Hypochlorous Acid (HOCl) as a Promising Respiratory Antiseptic
Michael Winter, Dirk Boecker, Wilfried Posch
Viruses, doi:10.3390/v17091219
The COVID-19 pandemic has inflicted unprecedented pressure on communities and healthcare systems around the world. An outstandingly broad and intensive investigation of possible therapeutic interventions is currently taking place to prevent similar future threats to the global population. Investigating the related mechanisms of action is often complex and time consuming. Moreover, research on biochemical interactions of new drugs involves a considerable amount of effort, consequently bearing inherent financial and operational risks for pharmaceutical companies. An interesting approach to counteract colonization and infection is the concept of antiseptic treatment in vivo. Antiseptics are cost-effective and globally accessible, due to their ease of production, transportation and handling. A broad spectrum of active agents with different properties is readily available. One of these substances is hypochlorous acid (HOCl), which is also a naturally occurring biocidal agent and as such part of the innate immune system. Its successful history of medical use in wound treatment, combined with low cytotoxicity and documented efficacy against various pathogens, suggests that HOCl might be an effective agent for treating the respiratory mucosa. This could potentially enable therapeutic inhalation for combating bacterial infections and viral pathogens such as human respiratory syncytial, influenza, and SARS-CoV-2 viruses, which will be discussed in the present article.
References
Actimaris, Patient Information Leaflet "Actimaris Nasal Spray
Amatore, Sgarbanti, Aquilano, Baldelli, Limongi et al., Influenza virus replication in lung epithelial cells depends on redox-sensitive pathways activated by NOX4-derived ROS, Cell. Microbiol,
doi:10.1111/cmi.12343Ampiaw, Yaqub, Lee, Electrolyzed water as a disinfectant: A systematic review of factors affecting the production and efficiency of hypochlorous acid, J. Water Process Eng,
doi:10.1016/j.jwpe.2021.102228Andrés, Pérez De La Lastra, Andrés Juan, Plou, Pérez-Lebeña, Impact of Reactive Species on Amino Acids-Biological Relevance in Proteins and Induced Pathologies, Int. J. Mol. Sci,
doi:10.3390/ijms232214049Andrés, Pérez De La Lastra, Juan, Plou, Pérez-Lebeña, Hypochlorous Acid Chemistry in Mammalian Cells-Influence on Infection and Role in Various Pathologies, Int. J. Mol. Sci,
doi:10.3390/ijms231810735Antosova, Mokra, Pepucha, Plevkova, Buday et al., Physiology of nitric oxide in the respiratory system, Physiol. Res. Czech Acad. Sci,
doi:10.33549/physiolres.933673Ashby, Carlson, Scott, Redox Buffering of Hypochlorous Acid by Thiocyanate in Physiologic Fluids, J. Am. Chem. Soc,
doi:10.1021/ja0438361Barakat, Rasmy, Hosny, Kashef, Effect of povidone-iodine and propanol-based mecetronium ethyl sulphate on antimicrobial resistance and virulence in Staphylococcus aureus, Antimicrob. Resist. Infect. Control,
doi:10.1186/s13756-022-01178-9Benedusi, Tamburini, Sicurella, Summa, Ferrara et al., The Lesson Learned from the COVID-19 Pandemic: Can an Active Chemical Be Effective, Safe, Harmless-for-Humans and Low-Cost at a Time? Evidence on Aerosolized Hypochlorous Acid, Int. J. Environ. Res. Public Health,
doi:10.3390/ijerph192013163Biedro Ń, Konopi Ński, Marcinkiewicz, Józefowski, Oxidation by Neutrophils-Derived HOCl Increases Immunogenicity of Proteins by Converting Them into Ligands of Several Endocytic Receptors Involved in Antigen Uptake by Dendritic Cells and Macrophages, PLoS ONE,
doi:10.1371/journal.pone.0123293Boecker, Breves, Zhang, Bulitta, Antimicrobial Activity in the Gasphase with Hypochloric Acid, Curr. Dir. Biomed. Eng,
doi:10.1515/cdbme-2021-2130Boecker, Zhang, Breves, Herth, Kramer et al., Antimicrobial efficacy, mode of action and in vivo use of hypochlorous acid (HOCl) for prevention or therapeutic support of infections, GMS Hyg. Infect Control,
doi:10.3205/dgkh000433Briotech, Application for Inclusion in the 2021 WHO Essential Medicines List
Campbell, Kuo, Chlamydia pneumoniae-An infectious risk factor for atherosclerosis?, Nat. Rev. Microbiol,
doi:10.1038/nrmicro796Cegolon, Mirandola, Salaris, Salvati, Mastrangelo et al., Hypothiocyanite and Hypothiocyanite/Lactoferrin Mixture Exhibit Virucidal Activity In Vitro against SARS-CoV-2, Pathogens,
doi:10.3390/pathogens10020233Cespuglio, Amrouni, Meiller, Buguet, Gautier-Sauvigné, Nitric oxide in the regulation of the sleep-wake states, Sleep. Med. Rev,
doi:10.1016/j.smrv.2012.01.006Chen, Chen, Ding, Effectiveness of hypochlorous acid to reduce the biofilms on titanium alloy surfaces in vitro, Int. J. Mol. Sci,
doi:10.3390/ijms17071161Cherney, Duirk, Tarr, Collette, Monitoring the Speciation of Aqueous Free Chlorine from pH 1 to 12 with Raman Spectroscopy to Determine the Identity of the Potent Low-pH Oxidant, Appl. Spectrosc,
doi:10.1366/000370206777887062Choudhury, Shabnam, Ahsan, Kabir, Md Khan et al., Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal and Eye Drop in COVID-19 patient, Biores. Commun,
doi:10.3329/brc.v7i1.54245Darie, Khanna, Jahn, Osthoff, Bassetti et al., Fast multiplex bacterial PCR of bronchoalveolar lavage for antibiotic stewardship in hospitalised patients with pneumonia at risk of Gram-negative bacterial infection (Flagship II): A multicentre, randomised controlled trial, Lancet Respir. Med,
doi:10.1016/S2213-2600(22)00086-8Davies, Buczkowski, Welch, Green, Mawer et al., Effective in vitro inactivation of SARS-CoV-2 by commercially available mouthwashes, J. Gen. Virol,
doi:10.1099/jgv.0.001578Debnath, Mitra, Dewaker, Prabhakar, Tadala et al., Conformational perturbation of SARS-CoV-2 spike protein using N-acetyl cysteine: An exploration of probable mechanism of action to combat COVID-19, J. Biomol. Struct. Dyn,
doi:10.1080/07391102.2023.2234031Del Rosso, Bhatia, Status Report on Topical Hypochlorous Acid: Clinical Relevance of Specific Formulations, Potential Modes of Action, and Study Outcomes, J. Clin. Aesthetic Dermatol
