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Mining therapeutic targets from the antibiotic-resistant Campylobacter coli and virtual screening of natural product inhibitors against its riboflavin synthase

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Abstract

Campylobacter coli resides in the intestine of several commonly consumed animals, as well as water and soil. It leads to campylobacteriosis when humans eat raw/undercooked meat or come into contact with infected animals. A common manifestation of the infection is fever, nausea, headache, and diarrhea. Increasing antibiotic resistance is being observed in this pathogen. The increased incidence of C. coli infection, and post-infection complications like Guillain-Barré syndrome, make it an important pathogen. It is essential to find novel therapeutic targets and drugs against it, especially with the emergence of antibiotic-resistant strains. In the current study, genomes of 89 antibiotic-resistant strains of C. coli were downloaded from the PATRIC database. Potent drug targets (n = 36) were prioritized from the core genome (n = 1,337 genes) of this species. Riboflavin synthase was selected as a drug target and pharmacophore-based virtual screening was performed to predict its inhibitors from the NPASS (n =  ~ 30,000 compounds) natural product library. The top three docked compounds (NPC115144, NPC307895, and NPC470462) were selected for dynamics simulation (for 50 ns) and ADMET profiling. These identified compounds appear safe for targeting this pathogen and can be further validated by experimental analysis before clinical trials.

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Funding

This research was supported by The Searle Company Limited (TSCL), Karachi, Pakistan.

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Authors and Affiliations

  1. HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan

    Khurshid Jalal & Diyar Ahmad

  2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan

    Kanwal Khan

  3. Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan

    Ajmal Hayat

  4. Department of Pharmaceutical Sciences, College of Pharmacy, Al-Dawadmi Campus, Shaqra University, Shaqra, Saudi Arabia

    Ghallab Alotaibi

  5. Computational Biology Unit, Lab 103 PCMD ext. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Reaz Uddin

  6. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, 61441, Saudi Arabia

    Mutaib M. Mashraqi

  7. Clinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, AlQuwayiyah, 11961, Saudi Arabia

    Ahmad Alzamami

  8. Jamil–ur–Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Muhammad Aurongzeb & Zarrin Basharat

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  1. Khurshid Jalal
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  2. Kanwal Khan
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  3. Ajmal Hayat
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  5. Ghallab Alotaibi
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  9. Muhammad Aurongzeb
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Correspondence to Muhammad Aurongzeb or Zarrin Basharat.

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Khurshid Jalal and Kanwal Khan contributed equally to this work.

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Jalal, K., Khan, K., Hayat, A. et al. Mining therapeutic targets from the antibiotic-resistant Campylobacter coli and virtual screening of natural product inhibitors against its riboflavin synthase. Mol Divers 27, 793–810 (2023). https://doi.org/10.1007/s11030-022-10455-z

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