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2000
Volume 28, Issue 15
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Introduction

This study aimed to identify marine-derived protease inhibitors with potential applications in immunogenicity-targeted therapies.

Methods

Starting with a pharmacophore model based on the GRL-09510 complex (PDB ID: 5v4y), we isolated three critical features (RAA) that facilitated the selection of 192 candidates from an initial pool of 18,547 compounds.

Results

Subsequent docking analyses, validated with a strong ROC value of 0.74, revealed four high-affinity compounds: Echoside C (CMNPD22461), Anguibactin (CMNPD3610), Hansforester K (CMNPD30598), and Polyandocarpamide A (CMNPD4564), with binding scores of -7.773, -7.770, -7.690, and -7.236 kcal/mol, respectively—each exceeding the reference compound's binding efficacy. Further assessments of drug-likeness (ADME) and toxicity profiles produced favorable results and predicted biological activity from the PASS program supported their potential as potent protease inhibitors. Density Functional Theory (DFT) analysis and molecular dynamics simulations confirmed the stability of these compounds when bound to the protease’s active site, with configurations similar to the GRL-09510 complex.

Conclusion

These findings suggest that the identified marine-derived compounds hold significant promise as effective protease inhibitors, offering new opportunities for immunotherapy and advancements in drug development.

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An Integrated Computational Approach to Identify Potent HIV-1 Protease Inhibitors from Marine Sources
Comb Chem High Throughput Screen 28, 2704 (2025); https://doi.org/10.2174/0113862073344783241205075752
/content/journals/cchts/10.2174/0113862073344783241205075752
/content/journals/cchts/10.2174/0113862073344783241205075752
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  • Article Type:     Research Article
Keyword(s): density functional theory; HIV-1 PR; molecular docking; molecular dynamics; pharmacophore

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