Discovery of Novel Antimicrobial Lead Compounds and Innovative Strategies Based on Natural Products

Natural products (NPs) have been an important source of drug discovery and development due to their novel structures and wide range of pharmacological activities. Especially in the discovery of antibiotics, most antibiotics are derived from NPs and their derivatives, such as penicillin G, amoxicillin, oxytetracycline, and minocycline. NPs have particular advantages over purely synthetic molecules. They are evolutionarily optimized structurally for specific biological functions, including anti-infective activity, interaction with other organisms, and receptor/protein binding. In addition, NPs have a broader chemical space than typical synthetic small molecule compound libraries, bringing the advantages of scaffold diversity and structural novelty. Due to the large number of sp3 carbon atoms and chiral centers, NPs have the unique ability to interact with receptors and demonstrate targeting selectivity. Therefore, NP-based antimicrobial drug discovery is one of the hot topics in current research.

This Research Topic aims to collate cutting-edge research advances regarding NPs and their analogues as antimicrobial agents, to infuse renewed vigor into this vital field. This solicitation mainly focuses on four aspects: (1) the discovery and characterization of antimicrobial NPs featuring novel chemotypes and unique mechanisms of action; (2) investigation into the strategies NPs employ to counteract bacterial resistance, including their role as resistance-modifying or anti-virulence agents, and their synergistic effects with existing antibiotics; (3) the rational optimization and structural modification of promising NP scaffolds for the development of high-efficacy lead compounds with improved drug-like properties; and (4) the innovative development of NP-based antimicrobial materials (e.g., coatings, implants) and intelligent, targeted delivery systems to enhance therapeutic efficacy.

This Research Topic aims to showcase the latest advancements in harnessing NPs and their analogues to combat antibacterial resistance. We seek to bridge fundamental discovery with translational applications, highlighting the unique role of NPs in inspiring next-generation anti-infective strategies. Specific themes of interest include:
- Discovery of novel NPs with unique chemotypes and mechanisms of action.
- Investigation of NPs as resistance-modifying, anti-virulence, or synergistic agents.
- Optimization of NP scaffolds for high-efficacy lead compound development.
- Development of innovative NP-based antimicrobial materials and smart delivery systems.
We welcome the submission of Original Research, Review, and Mini-Review articles that address these challenges and contribute to revitalizing the antibiotic pipeline.

Keywords: Natural products, structure optimization, antibiotic discovery, antimicrobial discovery, resistance, novel agents, delivery systems

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.