Dickson, Erb-Downward, Freeman, Mccloskey, Beck et al., Spatial Variation in the Healthy Human Lung Microbiome and the Adapted Island Model of Lung Biogeography, Ann. Am. Thorac. Soc,
doi:10.1513/AnnalsATS.201501-029OCDominy, Lynch, Ermini, Benedyk, Marczyk et al., Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors, Sci. Adv,
doi:10.1126/sciadv.aau3333Fernández, Matthews, Seal, Intraabdominal Lavage of Hypochlorous Acid: A New Paradigm for the Septic and Open Abdomen, Wounds
Florido, Chiu, Hogg, Influenza A Virus Hemagglutinin Is Produced in Different Disulfide-Bonded States, Antioxid. Redox Signal,
doi:10.1089/ars.2021.0033Gmbh, Patient Information Leaflet "Plasma Liquid Nasal Spray Gel
Gold, Andriessen, Bhatia, Bitter, Chilukuri et al., Topical stabilized hypochlorous acid: The future gold standard for wound care and scar management in dermatologic and plastic surgery procedures, J. Cosmet. Dermatol,
doi:10.1111/jocd.13280Gorrini, Harris, Mak, Modulation of oxidative stress as an anticancer strategy, Nat. Rev. Drug Discov,
doi:10.1038/nrd4002Guan, Nuth, Weiss, Fausto, Liu et al., Rapidly Kills Corona, Flu, and Herpes to Prevent Aerosol Spread, J. Dent. Res,
doi:10.1177/00220345231169434Hacioglu, Oyardi, Yilmaz, Nagl, Comparative Fungicidal Activities of N-Chlorotaurine and Conventional Antiseptics against Candida spp. isolated from vulvovaginal candidiasis, J. Fungi,
doi:10.3390/jof8070682Hakim, Thammakarn, Suguro, Ishida, Kawamura et al., Evaluation of sprayed hypochlorous acid solutions for their virucidal activity against avian influenza virus through in vitro experiments, J. Vet. Med. Sci,
doi:10.1292/jvms.14-0413Hati, Bhattacharyya, Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin-Converting Enzyme 2 Receptor, ACS Omega,
doi:10.1021/acsomega.0c02125Held, Halko, Hurst, Mechanisms of chlorine oxidation of hydrogen peroxide, J. Am. Chem. Soc,
doi:10.1021/ja00486a025Hicks, Chaiwatpongsakorn, Costello, Mclellan, Ray et al., Five Residues in the Apical Loop of the Respiratory Syncytial Virus Fusion Protein F2 Subunit Are Critical for Its Fusion Activity, J. Virol,
doi:10.1128/JVI.00621-18Hiemstra, Mccray, Bals, The innate immune function of airway epithelial cells in inflammatory lung disease, Eur. Respir. J,
doi:10.1183/09031936.00141514Hong, Lee, Keum, Kim, Jung et al., Clinical and microbiological efficacy of pyrophosphate containing toothpaste: A double-blinded placebo-controlled randomized clinical trial, Microorganisms,
doi:10.3390/microorganisms8111806Islam, Takeyama, Role of Neutrophil Extracellular Traps in Health and Disease Pathophysiology: Recent Insights and Advances, Int. J. Mol. Sci,
doi:10.3390/ijms242115805Jandova, Snell, Hua, Dickinson, Fimbres et al., Topical hypochlorous acid (HOCl) blocks inflammatory gene expression and tumorigenic progression in UV-exposed SKH-1 high risk mouse skin, Redox Biol,
doi:10.1016/j.redox.2021.102042Jin, Piao, Cha, Kim, Taurine chloramine activates Nrf2, increases HO-1 expression and protects cells from death caused by hydrogen peroxide, J. Clin. Biochem. Nutr,
doi:10.3164/jcbn.08-262Kamal Arefin, Banu, Nasir Uddin, Nurul Fattah Rumi, Khan et al., Virucidal Effect of Povidone Iodine on SARS-CoV-2 in Nasopharynx: An Open-Label Randomized Clinical Trial, Indian. J. Otolaryngol. Head. Neck Surg,
doi:10.1007/s12070-022-03106-0Kampf, Antibiotic Resistance Can Be Enhanced in Gram-Positive Species by Some Biocidal Agents Used for Disinfection, Antibiotics,
doi:10.3390/antibiotics8010013Karimi, Crossett, Cordwell, Pattison, Davies, Characterization of disulfide (cystine) oxidation by HOCl in a model peptide: Evidence for oxygen addition, disulfide bond cleavage and adduct formation with thiols, Free Radic. Biol. Med,
doi:10.1016/j.freeradbiomed.2020.04.023Kawai, Akira, The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors, Nat. Immunol,
doi:10.1038/ni.1863Kiamco, Zmuda, Mohamed, Call, Raval et al., Hypochlorous-Acid-Generating Electrochemical Scaffold for Treatment of Wound Biofilms, Sci. Rep,
doi:10.1038/s41598-019-38968-yKramer, Eggers, Exner, Simon, Steinmann et al., Recommendation of the German Society of Hospital Hygiene (DGKH): Prevention of COVID-19 by virucidal gargling and virucidal nasal spray-Updated version April 2022, GMS Hyg. Infect. Control,
doi:10.3205/dgkh000416Kubota, Goda, Tsuru, Yonekura, Yagi et al., Efficacy and safety of strong acid electrolyzed water for peritoneal lavage to prevent surgical site infection in patients with perforated appendicitis, Surg. Today,
doi:10.1007/s00595-014-1050-xKüster, Kramer, Bremert, Langner, Hosemann et al., Eradication of MRSA skull base osteitis by combined treatment with antibiotics and sinonasal irrigation with sodium hypochlorite, Eur. Arch. Oto-Rhino-Laryngol,
doi:10.1007/s00405-015-3739-xLafon, Diem, Witting, Zaderer, Bellmann-Weiler et al., Potent SARS-CoV-2-Specific T Cell Immunity and Low Anaphylatoxin Levels Correlate with Mild Disease Progression in COVID-19 Patients, Front. Immunol,
doi:10.3389/fimmu.2021.684014Lan, Ge, Yu, Shan, Zhou et al., Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor, Nature,
doi:10.1038/s41586-020-2180-5Landino, Lessard, Lactate Dehydrogenase-B Oxidation and Inhibition by Singlet Oxygen and Hypochlorous Acid, Oxygen,
doi:10.3390/oxygen4040027Leung, Zhang, Wang, Ning, Knox et al., Topical hypochlorite ameliorates NF-κB-mediated skin diseases in mice, J. Clin. Investig,
doi:10.1172/JCI70895Li, Deng, Lei, Ding, Li et al., The Role of Oxidative Stress in Tumorigenesis and Progression, Cells,
doi:10.3390/cells13050441Ludwig, Enzenhofer, Schneider, Rauch, Bodenteich et al., Efficacy of a Carrageenan nasal spray in patients with common cold: A randomized controlled trial, Respir. Res,
doi:10.1186/1465-9921-14-124Lundberg, Weitzberg, Gladwin, The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics, Nat. Rev. Drug Discov,
