Computational Drug Design of Novel Compounds from Thymus Vulgaris Extract as Promising Candidates for Lyme disease Therapy: Targeting the OpsC Protein through Structure-Based Approaches

Lyme disease, caused by Borrelia burgdorferi, is a tick-borne disease with cases over 40,000 in the US each year. This study explores the potential of using phenolics and flavonoids derived from the Thymus vulgaris plant against the OspC protein of Lyme disease. High-performance liquid chromatography (HPLC) analysis of chloroform and n-Hexane extracts of T. vulgaris shows the presence of significant concentrations of phenolic and flavonoid compounds, including gallic acid, caffeic acid, vanillin acid, synaptic acid, quercetin, myricetin, and kaempferol. Quantitative analysis confirmed the presence of these compounds with total phenolic content (TPC) and total flavonoid content (TFC) values of 80.49 ± 0.38 and 68.9 ± 0.7 of chloroform extract. Furthermore, homology modeling of the OspC protein using SWISS-MODEL was done and validation through Ramachandran plot analysis demonstrate the stability of the protein structure, with 92.4% of amino acids residing within allowed regions. Molecular docking analysis is performed through Pyrx to assess the binding affinity of phenolic and flavonoid compounds against OspC protein. The results highlight that gallic acid exhibits strong binding affinity with a score of -7.4 and favorable ADMET properties, including a LogP value of 3.8, no violation of Lipinski's rule, and high-water solubility. Allergenicity prediction suggests that gallic acid does not induce allergic reactions, indicating its safety for use as a drug. The molecular dynamic simulation further confirms the stability of the protein, with an Eigenvalue of 2.154173e-04. The findings suggest that gallic acid exhibits strong binding affinity and favorable pharmacokinetic properties, offering a novel, plant-based natural approach for developing new Lyme disease therapeutics. Further investigations and in vivo studies are warranted to validate these findings and explore the development of novel drug candidates for the treatment of Lyme disease.