directed mechanisms relevant to chronic viral infections. This study combines an integrative application of network pharmacology and molecular docking to evaluate the repurposing potential of PN as a multi-target agent in HBV. Method: Bioactive components of PN were screened, and compound-associated targets were intersected with HBV-associated genes (proteins) to construct a protein\u2013protein interaction (PPI) network. Topological analysis identified 10 hub targets (STAT1, STAT3, SRC, HCK, EGFR, SYK, PIK3CA, PIK3CB, PIK3R1, and PTPN11). Gene Ontology and KEGG pathway enrichment were performed with an FDR cut-off &lt; 0.05. Significantly enriched pathways included JAK\u2013STAT signaling, chemokine signaling, EGFR-TKI resistance, PI3K complex signaling, and viral infection pathways, particularly those related to Kaposi sarcoma virus and HSV-1, indicating immunoregulatory and antiviral roles. Molecular docking was performed using AutoDock Vina 1.1.2 to evaluate binding affinity and interaction mode of key PN phytochemicals against the hub proteins, and results were compared to their respective co-crystallized ligands. Results: Molecular docking indicated that major phytochemicals from PN exhibited significant binding affinities across all 10 hub host targets, typically outperforming or closely matching their respective co-crystallized ligands. The strongest contacts were observed for \u03b2-sitosterol\u2013PIK3CB (\u221214.2 kcal\/mol) and oleanolic acid\u2013SYK (\u221214.0 kcal\/mol), which were significantly stronger than the co-crystallized ligands (\u22127.9 and \u22128.3 kcal\/mol, respectively), indicating robust stabilization within catalytic and regulatory pockets. Procyanidin B2 toward HCK (\u221210.5 vs. \u22127.9 kcal\/mol) and PIK3CA (\u22129.5 vs. \u22127.3 kcal\/mol), quercetin toward PIK3R1 (\u221210.6 vs. \u22128.2 kcal\/mol) and PTPN11 (\u22129.2 vs. \u22127.5 kcal\/mol), rutin toward SRC (\u221210.5 vs. 7.8 kcal\/mol), and diosgenin toward EGFR (\u22129.4 vs. 8.4 kcal\/mol). Procyanidin B2 maintained robust multi-hydrogen bonding networks, demonstrating significant binding, despite STAT1 and STAT3 docking showing identical affinities to co-crystals. Conserved hydrogen bonds, \u03c0\u2013cation interactions, and significant hydrophobic packing at ATP-binding clefts and regulatory domains supported these interaction patterns, indicating competitive suppression of host signaling nodes taken over by HBV. Conclusions: Together, these results demonstrate that the components of PN possess strong multitarget binding capabilities across the PI3K\/AKT, JAK\u2013STAT, SRC-family kinase, EGFR, and SYK pathways, supporting their potential repurposing as host-directed HBV therapeutics with the ability to impede immune evasion, viral persistence, and HBV-associated oncogenic progression.<\/jats:p>","DOI":"10.3390\/ph19040627","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:04:42Z","timestamp":1776330282000},"page":"627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing Product Nkabinde for Hepatitis B Virus Therapy: A Network Pharmacology and Molecular Docking Investigation"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1856-5697","authenticated-orcid":false,"given":"Samuel Chima","family":"Ugbaja","sequence":"first","affiliation":[{"name":"Traditional Medicine, School of Medicine, University of KwaZulu Natal, Durban 4000, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siphathimandla Authority","family":"Nkabinde","sequence":"additional","affiliation":[{"name":"Traditional Medicine, School of Medicine, University of KwaZulu Natal, Durban 4000, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magugu","family":"Nkabinde","sequence":"additional","affiliation":[{"name":"Traditional Medicine, School of Medicine, University of KwaZulu Natal, Durban 4000, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nceba","family":"Gqaleni","sequence":"additional","affiliation":[{"name":"Traditional Medicine, School of Medicine, University of KwaZulu Natal, Durban 4000, South Africa"},{"name":"African Health Research Institute (AHRI), 719 Umbilo Road, Durban 4001, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e079579","DOI":"10.1136\/bmj-2024-079579","article-title":"Advances in the Management of Hepatitis B","volume":"389","author":"Rajbhandari","year":"2025","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Shechter, O., Sausen, D.G., Dahari, H., Vaillant, A., Cotler, S.J., and Borenstein, R. 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