doi:10.1038/nrd2466Marcinkiewicz, Grabowska, Bereta, Stelmaszynska, Taurine chloramine, a product of activated neutrophils, inhibits in vitro the generation of nitric oxide and other macrophage inflammatory mediators, J. Leukoc. Biol,
doi:10.1002/jlb.58.6.667Marcinkiewicz, Nagl, Kyriakopoulos, Walczewska, Skóra et al., Current Opinion on the Therapeutic Capacity of Taurine-Containing Halogen Derivatives in Infectious and Inflammatory Diseases, Advances in Experimental Medicine and Biology
Mcdonnell, Russell, Antiseptics and Disinfectants: Activity, Action, and Resistance, Clin. Microbiol. Rev,
doi:10.1128/CMR.12.1.147Mckenna, Davies, The inhibition of bacterial growth by hypochlorous acid. Possible role in the bactericidal activity of phagocytes, Biochem. J,
doi:10.1042/bj2540685Mclellan, Chen, Leung, Graepel, Du et al., Crystal Structure of Respiratory Syncytial Virus Fusion Glycoprotein Stabilized in the Prefusion Conformation by Human Antibody D25, Science,
doi:10.1126/science.1234914Mclellan, Yang, Graham, Kwong, Structure of Respiratory Syncytial Virus Fusion Glycoprotein in the Postfusion Conformation Reveals Preservation of Neutralizing Epitopes, J. Virol,
doi:10.1128/JVI.00555-11Mehendale, Clayton, Homyer, Reynolds, HOCl vs OCl-: Clarification on chlorine-based disinfectants used within clinical settings, J. Glob. Health Rep,
doi:10.29392/001c.84488Meister, Brüggemann, Todt, Conzelmann, Müller et al., Virucidal efficacy of different oral rinses against severe acute respiratory syndrome Coronavirus 2, J. Infect. Dis,
doi:10.1093/infdis/jiaa471Meister, Todt, Brüggemann, Steinmann, Banava et al., Virucidal activity of nasal sprays against severe acute respiratory syndrome coronavirus-2, J. Hosp. Infect,
doi:10.1016/j.jhin.2021.10.019Menta, Vidal, Friedman, Hypochlorous Acid: A Blast from the Past, J. Drugs Dermatol
Mueller, Winter, Lippert, Hochauf-Stange, Renner, Double-Blind, Randomised, Placebo-Controlled Study to Investigate the Efficacy of Nasal Spray and Mouth Wash Containing Hypochlorous Acid in SARS-CoV-2 Infected Patients
Mueller, Winter, Renner, A Concept for the Reduction of Mucosal SARS-CoV-2 Load using Hypochloric Acid Solutions, Drug Res,
doi:10.1055/a-1467-5956Nadhan, Patra, Krishnan, Rajan, Gopala et al., Perspectives on mechanistic implications of ROS inducers for targeting viral infections, Eur. J. Pharmacol,
doi:10.1016/j.ejphar.2020.173621Natarelli, Nong, Maloh, Sivamani, Hypochlorous Acid: Applications in Dermatology, J. Integr. Dermatol
Nguyen, Green, Mecsas, Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance, Front. Cell Infect. Microbiol,
doi:10.3389/fcimb.2017.00373Nizer Wsda, Inkovskiy, Overhage, Surviving reactive chlorine stress: Responses of gram-negative bacteria to hypochlorous acid, Microorganisms,
doi:10.3390/microorganisms8081220Noszticzius, Wittmann, Kály-Kullai, Beregvári, Kiss et al., Chlorine dioxide is a size-selective antimicrobial agent, PLoS ONE,
doi:10.1371/journal.pone.0079157Park, Boston, Kase, Sampson, Sobsey, Evaluation of liquid-and fog-based application of sterilox hypochlorous acid solution for surface inactivation of human norovirus, Appl. Environ. Microbiol,
doi:10.1128/AEM.02839-06Posch, Vosper, Noureen, Zaderer, Witting et al., C5aR inhibition of nonimmune cells suppresses inflammation and maintains epithelial integrity in SARS-CoV-2-infected primary human airway epithelia, J. Allergy Clin. Immunol,
doi:10.1016/j.jaci.2021.03.038Qadir Tantry, Ali, Mahmood, Hypochlorous acid decreases antioxidant power, inhibits plasma membrane redox system and pathways of glucose metabolism in human red blood cells, Toxicol Res,
doi:10.1093/toxres/tfaa111Rasmussen, Robins, Stone, Williams, Inhalation of Microaerosolized Hypochlorous Acid (HOCl): Biochemical, Antimicrobial, and Pathological Assessment, Arch. Intern. Med. Res,
doi:10.26502/aimr.0111Rayner, Zhang, Brown, Reyes, Cogger et al., Role of hypochlorous acid (HOCl) and other inflammatory mediators in the induction of macrophage extracellular trap formation, Free Radic. Biol. Med,
doi:10.1016/j.freeradbiomed.2018.09.001Robins, Keim, Robins, Edgar, Meschke et al., Modifications of IL-6 by Hypochlorous Acids: Effects on Receptor Binding, ACS Omega,
doi:10.1021/acsomega.1c05297Schrödinger, The PyMOL Molecular Graphics System
Severing, Rembe, Koester, Stuermer, Safety and efficacy profiles of different commercial sodium hypochlorite/hypochlorous acid solutions (NaClO/HClO): Antimicrobial efficacy, cytotoxic impact and physicochemical parameters in vitro, J. Antimicrob. Chemother,
doi:10.1093/jac/dky432Sismanoglu, Ercal, The cytotoxic effects of various endodontic irrigants on the viability of dental mesenchymal stem cells, Aust. Endod. J,
doi:10.1111/aej.12570Snell, Jandova, Wondrak, Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer, Front. Oncol,
doi:10.3389/fonc.2022.887220Storkey, Davies, Pattison, Reevaluation of the rate constants for the reaction of hypochlorous acid (HOCl) with cysteine, methionine, and peptide derivatives using a new competition kinetic approach, Free Radic. Biol. Med,
doi:10.1016/j.freeradbiomed.2014.04.024Stroman, Mintun, Epstein, Brimer, Patel et al., Reduction in bacterial load using hypochlorous acid hygiene solution on ocular skin, Clin. Ophthalmol,
doi:10.2147/OPTH.S132851Tamaki, Bui, Ngo, Ogawa, Imai, Virucidal effect of acidic electrolyzed water and neutral electrolyzed water on avian influenza viruses, Arch. Virol,
doi:10.1007/s00705-013-1840-2Tazawa, Jadhav, Azuma, Fenno, Mcdonald et al., Hypochlorous acid inactivates oral pathogens and a SARS-CoV-2-surrogate, BMC Oral Health,
doi:10.1186/s12903-023-02820-7Tribble, Angelov, Weltman, Wang, Eswaran et al., Frequency of tongue cleaning impacts the human tongue microbiome composition and enterosalivary circulation of nitrate, Front. Cell. Infect. Microbiol,
doi:10.3389/fcimb.2019.00039Ulfig, Leichert, The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens, Cell. Mol. Life Sci,
doi:10.1007/s00018-020-03591-yUrushidani, Kawayoshi, Kotaki, Saeki, Mori et al., Inactivation of SARS-CoV-2 and influenza A virus by dry fogging hypochlorous acid solution and hydrogen peroxide solution, PLoS ONE,
