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IN SILICO AND TOXICOLOGICAL EVALUATION OF OREGANO (Origanum vulgare) PHYTOCHEMICALS AS INHIBITORS OF METHIONYL-tRNA SYNTHETASE OF Brucella melitensis

Oshibanjo, Olusegun Debola, Ngurukwem, H. C., Igwe Kingsley, Oyinlola, O. O

Oshibanjo, Olusegun Debola — Department of Animal Science, Faculty of Agriculture, University of Jos, Jos, Plateau State, Nigeria (oshibanjoo@unijos.edu.ng)

Ngurukwem, H. C. — Department of Animal Science, Faculty of Agriculture, University of Jos, Jos, Plateau State, Nigeria

Igwe Kingsley — Department of Animal Science, University of Jos, Plateau state

Oyinlola, O. O — Oyo State College of Agriculture and Technology, Oyo State

Abstract

Brucellosis remains a neglected zoonosis of major veterinary and public health importance in Nigeria and across sub-Saharan Africa, and the long, relapse-prone antibiotic regimens currently in use have sustained interest in alternative antibacterial scaffolds. Methionyl-tRNA synthetase of Brucella melitensis (BmMetRS) has been experimentally validated as a drug target for the disease. This study screened ten phenolic and flavonoid constituents of oregano (Origanum vulgare) against BmMetRS and profiled their predicted pharmacokinetic and toxicological behaviour. Ligands were prepared with LigPrep and the crystal structure of BmMetRS (PDB ID: 4PY2, 2.15 Å) with the Protein Preparation Wizard in the Schrödinger Suite 2023. Docking was carried out with Glide, drug-likeness and pharmacokinetics with SwissADME, and fifteen toxicity endpoints with ProTox. All ten phytochemicals docked into the BmMetRS active site within a narrow affinity band of −6.35 to −6.59 kcal/mol, a range too small to rank the compounds reliably but sufficient to indicate that the flavonoid fraction of oregano engages the site as a class. Binding was anchored consistently at ASP 51, with MET 227, TYR 14 and TYR 228 recurring across ligands through hydrogen bonding and π–π stacking. Nine of the ten compounds showed high predicted gastrointestinal absorption, none violated Lipinski's rule of five, and bioavailability scores of 0.55–0.56 exceeded that of streptomycin (0.17). Predicted acute oral LD₅₀ values separated the compounds far more sharply than affinity did, ranging from 159 mg/kg (quercetin, class 3) to 5000 mg/kg (rosmarinic acid, class 5). Taking affinity, absorption and predicted safety together, kaempferol, apigenin, luteolin and rosmarinic acid emerged as the most balanced candidates. These are computational predictions and require in vitro confirmation, including assessment of selectivity against human methionyl-tRNA synthetase, before any therapeutic inference can be drawn.

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Publication Info

Published in: Vol. 1, No. 1 (2026)

Pages: 125 - 161

DOI: 10.xxxxx/jjaases.2026.d045f56e

License: CC-BY-4.0

OA
Open Access (CC-BY 4.0)

This article is distributed under the terms of the Creative Commons Attribution License.

Submitted: 9/15/2026

Accepted: 9/15/2026

Published: 9/19/2026

Disclosures

Funding:

No specific funding was declared for this work.

Conflict of Interest:

The authors declared no potential conflicts of interest.