Discovery of Novel Antimicrobial Agents and Innovative Strategies Based on Natural Products, Volume II

Natural products (NPs) have long been a foundational source of anti-infective agents. Most clinically used antibiotics derive from NPs or, more commonly, from semisynthetic derivatives obtained by chemical modification of natural scaffolds. Penicillin G is a naturally occurring β-lactam, whereas amoxicillin and minocycline are semisynthetic derivatives. Although NPs are often described as evolutionarily pre-optimized for biological function and as occupying a broader, stereochemically richer chemical space than conventional synthetic libraries, this advantage is debated rather than settled. NP-based discovery is constrained by high rediscovery rates of known chemotypes, and many NPs exhibit poor drug-likeness, including high molecular weight, limited aqueous solubility, and metabolic instability. Contemporary NP antimicrobial research therefore increasingly centers on the rational derivatization of natural scaffolds and NP-inspired drug design to convert promising hits into drug-like leads with well-defined mechanisms of action. Accordingly, this Research Topic prioritizes studies on NP derivatives and NP-based drug design over the mere rediscovery of known chemotypes.This Research Topic focuses on the discovery, optimization, and design of natural product (NP) derivatives and NP-based antimicrobial agents against bacterial and fungal pathogens, with a strong emphasis on translational relevance and in vivo validation. The scope is deliberately limited to antibacterial and antifungal agents. Beyond therapeutic lead discovery, we also welcome applied studies that translate NP-derived antimicrobials into disinfectants, food preservatives, and antimicrobial coatings and materials.Specific themes of interest include:- Discovery and characterization of novel NP derivatives and NP-inspired leads with unique chemotypes and defined mechanisms of action against bacterial and fungal pathogens.- Evaluation of NPs and their derivatives as resistance-modifying agents, anti-virulence agents, or synergistic partners of established antibiotics and antifungals.- Medicinal-chemistry optimization and structure–activity relationship (SAR) studies of NP scaffolds to improve potency, selectivity, and drug-like properties for lead development.- Development of NP-based antimicrobial materials (coatings and implants), disinfectants, food preservatives, and smart targeted delivery systems.To ensure reproducibility and translational value, the expected standards of evidence differ by approach. Resistance-modifying agents (e.g., efflux-pump or β-lactamase inhibitors) should report target-specific inhibition assays together with potentiation of the partner antibiotic against resistant strains. Synergistic combinations should report fractional inhibitory concentration indices (FICI ≤ 0.5 indicating synergy), checkerboard or time–kill assays, and, where feasible, in vivo combination efficacy. Anti-virulence agents should demonstrate inhibition of the relevant virulence determinant (e.g., biofilm formation, toxin production, quorum sensing) and reduced pathogenesis in a relevant host model, rather than direct growth inhibition alone. Studies reporting therapeutic antimicrobial leads should include in vivo efficacy data (e.g., murine infection models) with appropriate controls. For non-therapeutic applications (disinfectants, food preservatives, coatings), application-relevant validation is required.We welcome the submission of Original Research, Review, and Mini-Review articles within the antibacterial and antifungal scope described above. Pure in silico or in vitro hit identification without mechanism-of-action or activity validation is outside the scope of this Topic. Topic editors: Yong Guo, Qingbin Cui, Jiangkun Dai, Weiguo Feng Source: https://www.frontiersin.org/research-topics/87206/discovery-of-novel-antimicrobial-agents-and-innovative-strategies-based-on-natural-products-volume-ii