Background:Community-acquired bacterial pneumonia(CABP)poses a serious public health threat,particularly with the emergence of drug-resistant bacterial strains.This study aims to investigate the molecular interactions...Background:Community-acquired bacterial pneumonia(CABP)poses a serious public health threat,particularly with the emergence of drug-resistant bacterial strains.This study aims to investigate the molecular interactions of Nafithromycin(Miqnaf®),India’s first indigenous next-generation macrolide antibiotic,and evaluate its potential against Streptococcus pneumoniae,a key pathogen responsible for CABP.Targeting 23S rRNA is critical for overcoming antibiotic resistance since it is involved in bacterial protein production.Many antibiotics,including macrolides target this rRNA.Mutations in 23S rRNA frequently result in resistance;therefore,designing medicines that bind new or conserved areas of 23S rRNA can circumvent current resistance mechanisms and restore antibiotic potency.Nafithromycin has excellent therapeutic potential,with a short three-day regimen and much higher efficacy than conventional macrolides.Its high lung tissue penetration and robust effectiveness against drug-resistant respiratory bacteria make it a promising next-generation antibiotic.Methods:To elucidate the interaction of Nafithromycin with bacterial ribosomal RNA,molecular docking studies were performed using AutoDock Vina.The three-dimensional structure of Streptococcus pneumoniae 23S rRNA was retrieved from the Protein Data Bank(PDB).The ligand structure of Nafithromycin was obtained from the PubChem database and prepared using Open Babel.Docking simulations targeted key functional regions-Domains II and V of 23S rRNA-known to be critical for bacterial protein synthesis.Binding affinities were calculated,and molecular interactions such as hydrogen bonds,hydrophobic contacts,and conformational stabilities were analyzed using Discovery Studio and PyMOL.Results:Nafithromycin exhibited a high binding affinity of-10.3 kcal/mol toward S.pneumoniae 23S rRNA.The compound formed stable interactions with both Domain II and Domain V,crucial regions involved in the inhibition of bacterial protein synthesis.Hydrogen bonding and hydrophobic interactions further stabilized the ligand-receptor complex.Compared to azithromycin,Nafithromycin demonstrated superior binding efficacy and a greater potential to inhibit resistant bacterial strains,indicating its structural advantages and enhanced ribosomal targeting.Conclusion:Nafithromycin demonstrates significant potential as a potent therapeutic agent against drug-resistant CABP.Its strong binding affinity,stable interactions with bacterial rRNA,favorable pharmacokinetic profile,and reduced resistance risk support its clinical utility and suggest its advantage over traditional macrolide antibiotics such as azithromycin.展开更多
文摘Background:Community-acquired bacterial pneumonia(CABP)poses a serious public health threat,particularly with the emergence of drug-resistant bacterial strains.This study aims to investigate the molecular interactions of Nafithromycin(Miqnaf®),India’s first indigenous next-generation macrolide antibiotic,and evaluate its potential against Streptococcus pneumoniae,a key pathogen responsible for CABP.Targeting 23S rRNA is critical for overcoming antibiotic resistance since it is involved in bacterial protein production.Many antibiotics,including macrolides target this rRNA.Mutations in 23S rRNA frequently result in resistance;therefore,designing medicines that bind new or conserved areas of 23S rRNA can circumvent current resistance mechanisms and restore antibiotic potency.Nafithromycin has excellent therapeutic potential,with a short three-day regimen and much higher efficacy than conventional macrolides.Its high lung tissue penetration and robust effectiveness against drug-resistant respiratory bacteria make it a promising next-generation antibiotic.Methods:To elucidate the interaction of Nafithromycin with bacterial ribosomal RNA,molecular docking studies were performed using AutoDock Vina.The three-dimensional structure of Streptococcus pneumoniae 23S rRNA was retrieved from the Protein Data Bank(PDB).The ligand structure of Nafithromycin was obtained from the PubChem database and prepared using Open Babel.Docking simulations targeted key functional regions-Domains II and V of 23S rRNA-known to be critical for bacterial protein synthesis.Binding affinities were calculated,and molecular interactions such as hydrogen bonds,hydrophobic contacts,and conformational stabilities were analyzed using Discovery Studio and PyMOL.Results:Nafithromycin exhibited a high binding affinity of-10.3 kcal/mol toward S.pneumoniae 23S rRNA.The compound formed stable interactions with both Domain II and Domain V,crucial regions involved in the inhibition of bacterial protein synthesis.Hydrogen bonding and hydrophobic interactions further stabilized the ligand-receptor complex.Compared to azithromycin,Nafithromycin demonstrated superior binding efficacy and a greater potential to inhibit resistant bacterial strains,indicating its structural advantages and enhanced ribosomal targeting.Conclusion:Nafithromycin demonstrates significant potential as a potent therapeutic agent against drug-resistant CABP.Its strong binding affinity,stable interactions with bacterial rRNA,favorable pharmacokinetic profile,and reduced resistance risk support its clinical utility and suggest its advantage over traditional macrolide antibiotics such as azithromycin.
