In Silico Evaluation of Natural Compounds as Inhibitors of the Oropouche Virus Gc Glycoprotein.
Introduction: Oropouche virus (OROV) is an emerging orthobunyavirus in the Americas with no approved antiviral therapies. Methods: This work employed a structure-based in-silico pipeline to identify natural compounds with potential to inhibit the Gc glycoprotein, a class II fusion protein essential...
| Publicado en: | Salud Uninorte pp. 94 - 96 |
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| Autores principales: | , , , , , , , |
| Formato: | Artículo |
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Fundacion Universidad del Norte
2025 Special Issue
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=lth&AN=191656156&site=ehost-live header: @attributes: shortDbName: lth uiTerm: 191656156 longDbName: MedicLatina uiTag: AN controlInfo: bkinfo: jinfo: jid: 01205552 78FH jtl: Salud Uninorte issn: 01205552 maglogo: N pubinfo: dt: 2025 Special Issue pid: 15491 pub: Fundacion Universidad del Norte artinfo: ui: 191656156 10.14482/sun.01.303.867 ppf: 94 ppct: 2 formats: fmt: @attributes: type: P size: 527KB tig: atl: In Silico Evaluation of Natural Compounds as Inhibitors of the Oropouche Virus Gc Glycoprotein. aug: au: VARGAS-ECHEVERRÍA, CARLOS SAURITH-CORONELL, OSCAR RODRIGUEZ-MACÍAS, JUAN BRAZÓN, EDGAR A. MÁRQUEZ MORA, JOSÉ R. FUENTES-GANDARA, FABIO PAZ, JOSÉ L. SALAZAR, FRANKLIN affil: Department of Medicine, Health Sciences Division, Universidad del Norte, Barranquilla (Colombia) Research Group in Chemistry and Biology, Department of Chemistry and Biology, Universidad del Norte, Barranquilla (Colombia) Faculty of Health, Exact and Natural Sciences, Universidad Libre, Barranquilla (Colombia) Computational and Theoretical Chemistry Group (QCT-USFQ), Universidad San Francisco de Quito, Quito (Ecuador) Department of Natural and Exact Sciences, Universidad de la Costa, Barranquilla (Colombia) Academic Department of Inorganic Chemistry, Universidad Nacional Mayor de San Marcos, Lima (Peru) Centro de Química "Dr. Gabriel Chuchani", IVIC, Caracas (Venezuela) su: Glycoproteins Phytochemicals Bunyaviruses Virtual high-throughput screening (Drug development) Antiviral agents Molecular dynamics Molecular docking Americas sug: subj: Americas Glycoproteins Phytochemicals Bunyaviruses Virtual high-throughput screening (Drug development) Antiviral agents Molecular dynamics Molecular docking keyword: ADMET Gc glycoprotein molecular docking molecular dynamics natural compounds Oropouche virus ab: Introduction: Oropouche virus (OROV) is an emerging orthobunyavirus in the Americas with no approved antiviral therapies. Methods: This work employed a structure-based in-silico pipeline to identify natural compounds with potential to inhibit the Gc glycoprotein, a class II fusion protein essential for viral entry. Results: A curated library of 537 phytochemicals was filtered by structural similarity, selecting 20 top candidates (flavonoids and alkaloids). Molecular docking against the Gc "head" domain (PDB: 6H3X) was followed by 100-nanosecond molecular dynamics simulations in YASARA, MM-PBSA binding free energy estimations, and ADMET profiling. Quercetin, previously reported as a putative OROV inhibitor, served as the reference ligand in all dynamic analyses. Significantly, curcumin and berberine demonstrated outstanding performance, combining favorable binding energies (-38.14 and -13.10 kcal/mol, respectively) with high structural stability (RMSD ≤ 1.82 Å) throughout the simulations. Curcumin additionally exhibited a highly favorable pharmacokinetic profile, whereas berberine's potent interaction was tempered by predicted cytotoxicity and mutagenicity signals, suggesting the need for structural optimization. Cynaroside, baicalin, and naringin also maintained stable interactions, although their predicted low oral bioavailability may limit direct clinical translation. It is notable that in this model, more positive or near-zero binding energy values were interpreted as indicative of more favorable ligand-protein interactions, a criterion consistent with the evaluation algorithms implemented in YASARA, which integrates molecular mechanics with empirical force field optimizations for high-precision affinity estimation. The use of YASARA was strategic due to its robust energy minimization protocols, solvent-aware dynamics, and reproducibility over extended simulation times. Conclusions: Collectively, these findings position curcumin and berberine as highly promising molecular scaffolds for the rational development of novel antivirals against OROV, with translational potential to other emerging orthobunyaviruses. Ultimately, their performance in silico underscores the urgent need for experimental validation and paves the way for targeted antiviral discovery pipelines, a critical step in strengthening preparedness against arboviral threats in Latin America. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y custom: Copyright of Salud Uninorte is the property of Fundacion Universidad del Norte and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. item: Salud Uninorte holder: Fundacion Universidad del Norte dt: @attributes: year: 2025 holdings: @attributes: islocal: N |
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