ABSTRACT
Quaternary ammonium compounds have served as a first line of protection for human health as surface disinfectants and sanitizers for nearly a century. However, increasing levels of bacterial resistance have spurred the development of novel QAC architectures. In light of the observed reduction in eukaryotic cell toxicity when the alkyl chains on QACs are shorter in nature (≤10â C), we prepared 47 QAC architectures that bear multiple short alkyl chains appended to up to three cationic groups, thus rendering them "bushy-tailed" multiQACs. Antibacterial activity was strong (often ~1-4â µM) in a varied set of bushy-tailed architectures, though observed therapeutic indices were not significantly improved over QAC structures bearing fewer and longer alkyl chains.
ABSTRACT
Quaternary ammonium compound (QAC) disinfectants represent one of our first lines of defense against pathogens. Their inhibitory and bactericidal activities are usually tested through minimum inhibitory concentration (MIC) and time-kill assays, but these assays can become cumbersome when screening many compounds. We investigated how the dynamic surface tension (DST) measurements of QACs correlate with these antimicrobial activities by testing a panel of potent and structurally varied QACs against the gram-positive Staphylococcus aureus and the gram-negative Pseudomonas aeruginosa. We found that DST values correlated well with bactericidal activity in real-world disinfection conditions but not with MIC values. Moreover, no correlation between these two antimicrobial activities of QACs (bactericidal and inhibition) was observed. In addition, we observed that the bactericidal activity of our QAC panel against the gram-negative P. aeruginosa was severely affected in the presence of hard water. Interestingly, we found that the counterion of the QAC affects the killing of bacteria in these conditions, a phenomenon not observed in most MIC assessments. Moreover, some of our best-in-class QACs show enhanced bactericidal activity when combined with a commercially available QAC. In conclusion, we determined that an intrinsic physical property of QACs (DST) can be used as a technique to screen for bactericidal activity of QACs in conditions that mimic real-world disinfection conditions.
ABSTRACT
Cationic biocides play a crucial role in the disinfection of domestic and healthcare surfaces. Due to the rise of bacterial resistance towards common cationic disinfectants like quaternary ammonium compounds (QACs), the development of novel actives is necessary for effective infection prevention and control. Toward this end, a series of 15 chimeric biscationic amphiphilic compounds, bearing both ammonium and phosphonium residues, were prepared to probe the structure and efficacy of mixed cationic ammonium-phosphonium structures. Compounds were obtained in two steps and good yields, with straightforward and chromatography-free purifications. Antibacterial activity evaluation of these compounds against a panel of seven bacterial strains, including two MRSA strains as well as opportunistic pathogen A. baumannii, were encouraging, as low micromolar inhibitory activity was observed for multiple structures. Alkyl chain length on the ammonium group was, as expected, a major determinant of bioactivity. In addition, high therapeutic indexes (up to 125-fold) for triphenyl phosphonium-bearing amphiphiles were observed when comparing antimicrobial activity to mammalian cell lysis activity.
Subject(s)
Anti-Bacterial Agents , Disinfectants , Microbial Sensitivity Tests , Organophosphorus Compounds , Quaternary Ammonium Compounds , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Quaternary Ammonium Compounds/chemical synthesis , Disinfectants/pharmacology , Disinfectants/chemistry , Disinfectants/chemical synthesis , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacology , Organophosphorus Compounds/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Surface-Active Agents/chemistry , Surface-Active Agents/pharmacology , Surface-Active Agents/chemical synthesis , Humans , Acinetobacter baumannii/drug effects , Dose-Response Relationship, DrugABSTRACT
Quaternary ammonium compounds (QACs) serve as a first line of defense against infectious pathogens. As resistance to QACs emerges in the environment, the development of next-generation disinfectants is of utmost priority for human health. Balancing antibacterial potency with environmental considerations is required to effectively counter the development of bacterial resistance. To address this challenge, a series of 14 novel biscationic quaternary phosphonium compounds (bisQPCs) have been prepared as amphiphilic disinfectants through straightforward, high-yielding alkylation reactions. These compounds feature decomposable or "soft" amide moieties in their side chains, anticipated to promote decomposition under environmental conditions. Strong bioactivity against a panel of seven bacterial pathogens was observed, highlighted by single-digit micromolar activity for compounds P6P-12A,12A and P3P-12A,12A. Hydrolysis experiments in pure water and in buffers of varying pH revealed surprising decomposition of the soft QPCs under basic conditions at the phosphonium center, leading to inactive phosphine oxide products; QPC stability (>24 h) was maintained in neutral solutions. The results of this work unveil soft QPCs as a potent and environmentally conscious new class of bisQPC disinfectants.
