Peptide-based drug as atherosclerosis multitarget therapy from Lytechinus variegatus spine: An in silico study

Authors

  • Dessy Arisanty Department of Biochemistry, Faculty of Medicine, Universitas Andalas, Padang, Indonesia; Department of Biomedical Science, Faculty of Medicine, Universitas Andalas, Padang, Indonesia
  • Salsabila P. Khairani Department of Biomedical Science, Faculty of Medicine, Universitas Andalas, Padang, Indonesia https://orcid.org/0000-0001-5460-2312
  • Kevin Nathaniel Department of Medicine, Faculty of Medicine, Universitas Andalas, Padang, Indonesia https://orcid.org/0009-0007-7785-7474
  • Dhyani P. Wahyudi Department of Medicine, Faculty of Medicine, Universitas Pembangunan Nasional Veteran Jakarta, Jakarta, Indonesia https://orcid.org/0009-0002-6534-0164
  • Isna C. Kamila Department of Medicine, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia https://orcid.org/0009-0008-1070-3267
  • Malya CS. Maharani Department of Medicine, Faculty of Medicine, Universitas Pembangunan Nasional Veteran Jakarta, Jakarta, Indonesia
  • Eillen Theodora Department of Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia https://orcid.org/0009-0000-8462-5435
  • Raymond E. Budianto Department of Medicine, Faculty of Medicine, Universitas Udayana, Denpasar, Indonesia https://orcid.org/0000-0001-6889-1266
  • Alifya R. Shofiy Department of Medicine, Faculty of Medicine, Universitas Pembangunan Nasional Veteran Jakarta, Jakarta, Indonesia
  • Ikwandi C. Nugraha Department of Medicine, Faculty of Medicine and Health, Universitas Muhammadiyah, Makassar, Indonesia https://orcid.org/0009-0004-7455-0758
  • Zaki S. Aaliyya Department of Medicine, Faculty of Medicine, Universitas Jenderal Soedirman, Banyumas, Indonesia https://orcid.org/0009-0006-1537-2175
  • Awalil RK. Rahman Department of Medicine, Faculty of Medicine, Universitas Pembangunan Nasional Veteran Jakarta, Jakarta, Indonesia https://orcid.org/0009-0004-8950-8931
  • Al H. Ariouso Department of Medicine, Faculty of Medicine, Universitas Mataram, Mataram, Indonesia https://orcid.org/0009-0003-5063-647X

DOI:

https://doi.org/10.52225/narra.v5i2.1152

Keywords:

Atherosclerosis, Lytechinus variegatus, molecular docking, peptide-based drug, multitarget therapy

Abstract

Atherosclerosis is a leading cardiovascular disease characterized by the buildup of plaques within arterial walls. The aim of this study was to investigate the potential of peptides derived from Lytechinus variegatus spines as novel therapeutic agents for atherosclerosis using an in silico approach. Key proteins involved in atherosclerosis were selected as target proteins: vascular endothelial growth factor receptor (VEGFR), protein kinase B (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 8 (MAPK8), and endothelin-1 (ET-1). Comprehensive analysis involving ligand and protein preparation, toxicity, and allergenicity assessments, absorption, distribution, metabolism and excretion (ADME) predictions, and molecular docking were conducted to evaluate the safety, pharmacokinetic properties, binding affinity (kcal/mol), root mean square deviation (RMSD) (Å), as well as a 2D and 3D visualization. Toxicity predictions revealed that peptide 9 was non-toxic and non-allergenic, with a lethal dose 50 (LD50) of 3,000 mg/kg, indicating its safety. Peptide 9 demonstrated the most promising results, effectively inhibiting VEGFR2 (-10,90 kcal/mol), AKT1 (-10,56 kcal/mol), EGFR (-9,82 kcal/mol), MAPK8 (-9,64 kcal/mol), and ET-1 (-11,41 kcal/mol) with strong binding affinities and specificity. These interactions suggested that peptide 9 from Lytechinus variegatus spines may serve as a competitive multitarget inhibitor, offering potential multitarget therapeutic activity against atherosclerosis. Peptide 9 also had high water solubility and did not affect the concentration or excretion of other drugs or compounds, minimizing the risk of drug-drug interactions.

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