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Updated: Jan 18, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Recent advances in protein synthesis inhibitors
Alisa P Chernyshova1, Petr V Sergiev2, Dmitrii A Lukianov3
1Center for Molecular and Cellular Biology, Moscow, 121205 Skolkovo, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, Moscow 117997, Russia; Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia.
Abstract:
Antimicrobial resistance threatens the long-standing efficacy of antibiotics and underscores the need to expand, refine, and diversify antimicrobial therapies. Translation is a uniquely druggable process: its machinery is essential, conserved in bacteria, and sufficiently divergent from the eukaryotic counterpart to enable selectivity. This review synthesizes recent progress on inhibitors of initiation, elongation, termination, and recycling. High-resolution structural and biophysical studies have resolved longstanding ambiguities, reassigned ribosomal binding sites, uncovered stage-specific activities in scaffolds previously thought to act elsewhere, and revealed multistage, context-dependent mechanisms. Beyond the canonical stages, quality-control pathways that offer orthogonal points of intervention were observed. Collectively, these advances support structure-guided, context-aware, and hybrid/combination strategies for antibiotic design and therapeutic development.
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