doi:10.1371/journal.pone.0261802Venkitanarayanan, Ezeike, Hung, Doyle, Inactivation of Escherichia coli O157:H7 and Listeria monocytogenes on Plastic Kitchen Cutting Boards by Electrolyzed Oxidizing Water, J. Food Prot,
doi:10.4315/0362-028X-62.8.857Whitsett, Alenghat, Respiratory epithelial cells orchestrate pulmonary innate immunity, Nat. Immunol,
doi:10.1038/ni.3045Worbs, Hammerschmidt, Förster, Dendritic cell migration in health and disease, Nat. Rev. Immunol,
doi:10.1038/nri.2016.116Wright, Immunoregulatory functions of surfactant proteins, Nat. Rev. Immunol,
doi:10.1038/nri1528Yang, Chuang, Huang, Fang, Inactivation of Avian Influenza Virus Aerosol Using Membrane-Less Electrolyzed Water Spraying, Aerobiology,
doi:10.3390/aerobiology1020006Yu, Park, Kwon, Jang, The Effect of a Low Concentration of Hypochlorous Acid on Rhinovirus Infection of Nasal Epithelial Cells, Am. J. Rhinol. Allergy,
doi:10.2500/ajra.2011.25.3545Zayed, Vertommen, Simoens, Bernaerts, Boon et al., How well do antimicrobial mouth rinses prevent dysbiosis in an in vitro periodontitis biofilm model?, J. Periodontol,
doi:10.1002/JPER.23-0674Zgliczy Ński, Stelmaszy Ńska, Doma Ński, Ostrowski, Chloramines as intermediates of oxidation reaction of amino acids by myeloperoxidase, Biochim. Biophys. Acta (BBA) Enzymol,
doi:10.1016/0005-2744(71)90281-6Zhao, Xin, Zhao, Zheng, Tian et al., Free chlorine loss during spraying of membraneless acidic electrolyzed water and its antimicrobial effect on airborne bacteria from poultry house, Ann. Agric. Environ. Med,
doi:10.5604/1232-1966.1108585Zwicker, Freitag, Heidel, Kocher, Kramer, Antiseptic efficacy of two mouth rinses in the oral cavity to identify a suitable rinsing solution in radiation-or chemotherapy induced mucositis, BMC Oral Health,
doi:10.1186/s12903-023-02884-5DOI record:
{
"DOI": "10.3390/v17091219",
"ISSN": [
"1999-4915"
],
"URL": "http://dx.doi.org/10.3390/v17091219",
"abstract": "<jats:p>The COVID-19 pandemic has inflicted unprecedented pressure on communities and healthcare systems around the world. An outstandingly broad and intensive investigation of possible therapeutic interventions is currently taking place to prevent similar future threats to the global population. Investigating the related mechanisms of action is often complex and time consuming. Moreover, research on biochemical interactions of new drugs involves a considerable amount of effort, consequently bearing inherent financial and operational risks for pharmaceutical companies. An interesting approach to counteract colonization and infection is the concept of antiseptic treatment in vivo. Antiseptics are cost-effective and globally accessible, due to their ease of production, transportation and handling. A broad spectrum of active agents with different properties is readily available. One of these substances is hypochlorous acid (HOCl), which is also a naturally occurring biocidal agent and as such part of the innate immune system. Its successful history of medical use in wound treatment, combined with low cytotoxicity and documented efficacy against various pathogens, suggests that HOCl might be an effective agent for treating the respiratory mucosa. This could potentially enable therapeutic inhalation for combating bacterial infections and viral pathogens such as human respiratory syncytial, influenza, and SARS-CoV-2 viruses, which will be discussed in the present article.</jats:p>",
"alternative-id": [
"v17091219"
],
"author": [
{
"ORCID": "https://orcid.org/0000-0003-4667-576X",
"affiliation": [
{
"name": "Team Winter Kompetenztraining, 1030 Vienna, Austria"
}
],
"authenticated-orcid": false,
"family": "Winter",
"given": "Michael",
"sequence": "first"
},
{
"affiliation": [
{
"name": "TOTO Consulting LLC, Campbell, CA 95080, USA"
}
],
"family": "Boecker",
"given": "Dirk",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0001-8955-7654",
"affiliation": [
{
"name": "Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Schöpfstrasse 41/R311, 6020 Innsbruck, Austria"
}
],
"authenticated-orcid": false,
"family": "Posch",
"given": "Wilfried",
"sequence": "additional"
}
],
"container-title": "Viruses",
"container-title-short": "Viruses",
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2025,
9,
8
]
],
"date-time": "2025-09-08T08:06:32Z",
"timestamp": 1757318792000
},
"deposited": {
"date-parts": [
[
2025,
10,
9
]
],
"date-time": "2025-10-09T18:41:27Z",
"timestamp": 1760035287000
},
"funder": [
{
"name": "Austrian Science Fund (FWF)"
}
],
"indexed": {
"date-parts": [
[
2025,
10,
10
]
],
"date-time": "2025-10-10T01:41:57Z",
"timestamp": 1760060517203,
"version": "build-2065373602"
},
"is-referenced-by-count": 0,
"issue": "9",
"issued": {
"date-parts": [
[
2025,
9,
7
]
]
},
"journal-issue": {
"issue": "9",
"published-online": {
"date-parts": [
[
2025,
9
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://creativecommons.org/licenses/by/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
9,
7
]
],
"date-time": "2025-09-07T00:00:00Z",
"timestamp": 1757203200000
}
}
],
"link": [
{
"URL": "https://www.mdpi.com/1999-4915/17/9/1219/pdf",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "1968",
"original-title": [],
"page": "1219",
"prefix": "10.3390",
"published": {
"date-parts": [
[
2025,
9,
7
]
]
},
"published-online": {
"date-parts": [
[
2025,
9,
7
]
]
},
"publisher": "MDPI AG",
"reference": [
{
"DOI": "10.1038/s41429-023-00629-8",
"article-title": "Antibiotics in the clinical pipeline as of December 2022",
"author": "Butler",
"doi-asserted-by": "crossref",
"first-page": "431",
"journal-title": "J. Antibiot.",
"key": "ref_1",
"volume": "76",
"year": "2023"
},
{
"DOI": "10.1186/s12903-023-02820-7",
"doi-asserted-by": "crossref",
"key": "ref_2",
"unstructured": "Tazawa, K., Jadhav, R., Azuma, M.M., Fenno, J.C., McDonald, N.J., and Sasaki, H. (2023). Hypochlorous acid inactivates oral pathogens and a SARS-CoV-2-surrogate. BMC Oral Health, 23."
