School of Medicine Publications
Document Type
Article
Publication Date
3-5-2026
Abstract
Background and Objective:
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 Androctonus mauretanicus as inhibitors of SARS-CoV-2 spike glycoprotein, which mediates virus entry into host cells via ACE2 receptor binding.
Material and Methodology:
Six peptides from the venom of the scorpion A. mauretanicus 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.
Results:
Four peptides (AM1, AM3, AM4 and AM5) showed strong predicted antiviral activity (>85%). Docking identified AM5 as the most affinity ligand (ΔG = −14.0 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.
Recommended Citation
Chahir, R., Redouane, S., Galan, J., Hboub, H., Aserrar, L., Chakir, S., Lahlou, A. S., Aassila, H., El Fatimy, R., & Oukkache, N. (2026). 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. Frontiers in Bioinformatics, 6. https://doi.org/10.3389/fbinf.2026.1677524
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Frontiers in Bioinformatics
DOI
10.3389/fbinf.2026.1677524
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
© 2026 Chahir, Redouane, Galan, Hboub, Aserrar, Chakir, Lahlou, Aassila, El Fatimy and Oukkache.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.