Virus Meets Chemistry: Chemical, Genomic, and Structural Strategies for Targeted Bacteriophage Therapeutics

Objectives: To explore the molecular chemistry and structural biology of bacteriophages as precision-guided therapeutic agents. This review reframes phages as programmable nanomachines governed by defined chemical interactions, focusing on their relevance to antimicrobial resistance, targeted lysis, and synthetic modification.Materials and Methods: A systematic review was conducted using recent peer-reviewed literature from PubMed, Scopus, and Google Scholar, covering bacteriophage structural biology, enzymatic lysis mechanisms, chemical modifications, genomic annotation, and bioengineering techniques. Studies were selected based on relevance to molecular chemistry, nanotechnology, and therapeutic development.Results: Bacteriophages demonstrate ligand-specific host recognition, capsid-mediated genome packaging, and enzymatic lysis using holins and endolysins. Advances in PEGylation, surface conjugation, and CRISPR engineering have expanded their therapeutic potential. Genomic tools now enable personalized phage matching, while hybrid phage-nanoparticle systems enhance targeting and delivery.Conclusions: Phages can be rationally designed as chemically programmable antimicrobials. Their structure–function relationship, enzymatic precision, and genomic adaptability position them as promising agents in the fight against multidrug-resistant pathogens. Integration of chemistry, bioinformatics, and synthetic biology enables development of next-generation phage therapeutics.