},
{
"article-title": "Antimicrobial efficacy, mode of action and in vivo use of hypochlorous acid (HOCl) for prevention or therapeutic support of infections",
"author": "Boecker",
"first-page": "Doc07",
"journal-title": "GMS Hyg. Infect Control",
"key": "ref_3",
"volume": "18",
"year": "2023"
},
{
"DOI": "10.1038/s41598-019-38968-y",
"doi-asserted-by": "crossref",
"key": "ref_4",
"unstructured": "Kiamco, M.M., Zmuda, H.M., Mohamed, A., Call, D.R., Raval, Y.S., Patel, R., and Beyenal, H. (2019). Hypochlorous-Acid-Generating Electrochemical Scaffold for Treatment of Wound Biofilms. Sci. Rep., 9."
},
{
"DOI": "10.1186/s13756-022-01178-9",
"article-title": "Effect of povidone-iodine and propanol-based mecetronium ethyl sulphate on antimicrobial resistance and virulence in Staphylococcus aureus",
"author": "Barakat",
"doi-asserted-by": "crossref",
"first-page": "139",
"journal-title": "Antimicrob. Resist. Infect. Control",
"key": "ref_5",
"volume": "11",
"year": "2022"
},
{
"DOI": "10.3390/ijms17071161",
"doi-asserted-by": "crossref",
"key": "ref_6",
"unstructured": "Chen, C.J., Chen, C.C., and Ding, S.J. (2016). Effectiveness of hypochlorous acid to reduce the biofilms on titanium alloy surfaces in vitro. Int. J. Mol. Sci., 17."
},
{
"DOI": "10.3390/jof8070682",
"doi-asserted-by": "crossref",
"key": "ref_7",
"unstructured": "Hacioglu, M., Oyardi, O., Yilmaz, F.N., and Nagl, M. (2022). Comparative Fungicidal Activities of N-Chlorotaurine and Conventional Antiseptics against Candida spp. isolated from vulvovaginal candidiasis. J. Fungi, 8."
},
{
"DOI": "10.1007/s00705-013-1840-2",
"article-title": "Virucidal effect of acidic electrolyzed water and neutral electrolyzed water on avian influenza viruses",
"author": "Tamaki",
"doi-asserted-by": "crossref",
"first-page": "405",
"journal-title": "Arch. Virol.",
"key": "ref_8",
"volume": "159",
"year": "2014"
},
{
"DOI": "10.1007/s12070-022-03106-0",
"article-title": "Virucidal Effect of Povidone Iodine on SARS-CoV-2 in Nasopharynx: An Open-Label Randomized Clinical Trial",
"author": "Banu",
"doi-asserted-by": "crossref",
"first-page": "3283",
"journal-title": "Indian. J. Otolaryngol. Head. Neck Surg.",
"key": "ref_9",
"volume": "74",
"year": "2022"
},
{
"DOI": "10.1093/infdis/jiaa471",
"article-title": "Virucidal efficacy of different oral rinses against severe acute respiratory syndrome Coronavirus 2",
"author": "Meister",
"doi-asserted-by": "crossref",
"first-page": "1289",
"journal-title": "J. Infect. Dis.",
"key": "ref_10",
"volume": "222",
"year": "2020"
},
{
"article-title": "Recommendation of the German Society of Hospital Hygiene (DGKH): Prevention of COVID-19 by virucidal gargling and virucidal nasal spray—Updated version April 2022",
"author": "Kramer",
"first-page": "Doc13",
"journal-title": "GMS Hyg. Infect. Control",
"key": "ref_11",
"volume": "17",
"year": "2022"
},
{
"DOI": "10.3329/brc.v7i1.54245",
"article-title": "Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal and Eye Drop in COVID-19 patient",
"author": "Choudhury",
"doi-asserted-by": "crossref",
"first-page": "919",
"journal-title": "Biores. Commun.",
"key": "ref_12",
"volume": "7",
"year": "2021"
},
{
"DOI": "10.1099/jgv.0.001578",
"article-title": "Effective in vitro inactivation of SARS-CoV-2 by commercially available mouthwashes",
"author": "Davies",
"doi-asserted-by": "crossref",
"first-page": "001578",
"journal-title": "J. Gen. Virol.",
"key": "ref_13",
"volume": "102",
"year": "2021"
},
{
"DOI": "10.1186/1465-9921-14-124",
"article-title": "Efficacy of a Carrageenan nasal spray in patients with common cold: A randomized controlled trial",
"author": "Ludwig",
"doi-asserted-by": "crossref",
"first-page": "124",
"journal-title": "Respir. Res.",
"key": "ref_14",
"volume": "14",
"year": "2013"
},
{
"DOI": "10.1016/j.jhin.2021.10.019",
"article-title": "Virucidal activity of nasal sprays against severe acute respiratory syndrome coronavirus-2",
"author": "Meister",
"doi-asserted-by": "crossref",
"first-page": "9",
"journal-title": "J. Hosp. Infect.",
"key": "ref_15",
"volume": "120",
"year": "2022"
},
{
"DOI": "10.1007/978-3-030-93337-1_8",
"article-title": "Current Opinion on the Therapeutic Capacity of Taurine-Containing Halogen Derivatives in Infectious and Inflammatory Diseases",
"author": "Schaffer",
"doi-asserted-by": "crossref",
"first-page": "83",
"journal-title": "Taurine 12",
"key": "ref_16",
"volume": "Volume 1370",
"year": "2022"
},
{
"DOI": "10.1183/09031936.00141514",
"article-title": "The innate immune function of airway epithelial cells in inflammatory lung disease",
"author": "Hiemstra",
"doi-asserted-by": "crossref",
"first-page": "1150",
"journal-title": "Eur. Respir. J.",
"key": "ref_17",
"volume": "45",
"year": "2015"
},
{
"DOI": "10.1007/s00405-015-3739-x",
"article-title": "Eradication of MRSA skull base osteitis by combined treatment with antibiotics and sinonasal irrigation with sodium hypochlorite",
"author": "Kramer",
"doi-asserted-by": "crossref",
"first-page": "1951",
"journal-title": "Eur. Arch. Oto-Rhino-Laryngol.",
"key": "ref_18",
"volume": "273",
"year": "2016"
},
{
"DOI": "10.3389/fcimb.2017.00373",
"doi-asserted-by": "crossref",
"key": "ref_19",
"unstructured": "Nguyen, G.T., Green, E.R., and Mecsas, J. (2017). Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance. Front. Cell Infect. Microbiol., 7."
