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

Abstract

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.

Identification, Synthesis, and In Vitro Activities of Antimicrobial Peptide from African Catfish against the Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli

“…When compared to the activity of earlier reported fish mucosal AMPs on other bacterial strains, NACAP-II demonstrated a lower MIC compared to ACAP-IV (MIC 520.7 µg/mL) from the wild African catfish, Clarias garienpinus [17]. However, its value was slightly higher than that a Goldenstriped soapfish-derived peptide Gs D (FIGGIISFFKRLF) (MIC, 13.3-50 µg/mL) [42] and that of Pelteobagrin (GKLNLFLSRLEILKLFVGAL) sourced from the yellow catfish, Pelteobagrus fulvidraco (MIC, 2-64 µg/mL) [43].…”

“…On par with earlier reported fish-derived mucosal AMPs like Myxinidin [25] and peptide ACAP-V [18], peptide NACAP-II was cationic (+2), possibly justifying its action on ESBL-producing E. coli. On the other hand, the modeled structure NACAP-II peptide was found to be less stable when compared to the ACAP-IV peptide from wild African catfish that had all its residues (100.0%) for both I-TASSER and PEP-FOLD in the most favored regions [17].…”

“…The African catfish, Clarias gariepinus is a benthopelagic freshwater scale-less fish [15], and their skin mucus is endowed with antimicrobial peptides (AMPs) [16][17][18]. With a generally recognized as safe (GRAS) status [19], broad-spectrum [20,21], rapid action [22], short length [19] AMPs are considered a promising fountain of novel antimicrobial drug candidates.…”

“…Despite these potentials, no published record exists on the structure and safety profiles of AMPs in farmed African catfish. Moreover, our previous studies solely focused on the structure and potency of mucosal AMPs from wild African catfish [16][17][18] leaving the need to compare such attributes, especially the antimicrobial activity of mucosal AMPs of farmed African fish. Thus, in the quest for potential drug leads against ESBL-producing bacteria, the current study presents findings on the structure, in vitro activities, and safety antimicrobial peptides in the skin mucus of farmed African catfish.…”

An Integrated Comprehensive Peptidomics and In Silico Analysis of Bioactive Peptide-Rich Milk Fermented by Three Autochthonous Cocci Strains

“…During the development process of a new therapeutic drug, it is of utmost importance to know the fate of pharmacokinetics, i.e., the fate of a compound in the organism, as poor pharmacokinetic properties are one of the main causes of failures during clinical phases, in addition to a lack of efficacy and unacceptable toxicity [76]. This is usually established via individual indices called absorption, distribution, metabolism, excretion and toxicity (AD-MET) parameters, which are usually determined using in silico modelling as an alternative to experimental methods.…”