ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus

Amidst rising cases of antimicrobial resistance, antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics. Even so, poor pharmacokinetic profiles of certain AMPs impede their utility necessitating, a careful assessment of potential AMPs’ absorption, distributi...

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Main Authors: Okella, H., Okello, E., Mtewa, A.G., Ikiriza, H., Kaggwa, B., Aber, J., Ndekezi, C., Nkamwesiga, Joseph, Ajayi, C.O., Mugeni, I.M., Ssentamu, G., Ochwo, S., Odongo, S., Tolo, C.U., Kato, C.D., Engeu, P.O.
Format: Journal Article
Language:Inglés
Published: Frontiers Media 2022
Subjects:
Online Access:https://hdl.handle.net/10568/125848
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author Okella, H.
Okello, E.
Mtewa, A.G.
Ikiriza, H.
Kaggwa, B.
Aber, J.
Ndekezi, C.
Nkamwesiga, Joseph
Ajayi, C.O.
Mugeni, I.M.
Ssentamu, G.
Ochwo, S.
Odongo, S.
Tolo, C.U.
Kato, C.D.
Engeu, P.O.
author_browse Aber, J.
Ajayi, C.O.
Engeu, P.O.
Ikiriza, H.
Kaggwa, B.
Kato, C.D.
Mtewa, A.G.
Mugeni, I.M.
Ndekezi, C.
Nkamwesiga, Joseph
Ochwo, S.
Odongo, S.
Okella, H.
Okello, E.
Ssentamu, G.
Tolo, C.U.
author_facet Okella, H.
Okello, E.
Mtewa, A.G.
Ikiriza, H.
Kaggwa, B.
Aber, J.
Ndekezi, C.
Nkamwesiga, Joseph
Ajayi, C.O.
Mugeni, I.M.
Ssentamu, G.
Ochwo, S.
Odongo, S.
Tolo, C.U.
Kato, C.D.
Engeu, P.O.
author_sort Okella, H.
collection Repository of Agricultural Research Outputs (CGSpace)
description Amidst rising cases of antimicrobial resistance, antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics. Even so, poor pharmacokinetic profiles of certain AMPs impede their utility necessitating, a careful assessment of potential AMPs’ absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties during novel lead exploration. Accordingly, the present study utilized ADMET scores to profile seven previously isolated African catfish antimicrobial peptides (ACAPs). After profiling, the peptides were docked against approved bacterial protein targets to gain insight into their possible mode of action. Promising ACAPs were then chemically synthesized, and their antibacterial activity was validated in vitro utilizing the broth dilution method. All seven examined antimicrobial peptides passed the ADMET screening, with two (ACAP-IV and ACAP-V) exhibiting the best ADMET profile scores. The ACAP-V had a higher average binding energy (−8.47 kcal/mol) and average global energy (−70.78 kcal/mol) compared to ACAP-IV (−7.60 kcal/mol and −57.53 kcal/mol), with the potential to penetrate and disrupt bacterial cell membrane (PDB Id: 2w6d). Conversely, ACAP-IV peptide had higher antibacterial activity against E. coli and S. aureus (Minimum Inhibitory Concentration, 520.7 ± 104.3 μg/ml and 1666.7 ± 416.7 μg/ml, respectively) compared to ACAP-V. Collectively, the two antimicrobial peptides (ACAP-IV and ACAP-V) are potential novel leads for the food, cosmetic and pharmaceutical industries. Future research is recommended to optimize the expression of such peptides in biological systems for extended evaluation.
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spelling CGSpace1258482025-12-08T10:29:22Z ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus Okella, H. Okello, E. Mtewa, A.G. Ikiriza, H. Kaggwa, B. Aber, J. Ndekezi, C. Nkamwesiga, Joseph Ajayi, C.O. Mugeni, I.M. Ssentamu, G. Ochwo, S. Odongo, S. Tolo, C.U. Kato, C.D. Engeu, P.O. antimicrobial resistance fish Amidst rising cases of antimicrobial resistance, antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics. Even so, poor pharmacokinetic profiles of certain AMPs impede their utility necessitating, a careful assessment of potential AMPs’ absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties during novel lead exploration. Accordingly, the present study utilized ADMET scores to profile seven previously isolated African catfish antimicrobial peptides (ACAPs). After profiling, the peptides were docked against approved bacterial protein targets to gain insight into their possible mode of action. Promising ACAPs were then chemically synthesized, and their antibacterial activity was validated in vitro utilizing the broth dilution method. All seven examined antimicrobial peptides passed the ADMET screening, with two (ACAP-IV and ACAP-V) exhibiting the best ADMET profile scores. The ACAP-V had a higher average binding energy (−8.47 kcal/mol) and average global energy (−70.78 kcal/mol) compared to ACAP-IV (−7.60 kcal/mol and −57.53 kcal/mol), with the potential to penetrate and disrupt bacterial cell membrane (PDB Id: 2w6d). Conversely, ACAP-IV peptide had higher antibacterial activity against E. coli and S. aureus (Minimum Inhibitory Concentration, 520.7 ± 104.3 μg/ml and 1666.7 ± 416.7 μg/ml, respectively) compared to ACAP-V. Collectively, the two antimicrobial peptides (ACAP-IV and ACAP-V) are potential novel leads for the food, cosmetic and pharmaceutical industries. Future research is recommended to optimize the expression of such peptides in biological systems for extended evaluation. 2022-12-08 2022-12-08T13:40:16Z 2022-12-08T13:40:16Z Journal Article https://hdl.handle.net/10568/125848 en Open Access Frontiers Media Okella, H., Okello, E., Mtewa, A.G., Ikiriza, H., Kaggwa, B., Aber, J., Ndekezi, C., Nkamwesiga, J., Ajayi, C.O., Mugeni, I.M., Ssentamu, G., Ochwo, S., Odongo, S., Tolo, C.U., Kato, C.D. and Engeu, P.O. 2022. ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus. Frontiers in Molecular Biosciences 9: 1039286.
spellingShingle antimicrobial resistance
fish
Okella, H.
Okello, E.
Mtewa, A.G.
Ikiriza, H.
Kaggwa, B.
Aber, J.
Ndekezi, C.
Nkamwesiga, Joseph
Ajayi, C.O.
Mugeni, I.M.
Ssentamu, G.
Ochwo, S.
Odongo, S.
Tolo, C.U.
Kato, C.D.
Engeu, P.O.
ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus
title ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus
title_full ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus
title_fullStr ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus
title_full_unstemmed ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus
title_short ADMET profiling and molecular docking of potential antimicrobial peptides previously isolated from African catfish, Clarias gariepinus
title_sort admet profiling and molecular docking of potential antimicrobial peptides previously isolated from african catfish clarias gariepinus
topic antimicrobial resistance
fish
url https://hdl.handle.net/10568/125848
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