},
{
"DOI": "10.3390/ijms231810735",
"doi-asserted-by": "crossref",
"key": "ref_20",
"unstructured": "Andrés, C.M.C., Pérez de la Lastra, J.M., Juan, C.A., Plou, F.J., and Pérez-Lebeña, E. (2022). Hypochlorous Acid Chemistry in Mammalian Cells—Influence on Infection and Role in Various Pathologies. Int. J. Mol. Sci., 23."
},
{
"DOI": "10.1007/s00018-020-03591-y",
"article-title": "The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens",
"author": "Ulfig",
"doi-asserted-by": "crossref",
"first-page": "385",
"journal-title": "Cell. Mol. Life Sci.",
"key": "ref_21",
"volume": "78",
"year": "2021"
},
{
"DOI": "10.1016/j.joms.2020.06.029",
"article-title": "Hypochlorous Acid: A Review",
"author": "Block",
"doi-asserted-by": "crossref",
"first-page": "1461",
"journal-title": "J. Oral Maxillofac. Surg.",
"key": "ref_22",
"volume": "78",
"year": "2020"
},
{
"DOI": "10.1016/j.jwpe.2021.102228",
"article-title": "Electrolyzed water as a disinfectant: A systematic review of factors affecting the production and efficiency of hypochlorous acid",
"author": "Ampiaw",
"doi-asserted-by": "crossref",
"first-page": "102228",
"journal-title": "J. Water Process Eng.",
"key": "ref_23",
"volume": "43",
"year": "2021"
},
{
"key": "ref_24",
"unstructured": "USDA (2024, April 06). Hypochlorous Acid. Technical Evaluation Report, Available online: https://www.ams.usda.gov/sites/default/files/media/Hypochlorous%20Acid%20TR%2008%2013%2015.pdf."
},
{
"key": "ref_25",
"unstructured": "Briotech, Inc. (2025, September 04). Application for Inclusion in the 2021 WHO Essential Medicines List. Available online: https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/23rd-expert-committee/a18-hypochlorous."
},
{
"DOI": "10.1366/000370206777887062",
"article-title": "Monitoring the Speciation of Aqueous Free Chlorine from pH 1 to 12 with Raman Spectroscopy to Determine the Identity of the Potent Low-pH Oxidant",
"author": "Cherney",
"doi-asserted-by": "crossref",
"first-page": "764",
"journal-title": "Appl. Spectrosc.",
"key": "ref_26",
"volume": "60",
"year": "2006"
},
{
"DOI": "10.1111/jocd.13280",
"article-title": "Topical stabilized hypochlorous acid: The future gold standard for wound care and scar management in dermatologic and plastic surgery procedures",
"author": "Gold",
"doi-asserted-by": "crossref",
"first-page": "270",
"journal-title": "J. Cosmet. Dermatol.",
"key": "ref_27",
"volume": "19",
"year": "2020"
},
{
"DOI": "10.1016/j.freeradbiomed.2018.09.001",
"article-title": "Role of hypochlorous acid (HOCl) and other inflammatory mediators in the induction of macrophage extracellular trap formation",
"author": "Rayner",
"doi-asserted-by": "crossref",
"first-page": "25",
"journal-title": "Free Radic. Biol. Med.",
"key": "ref_28",
"volume": "129",
"year": "2018"
},
{
"DOI": "10.20944/preprints202309.1883.v1",
"doi-asserted-by": "crossref",
"key": "ref_29",
"unstructured": "Islam, M.d.M., and Takeyama, N. (2023). Role of Neutrophil Extracellular Traps in Health and Disease Pathophysiology: Recent Insights and Advances. Int. J. Mol. Sci., 24."
},
{
"DOI": "10.1371/journal.pone.0123293",
"doi-asserted-by": "crossref",
"key": "ref_30",
"unstructured": "Biedroń, R., Konopiński, M.K., Marcinkiewicz, J., and Józefowski, S. (2015). Oxidation by Neutrophils-Derived HOCl Increases Immunogenicity of Proteins by Converting Them into Ligands of Several Endocytic Receptors Involved in Antigen Uptake by Dendritic Cells and Macrophages. PLoS ONE, 10."
},
{
"DOI": "10.1016/0005-2744(71)90281-6",
"article-title": "Chloramines as intermediates of oxidation reaction of amino acids by myeloperoxidase",
"author": "Ostrowski",
"doi-asserted-by": "crossref",
"first-page": "419",
"journal-title": "Biochim. Biophys. Acta (BBA) Enzymol.",
"key": "ref_31",
"volume": "235",
"year": "1971"
},
{
"DOI": "10.1101/036103",
"doi-asserted-by": "crossref",
"key": "ref_32",
"unstructured": "Sender, R., Fuchs, S., and Milo, R. (2016). Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol., 14."
},
{
"DOI": "10.1038/nature11234",
"doi-asserted-by": "crossref",
"key": "ref_33",
"unstructured": "Human Microbiome Project Consortium (2012). Structure, function and diversity of the healthy human microbiome. Nature, 486, 207–214."
},
{
"DOI": "10.1038/nrmicro796",
"article-title": "Chlamydia pneumoniae—An infectious risk factor for atherosclerosis?",
"author": "Campbell",
"doi-asserted-by": "crossref",
"first-page": "23",
"journal-title": "Nat. Rev. Microbiol.",
"key": "ref_34",
"volume": "2",
"year": "2004"
},
{
"DOI": "10.1371/journal.pone.0151081",
"doi-asserted-by": "crossref",
"key": "ref_35",
"unstructured": "Ide, M., Harris, M., Stevens, A., Sussams, R., Hopkins, V., Culliford, D., Fuller, J., Ibbett, P., Raybould, R., and Thomas, R. (2016). Periodontitis and Cognitive Decline in Alzheimer’s Disease. PLoS ONE, 11."