Subject(s)
Anti-Infective Agents , Disinfectants , Humans , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Quaternary Ammonium Compounds/pharmacology , Quaternary Ammonium Compounds/chemistry , Anti-Bacterial Agents/pharmacology , BacteriaABSTRACT
Eastern hellbenders Cryptobranchus alleganiensis alleganiensis, large aquatic salamanders, are declining over most of their range. The amphibian-killing fungus Batrachochytrium dendrobatidis (Bd) has contributed to global amphibian declines and has been detected on eastern hellbenders, but infection intensities were lower than those of species that are more susceptible to Bd. The factors limiting Bd on hellbenders may include antifungal metabolites produced by their skin microbiota. We used a metabolite fingerprinting technique to noninvasively identify the presence, but not identity, of metabolites associated with eastern hellbenders. We surveyed the skin of wild eastern hellbenders to test whether the composition and richness (i.e. number of metabolites) of their metabolites are explained by Bd status or location. Furthermore, we surveyed for metabolites on captive eastern hellbenders to test whether metabolite compositions were different between captive and wild eastern hellbenders. Bd detection was not associated with either metabolite richness or composition. Both metabolite composition and richness differed significantly on hellbenders from different locations (i.e. states). For metabolite composition, there was a statistical interaction between location and Bd status. Metabolite richness was greater on captive eastern hellbenders compared to wild hellbenders, and metabolite compositions differed between wild and captive eastern hellbenders. The methods we employed to detect metabolite profiles effectively grouped individuals by location even though metabolite composition and richness have high levels of intraspecific variation. Understanding the drivers and functional consequences of assemblages of skin metabolites on amphibian health will be an important step toward understanding the mechanisms that result in disease vulnerability.
Subject(s)
Chytridiomycota , Urodela , Animals , Urodela/microbiology , Amphibians , Batrachochytrium , Skin/microbiologyABSTRACT
Quaternary ammonium compounds (QACs) are vital disinfectants for the neutralization of pathogenic bacteria in clinical, domestic, and commercial settings. After decades of dependence on QACs, the emergence of antimicrobial resistance to this class of compounds threatens the ability of existing QAC products to effectively manage rising bacterial threats. The need for new disinfectants is therefore urgent, with quaternary phosphonium compounds (QPCs) emerging as a new class of promising antimicrobials that boast significant activity against highly resistant bacteria. Reported here is a series of twenty-one novel QPCs that replace phenyl substituents on the phosphorus center with alkyl groups yet allow for rapid synthetic routes in high yields. Within this series are structures containing methyl, ethyl, or cyclohexyl phosphonium substituents on bisphosphane scaffolds bearing ethyl linkers, affording atom economical structures and ones that represent exact analogs to nitrogenous amphiphiles. The resultant bisQPC structures display high antibacterial efficacy enjoyed by comparably constructed QACs, with three structures in the single-digit micromolar activity range despite structural simplification.
Subject(s)
Anti-Infective Agents , Disinfectants , Disinfectants/pharmacology , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Quaternary Ammonium Compounds/pharmacology , Quaternary Ammonium Compounds/chemistry , BacteriaABSTRACT
Over the past decades, the shortcomings of established quaternary ammonium disinfectants have become increasingly clear. Although benzalkonium chloride (BAC) has enjoyed nearly a century of significantly protecting human health through surgical preparation, home use, and industrial applications, increasing levels of bacterial resistance have rendered it decreasingly effective. In light of more recent efforts that have informed us that multicationic amphiphilic disinfectants show both higher activity as well as diminished susceptibility to resistance, we embarked on the preparation of 27â multicationic QACs in an attempt to clearly document structure-activity relationships of next-generation BAC structures. Select biscationic BAC derivatives demonstrate single-digit micromolar activity against all seven bacteria tested and MIC values of 2- to 32-fold better than BAC. Particularly notable is the improvement against the more concerning bacteria like Acinetobacter baumannii and Pseudomonas aeruginosa, which pose a modern threat to legacy disinfectants like BAC. With simple synthetic paths, consistently high yields (averaging â¼80 %), and strong biological activity, potent structures with clear SAR trends and strong therapeutic indices have been established.
