{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:31:38Z","timestamp":1784331098508,"version":"3.55.0"},"reference-count":88,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022965","name":"Minciencias","doi-asserted-by":"crossref","award":["RC-746-2017"],"award-info":[{"award-number":["RC-746-2017"]}],"id":[{"id":"10.13039\/100022965","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oropouche virus (OROV), an emerging orthobunyavirus of increasing public health concern in the Americas, currently lacks approved antiviral therapies. In this study, we employed a structure-based in silico approach to identify natural antiviral scaffolds capable of targeting the Gc glycoprotein, a class II fusion protein essential for host membrane fusion and viral entry. A library of 537 plant-derived compounds was screened against the Gc head domain (PDB ID: 6H3X) through molecular docking and redocking, followed by 100-nanosecond molecular dynamics simulations, MM-PBSA free energy calculations, and ADMET profiling. Curcumin and Berberine emerged as standout candidates. Curcumin demonstrated a balanced profile, with stable binding (\u221238.14 kcal\/mol), low backbone RMSD (1.82 \u00c5), and consistent radius of gyration (Rg ~ 18.8 \u00c5), suggesting strong conformational stability and compactness of the protein\u2013ligand complex. Berberine exhibited the most favorable binding energy (\u221213.10 kcal\/mol) and retained dynamic stability (RMSD 1.86 \u00c5; Rg ~ 19.0 \u00c5), though accompanied by predicted cytotoxicity that may require structural refinement. Both compounds induced reduced residue-level fluctuations (RMSF &lt; 2.5 \u00c5) in functionally critical regions of the Gc protein, consistent with a mechanism of action that involves stabilization of the prefusion conformation and interference with the structural transitions required for viral entry. These findings identify curcumin and berberine as promising scaffolds for anti-OROV drug development and offer a rational foundation for future experimental validation targeting viral fusion mechanisms.<\/jats:p>","DOI":"10.3390\/ijms262110541","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T03:44:39Z","timestamp":1761795879000},"page":"10541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Structure-Based Identification of Natural Inhibitors Targeting the Gc Glycoprotein of Oropouche Virus: An In Silico Approach"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8160-3572","authenticated-orcid":false,"given":"Carlos","family":"Vargas-Echeverr\u00eda","sequence":"first","affiliation":[{"name":"Departamento de Medicina, Divisi\u00f3n Ciencias de la Salud, Universidad del Norte, Km 5, V\u00eda Puerto Colombia, Puerto Colombia 081007, Colombia"},{"name":"Grupo de Investigaciones en Qu\u00edmica y Biolog\u00eda, Departamento de Qu\u00edmica y Biolog\u00eda, Facultad de Ciencias B\u00e1sicas, Universidad del Norte, Carrera 51B, Km 5, V\u00eda Puerto Colombia, Barranquilla 081007, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4454-3126","authenticated-orcid":false,"given":"Oscar","family":"Saurith-Coronell","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Divisi\u00f3n Ciencias de la Salud, Universidad del Norte, Km 5, V\u00eda Puerto Colombia, Puerto Colombia 081007, Colombia"},{"name":"Grupo de Investigaciones en Qu\u00edmica y Biolog\u00eda, Departamento de Qu\u00edmica y Biolog\u00eda, Facultad de Ciencias B\u00e1sicas, Universidad del Norte, Carrera 51B, Km 5, V\u00eda Puerto Colombia, Barranquilla 081007, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5247-867X","authenticated-orcid":false,"given":"Juan","family":"Rodriguez-Mac\u00edas","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Exactas y Naturales, Universidad Libre, Barranquilla 080001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7503-1528","authenticated-orcid":false,"given":"Edgar A.","family":"M\u00e1rquez Braz\u00f3n","sequence":"additional","affiliation":[{"name":"Grupo de Investigaciones en Qu\u00edmica y Biolog\u00eda, Departamento de Qu\u00edmica y Biolog\u00eda, Facultad de Ciencias B\u00e1sicas, Universidad del Norte, Carrera 51B, Km 5, V\u00eda Puerto Colombia, Barranquilla 081007, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-9504","authenticated-orcid":false,"given":"Jos\u00e9 R.","family":"Mora","sequence":"additional","affiliation":[{"name":"Grupo de Qu\u00edmica Computacional y Te\u00f3rica (QCT-USFQ), Departamento de Ingenier\u00eda Qu\u00edmica, Universidad San Francisco de Quito, Diego de Robles y V\u00eda Interoce\u00e1nica, Quito 170901, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Fuentes-Gandara","sequence":"additional","affiliation":[{"name":"Department of Natural and Exact Sciences, Universidad de la Costa, Barranquilla 080003, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-7919","authenticated-orcid":false,"given":"Jos\u00e9 L.","family":"Paz","sequence":"additional","affiliation":[{"name":"Departamento Acad\u00e9mico de Qu\u00edmica Inorg\u00e1nica, Facultad de Qu\u00edmica e Ingenier\u00eda Qu\u00edmica, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin","family":"Salazar","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica \u201cDr. Gabriel Chuchani\u201d, Laboratorio de S\u00edntesis Org\u00e1nica y Productos Naturales, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sakkas, H., Bozidis, P., Franks, A., and Papadopoulou, C. 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