{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:01:09Z","timestamp":1773925269506,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016150","name":"Fondation OCP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016150","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Background and Objective<\/jats:title>\n                    <jats:p>\n                      While vaccination remains central to controlling the COVID-19 pandemic, the emergence of SARS-CoV-2 variants with partial resistance to immune responses has highlighted the need for complementary therapeutic strategies. Among these, antiviral agents that inhibit viral entry mechanisms are of particular interest. Animal venoms, especially scorpion venoms, are a rich source of bioactive peptides with potential antiviral properties. This study aimed to evaluate peptides derived from the Moroccan scorpion\n                      <jats:italic>Androctonus mauretanicus<\/jats:italic>\n                      as inhibitors of SARS-CoV-2 spike glycoprotein, which mediates virus entry into host cells via ACE2 receptor binding.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methodology<\/jats:title>\n                    <jats:p>\n                      Six peptides from the venom of the scorpion\n                      <jats:italic>A. mauretanicus<\/jats:italic>\n                      were first selected according to rigorous bioinformatic and experimental criteria, and their 3D structures were obtained or modeled. Their antiviral potential was then screened using the Stack-AVP stacked learning framework. The interactions of promising peptides with the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein were modeled by molecular docking using HADDOCK 2.4 and ClusPro 2.0. The most stable complexes were subjected to molecular dynamics simulations (200 ns) with GROMACS to assess their conformational stability (RMSD, Rg, RMSF) and interactions. Trajectories were analyzed by principal component analysis (PCA) and free energy landscape (FEL) construction, while binding affinity was predicted with PRODIGY.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Four peptides (AM1, AM3, AM4 and AM5) showed strong predicted antiviral activity (&amp;gt;85%). Docking identified AM5 as the most affinity ligand (\u0394G = \u221214.0 kcal\/mol), targeting the S2 fusion domain, followed by AM3 (allosteric mechanism), AM4 (targeting the furin cleavage site), and AM1 (specific RBD inhibitor). MD simulations revealed that AM1, AM3, and AM5 form structurally stable complexes (low and constant RMSD). In contrast, AM4 induces significant conformational instability (high and non-convergent RMSD) and overall decompaction. Thermodynamic analyses (FEL) confirm the superior stability of the AM3 and AM5 complexes. These results position AM5 as the most promising blocking candidate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1677524","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:42:40Z","timestamp":1772779360000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational discovery of SARS-CoV-2 viral entry inhibitory peptides from Androctonus mauretanicus scorpion venom: molecular docking and molecular dynamics simulations targeting the spike protein"],"prefix":"10.3389","volume":"6","author":[{"given":"Reda","family":"Chahir","sequence":"first","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco","place":["Casablanca, Morocco"]},{"name":"Agri-Food and Health Laboratory, Faculty of Science and Technology, Hassan First University of Settat","place":["Settat, Morocco"]}]},{"given":"Salaheddine","family":"Redouane","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics and Human Genetics, Institut Pasteur du Maroc","place":["Casablanca, Morocco"]}]},{"given":"Jacob","family":"Galan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, The University of Texas Rio Grande Valley School of Medicine","place":["Brownsville, TX, United States"]}]},{"given":"Hicham","family":"Hboub","sequence":"additional","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco","place":["Casablanca, Morocco"]},{"name":"Faculty of Medical Sciences, UM6P Hospitals, Mohammed VI Polytechnic University","place":["Benguerir, Morocco"]}]},{"given":"Lahoussaine","family":"Aserrar","sequence":"additional","affiliation":[{"name":"Laboratory of Onco-Pathology, Biology and Cancer Environment, Faculty of Medicine, University Mohammed VI of Sciences and Health","place":["Casablanca, Morocco"]}]},{"given":"Salma","family":"Chakir","sequence":"additional","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco","place":["Casablanca, Morocco"]},{"name":"Agri-Food and Health Laboratory, Faculty of Science and Technology, Hassan First University of Settat","place":["Settat, Morocco"]}]},{"given":"Ahmed Salim","family":"Lahlou","sequence":"additional","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco","place":["Casablanca, Morocco"]}]},{"given":"Hinde","family":"Aassila","sequence":"additional","affiliation":[{"name":"Agri-Food and Health Laboratory, Faculty of Science and Technology, Hassan First University of Settat","place":["Settat, Morocco"]}]},{"given":"Rachid","family":"El Fatimy","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, UM6P Hospitals, Mohammed VI Polytechnic University","place":["Benguerir, Morocco"]}]},{"given":"Naoual","family":"Oukkache","sequence":"additional","affiliation":[{"name":"Laboratory of Venoms and Toxins, Pasteur Institute of Morocco","place":["Casablanca, Morocco"]}]}],"member":"1965","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"B13","doi-asserted-by":"publisher","first-page":"15363","DOI":"10.1038\/s41598-024-65038-9","article-title":"Biomol\u00e9cules th\u00e9rapeutiques potentielles du venin d\u2019hym\u00e9nopt\u00e8res contre le SARS-CoV-2 chez des patients \u00e9gyptiens","volume":"14","author":"Abd El Maksoud","year":"2024","journal-title":"Sci. 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