Subject(s)
Benzalkonium Compounds , Disinfectants , Humans , Benzalkonium Compounds/pharmacology , Disinfectants/pharmacology , Bacteria , Microbial Sensitivity TestsABSTRACT
Acinetobacter baumannii is classified as a highest threat pathogen, urgently necessitating novel antimicrobials that evade resistance to combat its spread. Quaternary ammonium compounds (QACs) have afforded a valuable first line of defense against antimicrobial resistant pathogens as broad-spectrum amphiphilic disinfectant molecules. However, a paucity of innovation in this space has driven the emergence of QAC resistance. Through this work, we sought to identify next-generation disinfectant molecules with efficacy against highly resistant A. baumannii clinical isolates. We selected 12 best-in-class molecules from our previous investigations of quaternary ammonium and quaternary phosphonium compounds (QPCs) to test against a panel of 35 resistant A. baumannii clinical isolates. The results highlighted the efficacy of our next-generation compounds over leading commercial QACs, with our best-in-class QAC (2Pyr-11,11) and QPC (P6P-10,10) displaying improved activities with a few exceptions. Furthermore, we elucidated a correlation between colistin resistance and QAC resistance, wherein the only pan-resistant isolate of the panel, also harboring colistin resistance, exhibited resistance to all tested QACs. Notably, P6P-10,10 maintained efficacy against this strain with an IC90 of 3 µM. In addition, P6P-10,10 displayed minimum biofilm eradication concentrations as low as 32 µM against extensively drug resistant clinical isolates. Lastly, examining the development of disinfectant resistance and cross-resistance, we generated QAC-resistant A. baumannii mutants and observed the development of QAC cross-resistance. In contrast, neither disinfectant resistance nor cross-resistance was observed in A. baumannii under P6P-10,10 treatment. Taken together, the results of this work illustrate the need for novel disinfectant compounds to treat resistant pathogens, such as A. baumannii, and underscore the promise of QPCs, such as P6P-10,10, as viable next-generation disinfectant molecules.
Subject(s)
Acinetobacter baumannii , Disinfectants , Disinfectants/pharmacology , Drug Resistance, Bacterial , Colistin/pharmacology , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Quaternary Ammonium Compounds/pharmacologyABSTRACT
Biscationic quaternary phosphonium compounds (bisQPCs) represent a promising class of antimicrobials, displaying potent activity against both Gram-negative and Gram-positive bacteria. In this study, we explored the effects of structural rigidity on the antimicrobial activity of QPC structures bearing a two-carbon linker between phosphonium groups, testing against a panel of six bacteria, including multiple strains harboring known disinfectant resistance mechanisms. Using simple alkylation reactions, 21 novel compounds were prepared, although alkene isomerization as well as an alkyne reduction were observed during the respective syntheses. The resulting bisQPC compounds showed strong biological activity, but were hampered by diminished solubility of their iodide salts. One compound (P2P-10,10 I) showed single-digit micromolar activity against the entire panel of bacteria. Overall, intriguing biological activity was observed, with less rigid structures displaying better efficacy against Gram-negative strains and more rigid structures demonstrating slightly increased efficacy against S. aureus strains.
