Therapeutics Potential of Chlorella sorokiniana Bioactives against Sulphur Ester Dioxygenase (4CVY) in Multidrug-resistant Mycobacterium tuberculosis

Abstract

Introduction: Multidrug-resistant tuberculosis (MDR-TB) disease is caused by Mycobacterium tuberculosis that are resistant to at least one of the most effective TB medicines (Isoniazid and Rifampicin) used in treatment regimens. It remains one of the deadliest infectious diseases and a  major threat to the health sector globally. The enzyme sulfur ester dioxygenase (PDB ID: 4CVY crystal structure) plays a crucial role in its survival and virulence by reducing sulfate to sulfide. Thus, it helps the organism obtain essential sulfur for growth. Meanwhile, Chlorella sorokiniana, a microalga has a significant biotechnological potential in combatting MDR-TB due to its rich nutritional profile and bioactive compounds. Aim: This study was undertaken to investigate the therapeutic potential of bioactive compounds from Chlorella sorokiniana as novel drug candidates targeting the sulfur ester dioxygenase enzyme (PDB ID: 4CVY), a key factor in the survival and virulence of multidrug-resistant Mycobacterium tuberculosis. Study Design: This study employed a laboratory-based experimental approach completed with insilico analyses involving the use of molecular docking tools. Place and Duration of Study: This research was conducted at the Microbial Resources Research Laboratory, Department of Pure and Applied Biology, Ladoke Akintola University of Technology Ogbomoso, Nigeria over a twelve-month period from January 2024 to December 2024. Methodology: Water Samples were collected from different fish ponds located at Randa, Taki Area, Ogbomoso, Oyo State, Nigeria. Chlorella sorokiniana was isolated from the pond water samples obtained from the fish pond and subsequently cultivated in Bristol medium broth under controlled laboratory conditions with exposure to natural light at an ambient temperature of 30 ± 2 °C for 2–3 weeks. The resulting metabolites were characterized and subjected to phytochemical analysis. Gas Chromatography–Mass Spectrometry (GC-MS; GC-MS QP instrument) was used to identify the present bioactive compounds, while Fourier Transform Infrared Spectroscopy (FTIR) was used to confirm the presence of functional groups, including hydroxyl, carbonyl, and amine groups, which are known to contribute to bioactivity. Molecular docking studies of the identified metabolites were performed against the target protein sulfur ester dioxygenase (PDB ID: 4CVY) using PyRx software.  Isoniazid, a first-line anti-tuberculosis drug, was employed as a reference drug standard. Furthermore, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of the bioactive compounds were predicted using the SWISSADME computational tool. Results: A total of eight (8) bioactive compounds were initially obtained from Chlorella sorokiniana through the GCMS analysis. Based on their docking scores, five metabolites demonstrated higher binding affinities compared to Isoniazid, namely 1H-pyrrole-2,5-dione, 1(4-chlorophenyl); 6-octadecenoic acid, (Z)-; and 9,15-octadecadienoic acid, methyl ester (Z,Z)-. These compounds exhibited notable antibacterial potential, with molecular docking analysis revealing strong interactions with the sulfur ester dioxygenase enzyme (4CVY). The ADMET predictions further supported the drug-likeness and pharmacological potential of these metabolites obtained using computational tools SWISSADME. Conclusion: The findings of this study revealed Chlorella sorokiniana as a promising natural source of bioactive metabolites with potential therapeutic activity against MDR-TB sulphur ester dioxygenase 4CVY.