Makayla R. Hedges, Kevin P. C. Minbiole, Barry S. Selinsky, William M. Wuest
Disinfectants represent a crucial tool in killing infectious diseases and play a major role in protecting susceptible communities (hospitals and nursing homes). Inspired by nature, over the past 100 years, scientists have sought to recreate simplified antimicrobial peptides (AMPs) to serve these purposes. Quaternary ammonium compounds (QACs) have been mainstays in the industry, with benzalkonium chloride and didecyldimethylammonium chloride representing everyday disinfection agents. Through exhaustive investigations into alternative QAC structures, we have observed a "floor" in activity, with minimum inhibitory concentration (MIC) values of approximately 0.5 μM and no lower. Interestingly, the same value arises when one calculates the theoretical maximum in activity when considering the mechanism of action, aligning with the previously reported maximum inhibitory efficacy of AMPs. Herein, we encourage that the future development of novel disinfectants instead focus on five specific design elements: cost, time-kill, toxicity, sustainability, and resistance susceptibility.