Subject(s)
Anti-Infective Agents , Staphylococcus aureus , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Bacteria , Gram-Negative Bacteria , Gram-Positive Bacteria , Microbial Sensitivity TestsABSTRACT
Variation in the structure of host-associated microbial communities has been correlated with the occurrence and severity of disease in diverse host taxa, suggesting a key role of the microbiome in pathogen defense. However, whether these correlations are typically a cause or consequence of pathogen exposure remains an open question, and requires experimental approaches to disentangle. In amphibians, infection by the fungal pathogen Batrachochytrium dendrobatidis (Bd) alters the skin microbial community in some host species, whereas in other species, the skin microbial community appears to mediate infection dynamics. In this study, we completed experimental Bd exposures in three species of tropical frogs (Agalychnis callidryas, Dendropsophus ebraccatus,andCraugastor fitzingeri) that were sympatric with Bd at the time of the study. For all three species, we identified key taxa within the skin bacterial communities that were linked to Bd infection dynamics. We also measured higher Bd infection intensities in D. ebraccatus and C. fitzingeri that were associated with higher mortality in C. fitzingeri. Our findings indicate that microbially mediated pathogen resistance is a complex trait that can vary within and across host species, and suggest that symbiont communities that have experienced prior selection for defensive microbes may be less likely to be disturbed by pathogen exposure.
Subject(s)
Chytridiomycota , Microbiota , Amphibians/microbiology , Animals , Bacteria/genetics , Disease Resistance , Skin/microbiologyABSTRACT
Amphibian populations have been declining around the world for more than five decades, and the losses continue. Although causes are complex, major contributors to these declines are two chytrid fungi, Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans, which both cause the disease termed chytridiomycosis. Previously, we showed that B. dendrobatidis impedes amphibian defenses by directly inhibiting lymphocytes in vitro and in vivo by release of soluble metabolites, including kynurenine (KYN), methylthioadenosine (MTA), and spermidine (SPD). Here, we show that B. salamandrivorans cells and cell-free supernatants also inhibit amphibian lymphocytes as well as a human T cell line. As we have shown for B. dendrobatidis, high-performance liquid chromatography (HPLC) and mass spectrometry revealed that KYN, MTA, and SPD are key metabolites found in the B. salamandrivorans supernatants. Production of inhibitory factors by B. salamandrivorans is limited to mature zoosporangia and can occur over a range of temperatures between 16°C and 26°C. Taken together, these results suggest that both pathogenic Batrachochytrium fungi have evolved similar mechanisms to inhibit lymphocytes in order to evade clearance by the amphibian immune system.
Subject(s)
Chytridiomycota , Animals , Humans , Amphibians , Batrachochytrium , Kynurenine/metabolism , Lymphocytes , Spermidine/metabolism , UrodelaABSTRACT
Quaternary ammonium compounds (QACs) serve as mainstays in the formulation of disinfectants and antiseptics. However, an over-reliance and misuse of our limited QAC arsenal has driven the development and spread of resistance to these compounds, as well as co-resistance to common antibiotics. Extensive use of these compounds throughout the COVID-19 pandemic thus raises concern for the accelerated proliferation of antimicrobial resistance and demands for next-generation antimicrobials with divergent architectures that may evade resistance. To this end, we endeavored to expand beyond canonical ammonium scaffolds and examine quaternary phosphonium compounds (QPCs). Accordingly, a synthetic and biological investigation into a library of novel QPCs unveiled biscationic QPCs to be effective antimicrobial scaffolds with improved broad-spectrum activities compared to commercial QACs. Notably, a subset of these compounds was found to be less effective against a known QAC-resistant strain of MRSA. Bioinformatic analysis revealed the unique presence of a family of small multiresistant transporter proteins, hypothesized to enable efflux-mediated resistance to QACs and QPCs. Further investigation of this resistance mechanism through efflux-pump inhibition and membrane depolarization assays illustrated the superior ability of P6P-10,10 to perturb the cell membrane and exert the observed broad-spectrum potency compared to its commercial counterparts. Collectively, this work highlights the promise of biscationic phosphonium compounds as next-generation disinfectant molecules with potent bioactivities, thereby laying the foundation for future studies into the synthesis and biological investigation of this nascent antimicrobial class.
