In Silico Based Identification Of Novel Inhibitors For Selected MDR Protein From Shigella Species: A Validation Through Molecular Docking Analysis

Abstract

Gram-negative Enterobacteriaceae pathogenic strains of Shigella organisms cause bacillary dysentery and shigellosis. Three serogroups-Shigella dysenteriae, flexneri, boydii, and sonnei and one serotype-Sonnei, are groups A, B, C, and D, respectively. Shigella flexneri is the most common serogroup worldwide. Fecal-oral transmission is the main method, but sexual transmission has been recorded. These groups are among the most responsible for diarrheal diseases. In children, this species can lead to stunted growth due to severe and life-threatening illnesses. In the present day situation, managing this infection is still challenging as it can easily resist many antimicrobials, and overcoming this and finding potential inhibitors can help reduce this infection. As a result, this research aims to determine the potential inhibitors against the potential protein target through molecular docking analysis. According to the virulence factor, subcellular localisation, and role in infection, the aminoglycoside'-(9)O-adenyltransferase protein was the most potent target protein. The three-dimensional structure was designed and validated, it became known that designed model has a promising profile according to the Ramachandran plot analysis. Further, the molecular docking analysis targeted available ligands in ZINC databases and found 10 potential novel inhibitors. Among these, only 6 inhibitors were found to have the most potential as per toxicity analysis. These findings suggested that these selected inhibitors can be utilised to combat this infection; however, further experimental validation is required to confirm their efficacy.