همایش ملی بیوانفورماتیک ایران

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

Investigation of Potent Inhibitors to Control Bacillus anthracis by Targeting Its Anthrax Toxin: A Molecular Docking Study

نویسندگان :

Melika Sadat Samadi¹ Ghazal Shirdel² Amir Mohammad Akbarian khujin³ 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 :

Bacillus anthracis،Molecular Docking،ADME

چکیده :

Introduction Bacillus anthracis is a Gram-positive, highly pathogenic, and zoonotic bacterium that has been a significant cause of morbidity and mortality throughout human history, with descriptions of the disease, characterized by severe pustular lesions, dating back to antiquity (CZEKAJ et al., 2024). Due to its potential for mass casualties and widespread harm, the Centers for Disease Control and Prevention (CDC) has designated Bacillus anthracis as a Category A agent, indicating its classification as a high-priority pathogen that poses a substantial risk to national security and public health (CZEKAJ et al., 2024). The anthrax toxin is a member of the AB toxin family, comprising a distinctive two-component structure. Specifically, it consists of a single B subunit, referred to as the protective antigen (PA), which facilitates the delivery of its toxic counterparts, and a pair of interchangeable A subunits, namely the edema factor (EF) and the lethal factor (LF). These A subunits exert distinct pathogenic effects, with EF causing edema and LF contributing to the toxin's lethal properties (Brossier and Mock, 2001). The increased occurrence of antibiotic-resistant strains and absence of effective treatments for anthrax underscore the importance of developing novel pharmacological methods for combating toxin-related illnesses. As the major virulence factor of anthrax is its toxin, our objective was to identify the most potent ligand for inhibiting the toxin as a potential drug candidate through molecular docking analysis. Methods The 3D structure of Bacillus anthracis toxin (PDB ID: 1J7N) was obtained from the RCSB PDB database. N-oleoyldopamine (CID 5282106) and thirty of its analogs were selected as 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. At the end, the pharmacokinetic properties were evaluated using the SwissADME server. Results and Discussion Among all the inhibitory ligands, the most effective analog for Bacillus anthracis toxin was identified as N-[2-(3,4-dihydroxyphenyl)ethyl]dodecanamide. This compound has a molecular weight of 195/22 g/mol and a binding energy of -150/229 kcal/mol. N-[2-(3,4-dihydroxyphenyl)ethyl]dodecanamide formed seven steric interactions with the toxin residues of Gln537(B), Tyr542(B), Pro492(B), Leu494(B), Ala493(A), Ala493(B), and Ser538(B), along with two hydrogen bonds with the toxin residues involving Ser538(A) and Pro492(B). However, no electrostatic bonds were observed between N-[2-(3,4-dihydroxyphenyl)ethyl]dodecanamide and Bacillus anthracis toxin. The ADME analysis revealed that N-[2-(3,4-dihydroxyphenyl)ethyl]dodecanamide has a logS (water solubility) score of -0.65, a lipophilicity (XLogP3) of -0.72, a polarity (TPSA) of 69.56Å², and three hydrogen bond donors and three hydrogen bond acceptors. These properties suggest that N-[2-(3,4-dihydroxyphenyl)ethyl]dodecanamide is a promising candidate for inhibiting Bacillus anthracis toxin. Further in vitro and in vivo studies are required to confirm it as a therapeutic agent