{
  "abstract": "Dengue virus serotype 2 is a human pathogenic flavivirus encoding non-structural protein 3 (DEN2-NS3), a superfamily-2 viral helicase. DEN2-NS3 contains an N-terminal protease domain and a C-terminal RNA helicase/nucleoside 5'-triphosphatase (NTPase) domain essential for replication. The enzyme utilizes energy from NTP hydrolysis to translocate 3'-to-5' along a duplex RNA substrate. Prompted by the high potency of (--)-epigallocatechin gallate (EGCG) against Zika virus, this study investigated if three catechins, EGCG, (--)-epicatechin gallate (ECG), and (--)-epigallocatechin (EGC), would be potent inhibitors of DEN2-NS3. Enzyme-inhibition assays demonstrated that the catalytic domain, DEN2-NS3(S171-K618), was strongly inhibited by the galloylated catechins (EGCG and ECG), verified by an enzyme-coupled confirmatory assay. Inhibition constants (Ki) and suggestive inhibition modes relative to NTPase activity were Ki = 400 {+/-} 86.6 nM for EGCG (mixed-mode), Ki = 550 {+/-} 250 nM for ECG (uncompetitive), and Ki = 18.3 {+/-} 4.2 {micro}M for EGC (mixed-mode). The coronavirus inhibitor SSYA10-001 inhibited DEN2-NS3 (Ki = 10.2 {+/-} 0.3 {micro}M, mixed-mode). Computational workflows using SiteMap identified a predicted druggable pocket associated with the RNA-binding region, involving residues ASP290, ARG387, ASP409, MET429, HIS487, ASP541, ARG599, and ASP603. Catechins were analyzed through 200-ns molecular dynamics simulations to evaluate binding stability. Computational results revealed that EGCG and ECG maintained high stability, forming highly persistent shared amino acid contacts (>45% occupancy) with ASP603, ARG599, ASP541, and ARG387. Biochemical and computational data support these galloylated catechin leads, suggesting a plausible binding model within an amphipathic pocket. Future structural optimization into stable prodrug derivatives could yield promising antiviral candidates.",
  "abstract_shown": true,
  "affiliations": [
    "University of South Carolina Beaufort"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "M. K. Wojciechowski"
    },
    {
      "name": "L. D. Goyzueta-Mamani"
    },
    {
      "name": "M. A. Chavez-Fumagalli"
    },
    {
      "affs": [
        0
      ],
      "name": "E. L. D'Antonio"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3krg8pzqr9thy.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.06.22.733882",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.06.22.733882v3.full",
  "id": "3krg8pzqr9thy",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.06.22.733882v3",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "2739|Mosquito-borne diseases and control"
    ]
  ],
  "openalex": "W7165679941",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.06.22.733882v3.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3krg8pzqr9thy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:42Z",
      "native_id": "10.64898/2026.06.22.733882",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.06.22.733882v3"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Mosquito-borne diseases and control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Targeting Dengue Virus NS3 Helicase: Biochemical and Computational Evaluation of Catechins from Camellia sinensis as Potential Therapeutic Leads",
  "title_text": "Targeting Dengue Virus NS3 Helicase: Biochemical and Computational Evaluation of Catechins from Camellia sinensis as Potential Therapeutic Leads",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:42Z",
  "url": "https://research.draconitic.com/paper/3krg8pzqr9thy",
  "venue": "bioRxiv",
  "versions": []
}