Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections
Intracellular bacterial infections pose a significant challenge to current therapeutic strategies due to the limited penetration of antibiotics through host cell membranes. This study presents a novel computational framework for efficiently screening candidate peptides against these infections. The...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2025-08-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25001550 |
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| author | Yanpeng Fang Duoyang Fan Bin Feng Yingli Zhu Ruyan Xie Xiaorong Tan Qianhui Liu Jie Dong Wenbin Zeng |
| author_facet | Yanpeng Fang Duoyang Fan Bin Feng Yingli Zhu Ruyan Xie Xiaorong Tan Qianhui Liu Jie Dong Wenbin Zeng |
| author_sort | Yanpeng Fang |
| collection | DOAJ |
| description | Intracellular bacterial infections pose a significant challenge to current therapeutic strategies due to the limited penetration of antibiotics through host cell membranes. This study presents a novel computational framework for efficiently screening candidate peptides against these infections. The proposed strategy comprehensively evaluates the essential properties for the clinical application of candidate peptides, including antimicrobial activity, permeation efficiency, and biocompatibility, while also taking into account the speed and reliability of the screening process. A combination of multiple AI-based activity prediction models allows for a thorough assessment of sequences in the cell-penetrating peptides (CPPs) database and quickly identifies candidate peptides with target properties. On this basis, the CPP microscopic dynamics research system was constructed. Exploration of the mechanism of action at the atomic level provides strong support for the discovery of promising candidate peptides. Promising candidates are subsequently validated through in vitro and in vivo experiments. Finally, Crot-1 was rapidly identified from the CPPsite 2.0 database. Crot-1 effectively eradicated intracellular MRSA, demonstrating significantly greater efficacy than vancomycin. Moreover, it exhibited no apparent cytotoxicity to host cells, highlighting its potential for clinical application. This work offers a promising new avenue for developing novel antimicrobial materials to combat intracellular bacterial infections. |
| format | Article |
| id | doaj-art-0a2128eda8294b72b026654ca3cc935a |
| institution | DOAJ |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-0a2128eda8294b72b026654ca3cc935a2025-08-20T03:20:15ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-08-015051052410.1016/j.bioactmat.2025.04.016Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infectionsYanpeng Fang0Duoyang Fan1Bin Feng2Yingli Zhu3Ruyan Xie4Xiaorong Tan5Qianhui Liu6Jie Dong7Wenbin Zeng8Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha 410078, PR ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha 410078, PR ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha 410078, PR ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha 410078, PR ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha 410078, PR ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha 410078, PR ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha 410078, PR ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha 410078, PR China; Corresponding author. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China.Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha 410078, PR China; Corresponding author. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, PR China.Intracellular bacterial infections pose a significant challenge to current therapeutic strategies due to the limited penetration of antibiotics through host cell membranes. This study presents a novel computational framework for efficiently screening candidate peptides against these infections. The proposed strategy comprehensively evaluates the essential properties for the clinical application of candidate peptides, including antimicrobial activity, permeation efficiency, and biocompatibility, while also taking into account the speed and reliability of the screening process. A combination of multiple AI-based activity prediction models allows for a thorough assessment of sequences in the cell-penetrating peptides (CPPs) database and quickly identifies candidate peptides with target properties. On this basis, the CPP microscopic dynamics research system was constructed. Exploration of the mechanism of action at the atomic level provides strong support for the discovery of promising candidate peptides. Promising candidates are subsequently validated through in vitro and in vivo experiments. Finally, Crot-1 was rapidly identified from the CPPsite 2.0 database. Crot-1 effectively eradicated intracellular MRSA, demonstrating significantly greater efficacy than vancomycin. Moreover, it exhibited no apparent cytotoxicity to host cells, highlighting its potential for clinical application. This work offers a promising new avenue for developing novel antimicrobial materials to combat intracellular bacterial infections.http://www.sciencedirect.com/science/article/pii/S2452199X25001550Intracellular bacterial infectionArtificial intelligenceCell-penetrating peptideMolecular dynamics simulationAntimicrobial peptide |
| spellingShingle | Yanpeng Fang Duoyang Fan Bin Feng Yingli Zhu Ruyan Xie Xiaorong Tan Qianhui Liu Jie Dong Wenbin Zeng Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections Bioactive Materials Intracellular bacterial infection Artificial intelligence Cell-penetrating peptide Molecular dynamics simulation Antimicrobial peptide |
| title | Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections |
| title_full | Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections |
| title_fullStr | Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections |
| title_full_unstemmed | Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections |
| title_short | Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections |
| title_sort | harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections |
| topic | Intracellular bacterial infection Artificial intelligence Cell-penetrating peptide Molecular dynamics simulation Antimicrobial peptide |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25001550 |
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