Core proteome mediated subtractive approach for the identification of potential therapeutic drug target against the honeybee pathogen Paenibacillus larvae .
| Autor: | Rebhi S; Université de Tunis-El Manar, Laboratoire de Mycologie, Pathologies et Biomarqueurs, Département de Biologie, Tunis, Tunisia., Basharat Z; Independent researcher, Islamabad, Pakistan., Wei CR; Department of Research and Development, Shing Huei Group, Taipei, Taiwan., Lebbal S; University of Khenchela, Department of Agricultural Sciences, Faculty of Nature and Life Sciences, Khenchela, Algeria., Najjaa H; University of Gabes, Laboratory of Pastoral Ecosystem and Valorization of Spontaneous Plants and Associated Microorganisms, Institute of Arid Lands of Medenine, Medenine, Tunisia., Sadfi-Zouaoui N; Université de Tunis-El Manar, Laboratoire de Mycologie, Pathologies et Biomarqueurs, Département de Biologie, Tunis, Tunisia., Messaoudi A; Université de Tunis-El Manar, Laboratoire de Mycologie, Pathologies et Biomarqueurs, Département de Biologie, Tunis, Tunisia.; Jendouba University, Higher Institute of Biotechnology of Beja, Beja, Tunisia. |
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| Jazyk: | angličtina |
| Zdroj: | PeerJ [PeerJ] 2024 May 27; Vol. 12, pp. e17292. Date of Electronic Publication: 2024 May 27 (Print Publication: 2024). |
| DOI: | 10.7717/peerj.17292 |
| Abstrakt: | Background & Objectives: American foulbrood (AFB), caused by the highly virulent, spore-forming bacterium Paenibacillus larvae , poses a significant threat to honey bee brood. The widespread use of antibiotics not only fails to effectively combat the disease but also raises concerns regarding honey safety. The current computational study was attempted to identify a novel therapeutic drug target against P. larvae , a causative agent of American foulbrood disease in honey bee. Methods: We investigated effective novel drug targets through a comprehensive in silico pan-proteome and hierarchal subtractive sequence analysis. In total, 14 strains of P. larvae genomes were used to identify core genes. Subsequently, the core proteome was systematically narrowed down to a single protein predicted as the potential drug target. Alphafold software was then employed to predict the 3D structure of the potential drug target. Structural docking was carried out between a library of phytochemicals derived from traditional Chinese flora ( n > 36,000) and the potential receptor using Autodock tool 1.5.6. Finally, molecular dynamics (MD) simulation study was conducted using GROMACS to assess the stability of the best-docked ligand. Results: Proteome mining led to the identification of Ketoacyl-ACP synthase III as a highly promising therapeutic target, making it a prime candidate for inhibitor screening. The subsequent virtual screening and MD simulation analyses further affirmed the selection of ZINC95910054 as a potent inhibitor, with the lowest binding energy. This finding presents significant promise in the battle against P. larvae. Conclusions: Computer aided drug design provides a novel approach for managing American foulbrood in honey bee populations, potentially mitigating its detrimental effects on both bee colonies and the honey industry. Competing Interests: Zarrin Basharat is an Academic Editor for PeerJ. Calvin R. Wei is employed by Shing Huei Group. (©2024 Rebhi et al.) |
| Databáze: | MEDLINE |
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