},
{
"DOI": "10.1126/sciadv.aau3333",
"article-title": "Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors",
"author": "Dominy",
"doi-asserted-by": "crossref",
"first-page": "eaau3333",
"journal-title": "Sci. Adv.",
"key": "ref_36",
"volume": "5",
"year": "2019"
},
{
"DOI": "10.1038/nrdp.2017.38",
"article-title": "Periodontal diseases",
"author": "Kinane",
"doi-asserted-by": "crossref",
"first-page": "17038",
"journal-title": "Nat. Rev. Dis. Primers",
"key": "ref_37",
"volume": "3",
"year": "2017"
},
{
"DOI": "10.1038/nrd2466",
"article-title": "The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics",
"author": "Lundberg",
"doi-asserted-by": "crossref",
"first-page": "156",
"journal-title": "Nat. Rev. Drug Discov.",
"key": "ref_38",
"volume": "7",
"year": "2008"
},
{
"DOI": "10.3389/fcimb.2019.00039",
"doi-asserted-by": "crossref",
"key": "ref_39",
"unstructured": "Tribble, G.D., Angelov, N., Weltman, R., Wang, B.Y., Eswaran, S.V., Gay, I.C., Parthasarathy, K., Dao, D.H.V., Richardson, K.N., and Ismail, N.M. (2019). Frequency of tongue cleaning impacts the human tongue microbiome composition and enterosalivary circulation of nitrate. Front. Cell. Infect. Microbiol., 9."
},
{
"DOI": "10.1016/j.smrv.2012.01.006",
"article-title": "Nitric oxide in the regulation of the sleep-wake states",
"author": "Cespuglio",
"doi-asserted-by": "crossref",
"first-page": "265",
"journal-title": "Sleep. Med. Rev.",
"key": "ref_40",
"volume": "16",
"year": "2012"
},
{
"DOI": "10.1056/NEJMra0910061",
"article-title": "Airway Mucus Function and Dysfunction",
"author": "Fahy",
"doi-asserted-by": "crossref",
"first-page": "2233",
"journal-title": "N. Engl. J. Med.",
"key": "ref_41",
"volume": "363",
"year": "2010"
},
{
"DOI": "10.1038/nri.2016.116",
"article-title": "Dendritic cell migration in health and disease",
"author": "Worbs",
"doi-asserted-by": "crossref",
"first-page": "30",
"journal-title": "Nat. Rev. Immunol.",
"key": "ref_42",
"volume": "17",
"year": "2017"
},
{
"DOI": "10.1038/ni.3045",
"article-title": "Respiratory epithelial cells orchestrate pulmonary innate immunity",
"author": "Whitsett",
"doi-asserted-by": "crossref",
"first-page": "27",
"journal-title": "Nat. Immunol.",
"key": "ref_43",
"volume": "16",
"year": "2015"
},
{
"DOI": "10.1016/j.cell.2006.02.015",
"article-title": "Pathogen Recognition and Innate Immunity",
"author": "Akira",
"doi-asserted-by": "crossref",
"first-page": "783",
"journal-title": "Cell",
"key": "ref_44",
"volume": "124",
"year": "2006"
},
{
"DOI": "10.1038/ni.1863",
"article-title": "The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors",
"author": "Kawai",
"doi-asserted-by": "crossref",
"first-page": "373",
"journal-title": "Nat. Immunol.",
"key": "ref_45",
"volume": "11",
"year": "2010"
},
{
"DOI": "10.1101/cshperspect.a016295",
"doi-asserted-by": "crossref",
"key": "ref_46",
"unstructured": "Tanaka, T., Narazaki, M., and Kishimoto, T. (2014). IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harb. Perspect. Biol., 6."
},
{
"DOI": "10.1038/nri1528",
"article-title": "Immunoregulatory functions of surfactant proteins",
"author": "Wright",
"doi-asserted-by": "crossref",
"first-page": "58",
"journal-title": "Nat. Rev. Immunol.",
"key": "ref_47",
"volume": "5",
"year": "2005"
},
{
"DOI": "10.1111/j.0105-2896.2005.00290.x",
"article-title": "Mucosal immunoglobulins",
"author": "Woof",
"doi-asserted-by": "crossref",
"first-page": "64",
"journal-title": "Immunol. Rev.",
"key": "ref_48",
"volume": "206",
"year": "2005"
},
{
"DOI": "10.1513/AnnalsATS.201501-029OC",
"article-title": "Spatial Variation in the Healthy Human Lung Microbiome and the Adapted Island Model of Lung Biogeography",
"author": "Dickson",
"doi-asserted-by": "crossref",
"first-page": "821",
"journal-title": "Ann. Am. Thorac. Soc.",
"key": "ref_49",
"volume": "12",
"year": "2015"
},
{
"DOI": "10.2147/OPTH.S132851",
"article-title": "Reduction in bacterial load using hypochlorous acid hygiene solution on ocular skin",
"author": "Stroman",
"doi-asserted-by": "crossref",
"first-page": "707",
"journal-title": "Clin. Ophthalmol.",
"key": "ref_50",
"volume": "11",
"year": "2017"
},
{
"DOI": "10.3390/microorganisms8111806",
"doi-asserted-by": "crossref",
"key": "ref_51",
"unstructured": "Hong, I., Lee, H.G., Keum, H.L., Kim, M.J., Jung, U.W., Kim, K., Kim, S.Y., Park, T., Kim, H.J., and Kim, J.J. (2020). Clinical and microbiological efficacy of pyrophosphate containing toothpaste: A double-blinded placebo-controlled randomized clinical trial. Microorganisms, 8."
},
{
"DOI": "10.1002/JPER.23-0674",
"article-title": "How well do antimicrobial mouth rinses prevent dysbiosis in an in vitro periodontitis biofilm model?",
"author": "Zayed",
"doi-asserted-by": "crossref",
"first-page": "880",
"journal-title": "J. Periodontol.",
"key": "ref_52",
"volume": "95",
"year": "2024"
},
{
"key": "ref_53",
"unstructured": "U.S. Food & Drug Administration (2025, July 03). 510(k) Premarket Notification—Spectricept Skin and Wound Cleanser (K213514), Available online: https://www.accessdata.fda.gov/cdrh_docs/pdf21/K213514.pdf."