Subject(s)
COVID-19 , Disinfectants , Disinfectants/pharmacology , Drug Resistance, Bacterial , Humans , Microbial Sensitivity Tests , Pandemics , SARS-CoV-2ABSTRACT
Apocynaceae are well known for diverse specialized metabolites that are distributed in a phylogenetically informative manner. Pyrrolizidine alkaloids (PAs) have been reported sporadically in one lineage in the family, the APSA clade, but few species have been studied to date. We conducted the first systematic survey of Apocynaceae for retronecine-type PAs, sampling leaves from 231 species from 13 of 16 major lineages within the APSA clade using HPLC-MS/MS. We also followed up preliminary evidence for infra-specific variation of PA detectability in Echites umbellatus Jacq. Four precursor ion scans (PREC) were developed for a high-throughput survey for chemicals containing a structural moiety common to many PAs, the retronecine core. We identified with high confidence PAs in 7 of 8 sampled genera of tribe Echiteae, but not in samples from the closely related Odontadenieae and Mesechiteae, confirming the utility of PAs as a taxonomic character in tribal delimitation. Occurrence of PAs in Malouetieae is reported with moderate confidence in Galactophora schomburgkiana Woodson and Eucorymbia alba Stapf, but currently we have low confidence of their presence in Holarrena pubescens Wall. ex G. Don (the one Malouetieae species where they were previously reported), as well as in Holarrena curtisii King & Gamble and in Kibatalia macrophylla (Pierre ex Hua) Woodson. Candidate PAs in some species of Wrightia R. Br. (Wrightieae) and Marsdenia R. Br. (Marsdenieae) are proposed with moderate confidence, but a subset of the compounds in these taxa presenting with a PA-like fragmentation pattern are more likely to be aminobenzoyl glycosides. Candidate PAs are reported in species with predicted (VXXXD) and unexpected (IXXXN) amino acid motifs in their homospermidine synthase-like genes. Detectability of PAs varies among samples of Echites umbellatus and intra-individual plasticity contributes to this variation. Of toxicological importance, novel potential sources of human exposure to pro-toxic PAs were identified in the medicinal plant, Wrightia tinctoria R.Br., and the food plants, Marsdenia glabra Cost. and Echites panduratus A. DC., warranting immediate further research to elucidate the structures of the candidate PAs identified. Method development and limitations are discussed.
Subject(s)
Apocynaceae , Pyrrolizidine Alkaloids , Chromatography, High Pressure Liquid , Tandem Mass SpectrometryABSTRACT
A two-step metal-halogen exchange and diastereoselective copper-mediated Michael addition onto a complex α,ß-unsaturated system has been developed and applied toward the synthesis of bisaryl Nrf2 activators. Optimization of metal-halogen exchange using (n-Bu)3MgLi allowed for the preparation of custom aryl-functionalized magnesiate reagents at noncryogenic temperatures. Following transmetalation, these reagents were used in highly diastereoselective Michael addition reactions.
ABSTRACT
Recent advances in the development of quaternary ammonium compounds (QACs) have focused on new structural motifs to increase bioactivity, but significantly less studied has been the change from ammonium- to sulfonium-based disinfectants. Herein, we report the synthesis of structurally analogous series of quaternary ammonium and trivalent sulfonium compounds (TSCs). The bioactivity profiles of these compounds generally mirror each other, and the antibacterial activity of sulfonium-based THT-18 was found to be comparable to the commercial disinfectant, BAC. The development of these compounds presents a new avenue for further study of disinfectants to combat the growing threat of bacterial resistance.
Subject(s)
Bacteria/drug effects , Quaternary Ammonium Compounds/pharmacology , Sulfonium Compounds/pharmacology , Surface-Active Agents/pharmacology , Thiophenes/pharmacology , Dose-Response Relationship, Drug , Erythrocytes/drug effects , Erythrocytes/metabolism , Humans , Microbial Sensitivity Tests , Molecular Structure , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Structure-Activity Relationship , Sulfonium Compounds/chemical synthesis , Sulfonium Compounds/chemistry , Surface-Active Agents/chemical synthesis , Surface-Active Agents/chemistry , Thiophenes/chemical synthesis , Thiophenes/chemistryABSTRACT
Inspired by the incorporation of metallocene functionalities into a variety of bioactive structures, particularly antimicrobial peptides, we endeavored to broaden the structural variety of quaternary ammonium compounds (QACs) by the incorporation of the ferrocene moiety. Accordingly, 23 ferrocene-containing mono- and bisQACs were prepared in high yields and tested for activity against a variety of bacteria, including Gram-negative strains and a panel of clinically isolated MRSA strains. Ferrocene QACs were shown to be effective antiseptics with some displaying single-digit micromolar activity against all bacteria tested, demonstrating yet another step in the expansion of structural variety of antiseptic QACs.
