Genomic Analysis of Neisseria gonorrhoeae WHO_A_2024 and Molecular Docking and ADMET Evaluation of Quercetin against Penicillin-Binding Protein 2 (PBP2): An in Silico Study

Abstract

Even though Neisseria gonorrhoeae is still one of the most significant bacterial sexually transmitted infections (STIs), growing antimicrobial resistance (AMR) is a significant barrier to treatment and disease control. This study was designed to characterize the genomic profile and antimicrobial resistance of N. gonorrhoeae WHO_A_2024 and to assess the in silico interaction and ADMET properties of Quercetin with penicillin-binding protein 2 (PBP2). The complete genome sequence of the WHO_A_2024 genome (GCF_040404645.1) was used for multilocus sequence typing (MLST), identification of antimicrobial resistance genes, and CRISPR–Cas-associated sequences. Molecular docking was used to evaluate the binding between quercetin and PBP2 (PDB ID: 6P54), and then computational ADMET analysis was performed. The genome was a 2,308,468 bp chromosome having 52% GC content. Seven-locus matches were observed between ST10316 and WHO_A_2024 by MLST. The only determinant associated with a predicted resistant phenotype was for rpsE T24P substitution, is a low-level spectinomycin resistance. Extended-spectrum cephalosporins, fluoroquinolones, tetracyclines, and macrolides were not expected to show resistance. Four short and low-confidence CRISPR and one General-Class1 Cas-associated cluster were found. The hydrogen-bond, van der Waals, and π-mediated interactions resulted in a predicted PBP2 binding affinity of −6.707 kcal mol−1 for quercetin. The drug-likeness was moderate, and intestinal absorption was predicted by ADMET analysis, but some limitations in permeability and bioavailability and some metabolic and toxicity alerts were found. Integrated genomic and computational analyses identified WHO_A_2024 and suggested quercetin as a possible candidate for binding to PBP2. These computational findings need to be validated by experimental antimicrobial, pharmacokinetic, target-engagement, and safety studies.