همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Aureolysin Inhibition: Identification of Sigmoidin B as a Potential Therapeutic Candidate against Staphylococcus aureus

نویسندگان :

Amir Mohammad Akbarian Khujin¹ Melika Sadat Samadi² Ghazal Shirdel³ Elnaz Afshari⁴

1- Department of Microbiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran 2- Department of Microbiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran 3- Department of Microbiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran 4- 1 Department of Microbiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran. 2 Department of Microbiology and Microbial Biotechnology, Biological Science and Technology Branch, Shahid Beheshti University, Tehran, Iran.

کلمات کلیدی :

Staphylococcus aureus،Aureolysin،Sigmoidin B،Molecular Docking

چکیده :

Abstract Introduction Staphylococcus aureus is a highly adaptable pathogen responsible for various infections, from mild skin conditions to life-threatening diseases such as pneumonia, endocarditis, toxic shock syndrome, and sepsis (Gherardi, 2023). A crucial virulence factor in this bacterium is aureolysin, a metalloprotease that subverts host defenses by inhibiting neutrophils and compromising the body's immune response (Laarman et al., 2011). The growing concern of antibiotic-resistant S. aureus strains has sparked interest in developing novel antimicrobial strategies. One promising approach is to target aureolysin, as inhibiting this protein could significantly impair S. aureus colonization and proliferation. However, specific inhibitors of aureolysin have yet to be identified. To address this gap, our study utilized molecular docking to evaluate twenty potential inhibitory ligands and determine the most effective candidate. These findings provide a foundation for developing innovative antimicrobial therapies to combat S. aureus infections, a pressing need in the face of rising antibiotic resistance. Material and Methods The 3D structure of Aureolysin (PDB ID: 7skL) was obtained from the RCSB PDB database. Luteolin (PubChem CID: 5280445) and twenty of its analogs were selected as potential inhibitors from the PubChem database in SDF format. After preparing the protein and ligands, molecular docking was carried out using Virtual Docker Molegro version 6.0. The interactions were analyzed to identify the best binding with the lowest energy using Molegro Molecular Viewer software. Finally, the pharmacokinetic properties, including absorption, distribution, metabolism, and excretion, were evaluated using the SwissADME server. Results and Conclusion Among all the inhibitory analogs, luteolin, and its derivatives, the most effective analog for Aureolysin was identified as sigmoidin B. This compound has a molecular weight of 356.37 g/mol and a binding energy of -115.799 kcal/mol. Sigmoidin B formed three steric interactions with the Aureolysin residues His356, Trp325, and Asn364, along with four hydrogen bonds involving Gln360, Asn364, Asn375, and His356. However, no electrostatic bonds were observed between sigmoidin B and Aureolysin. The ADME analysis revealed that sigmoidin B has a logS (water solubility) score of -4.68, a lipophilicity (XLogP3) of 3.95, a polarity (TPSA) of 107.22, and four hydrogen bond donors and six hydrogen bond acceptors. These properties suggest that sigmoidin B is a promising candidate for inhibiting Aureolysin in Staphylococcus aureus. Further in vitro and in vivo studies are required to confirm its efficacy and potential as a therapeutic agent.