Subject(s)
Anti-Bacterial Agents/pharmacology , Ferrous Compounds/pharmacology , Metallocenes/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Quaternary Ammonium Compounds/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Dose-Response Relationship, Drug , Ferrous Compounds/chemistry , Metallocenes/chemistry , Microbial Sensitivity Tests , Molecular Structure , Quaternary Ammonium Compounds/chemistry , Structure-Activity RelationshipABSTRACT
Amphibians host diverse skin bacteria that have a role in pathogen defense, but these skin communities could change over time and impact this function. Here, we monitored individual Eastern red-spotted newts (Notophthalmus viridescens; N = 17) for 2 years in a field pond enclosure and assessed the effects of season and disturbance on skin bacterial community dynamics. We created disturbances by adding additional pond substrate to the enclosure at two timepoints. We planned to sample the skin bacterial community and metabolite profiles of each newt every 6 weeks; we ultimately sampled eight individuals at least six times. We used 16S rRNA gene amplicon sequencing to characterize the bacterial communities and HPLC-MS for metabolite profiling. We found that disturbance had a dramatic effect on skin bacterial communities and metabolite profiles, while season had an effect only using select metrics. There were seven core bacterial taxa (97% OTUs) that were found on all newts in all seasons, pre- and post-disturbance. Lastly, there was a correlation between bacterial and metabolite profiles post-disturbance, which was not observed pre-disturbance. This longitudinal study suggests that environmental disturbances can have lasting effects on skin bacterial communities that overwhelm seasonal changes, although the core bacteria remain relatively consistent over time.
Subject(s)
Amphibians , Bacteria , Animals , Bacteria/genetics , Ecosystem , Humans , Longitudinal Studies , RNA, Ribosomal, 16S/genetics , Seasons , SkinABSTRACT
The prevalence of quaternary ammonium compounds (QACs) as common disinfecting agents for the past century has led bacteria to develop resistance to such compounds. Given the alarming increase in resistant strains, new strategies are required to combat this rise in resistance. Recent efforts to probe and combat bacterial resistance have focused on studies of multiQACs. Relatively unexplored, however, have been changes to the primary atom bearing positive charge in these antiseptics. Here we review the current state of the field of both phosphonium and sulfonium amphiphilic antiseptics, both of which hold promise as novel means to address bacterial resistance.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Infective Agents, Local/pharmacology , Bacteria/drug effects , Drug Resistance, Bacterial/drug effects , Quaternary Ammonium Compounds/pharmacology , Surface-Active Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Infective Agents, Local/chemical synthesis , Anti-Infective Agents, Local/chemistry , Drug Development , Microbial Sensitivity Tests , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Surface-Active Agents/chemical synthesis , Surface-Active Agents/chemistryABSTRACT
A novel virus named Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) emerged from Wuhan, China in late 2019. Since then, the virus has quickly spread worldwide, leading the World Health Organization to declare it as a pandemic; by the end of April 2020, the number of cases exceeded 3 million. Due to the high infectivity rate, SARS-CoV-2 is difficult to contain, making disinfectant protocols vital, especially for essential, highly trafficked areas such as hospitals, grocery stores, and delivery centers. According to the Centers for Disease Control and Prevention, best practices to slow the spread rely on good hand hygiene, including proper handwashing practices as well as the use of alcohol-based hand sanitizers. However, they provide warning against sanitizing products containing benzalkonium chloride (BAC), which has sparked concern in both the scientific community as well as the general public as BAC, a common quaternary ammonium compound (QAC), is ubiquitous in soaps and cleaning wipes as well as hospital sanitation kits. This viewpoint aims to highlight the outdated and incongruous data in the evaluation of BAC against the family of known coronaviruses and points to the need for further evaluation of the efficacy of QACs against coronaviruses.