},
{
"key": "ref_54",
"unstructured": "U.S. Food & Drug Administration (2025, July 02). 510(k) Premarket Notification—Microdacyn Wound Care Solution (K233399), Available online: https://www.accessdata.fda.gov/cdrh_docs/pdf23/K233399.pdf."
},
{
"article-title": "Status Report on Topical Hypochlorous Acid: Clinical Relevance of Specific Formulations, Potential Modes of Action, and Study Outcomes",
"author": "Bhatia",
"first-page": "36",
"journal-title": "J. Clin. Aesthetic Dermatol.",
"key": "ref_55",
"volume": "11",
"year": "2018"
},
{
"article-title": "Hypochlorous Acid: A Blast from the Past",
"author": "Menta",
"first-page": "909",
"journal-title": "J. Drugs Dermatol.",
"key": "ref_56",
"volume": "23",
"year": "2024"
},
{
"key": "ref_57",
"unstructured": "Regeno GmbH (2022). Patient Information Leaflet “Plasma Liquid Nasal Spray Gel.”, Regeno, GmbH."
},
{
"DOI": "10.1093/jac/dky432",
"article-title": "Safety and efficacy profiles of different commercial sodium hypochlorite/hypochlorous acid solutions (NaClO/HClO): Antimicrobial efficacy, cytotoxic impact and physicochemical parameters in vitro",
"author": "Severing",
"doi-asserted-by": "crossref",
"first-page": "365",
"journal-title": "J. Antimicrob. Chemother.",
"key": "ref_58",
"volume": "74",
"year": "2019"
},
{
"key": "ref_59",
"unstructured": "(2024). Arbeitsplatzgrenzwerte (Standard No. TRGS 900)."
},
{
"key": "ref_60",
"unstructured": "Actimaris, A.G. (2020). Patient Information Leaflet “Actimaris Nasal Spray.”, Actimaris, A.G."
},
{
"DOI": "10.1111/aej.12570",
"article-title": "The cytotoxic effects of various endodontic irrigants on the viability of dental mesenchymal stem cells",
"author": "Sismanoglu",
"doi-asserted-by": "crossref",
"first-page": "305",
"journal-title": "Aust. Endod. J.",
"key": "ref_61",
"volume": "48",
"year": "2022"
},
{
"article-title": "HOCl vs OCl−: Clarification on chlorine-based disinfectants used within clinical settings",
"author": "Mehendale",
"first-page": "e2023052",
"journal-title": "J. Glob. Health Rep.",
"key": "ref_62",
"volume": "7",
"year": "2023"
},
{
"DOI": "10.3390/ijerph192013163",
"doi-asserted-by": "crossref",
"key": "ref_63",
"unstructured": "Benedusi, M., Tamburini, E., Sicurella, M., Summa, D., Ferrara, F., Marconi, P., Cervellati, F., Costa, S., and Valacchi, G. (2022). The Lesson Learned from the COVID-19 Pandemic: Can an Active Chemical Be Effective, Safe, Harmless-for-Humans and Low-Cost at a Time? Evidence on Aerosolized Hypochlorous Acid. Int. J. Environ. Res. Public Health, 19."
},
{
"DOI": "10.1371/journal.pone.0304602",
"doi-asserted-by": "crossref",
"key": "ref_64",
"unstructured": "Lewandowski, R.B., Stȩpińska, M., Osuchowski, Ł., Kasprzycka, W., Dobrzyńska, M., Mierczyk, Z., and Trafny, E.A. (2024). The HOCl dry fog-is it safe for human cells?. PLoS ONE, 19."
},
{
"DOI": "10.1515/cdbme-2021-2130",
"article-title": "Antimicrobial Activity in the Gasphase with Hypochloric Acid",
"author": "Boecker",
"doi-asserted-by": "crossref",
"first-page": "511",
"journal-title": "Curr. Dir. Biomed. Eng.",
"key": "ref_65",
"volume": "7",
"year": "2021"
},
{
"DOI": "10.26502/aimr.0111",
"article-title": "Inhalation of Microaerosolized Hypochlorous Acid (HOCl): Biochemical, Antimicrobial, and Pathological Assessment",
"author": "Rasmussen",
"doi-asserted-by": "crossref",
"first-page": "311",
"journal-title": "Arch. Intern. Med. Res.",
"key": "ref_66",
"volume": "05",
"year": "2022"
},
{
"DOI": "10.1371/journal.pone.0079157",
"doi-asserted-by": "crossref",
"key": "ref_67",
"unstructured": "Noszticzius, Z., Wittmann, M., Kály-Kullai, K., Beregvári, Z., Kiss, I., Rosivall, L., and Szegedi, J. (2013). Chlorine dioxide is a size-selective antimicrobial agent. PLoS ONE, 8."
},
{
"DOI": "10.1002/j.2040-4603.2020.tb00124.x",
"article-title": "Bioengineering the blood-gas barrier",
"author": "Leiby",
"doi-asserted-by": "crossref",
"first-page": "415",
"journal-title": "Compr. Physiol.",
"key": "ref_68",
"volume": "10",
"year": "2020"
},
{
"DOI": "10.1093/toxres/tfaa111",
"article-title": "Hypochlorous acid decreases antioxidant power, inhibits plasma membrane redox system and pathways of glucose metabolism in human red blood cells",
"author": "Ali",
"doi-asserted-by": "crossref",
"first-page": "264",
"journal-title": "Toxicol Res.",
"key": "ref_69",
"volume": "10",
"year": "2021"
},
{
"DOI": "10.3164/jcbn.08-262",
"article-title": "Taurine chloramine activates Nrf2, increases HO-1 expression and protects cells from death caused by hydrogen peroxide",
"author": "Jin",
"doi-asserted-by": "crossref",
"first-page": "37",
"journal-title": "J. Clin. Biochem. Nutr.",
"key": "ref_70",
"volume": "45",
"year": "2009"
},
{
"DOI": "10.1007/0-306-46838-7_60",
"article-title": "Cytoprotective Effect of Taurine Against Hypochlorous Acid Toxicity to PC12 Cells",
"author": "Huxtable",
"doi-asserted-by": "crossref",
"first-page": "563",
"journal-title": "Taurine 4; Advances in Experimental Medicine and Biology",
"key": "ref_71",
"volume": "Volume 483",
"year": "2002"
},
{
"article-title": "Physiology of nitric oxide in the respiratory system",
"author": "Antosova",
"first-page": "S159",
"journal-title": "Physiol. Res. Czech Acad. Sci.",
"key": "ref_72",
"volume": "66",
"year": "2017"
},
{
"DOI": "10.1016/j.freeradbiomed.2014.04.024",
"article-title": "Reevaluation of the rate constants for the reaction of hypochlorous acid (HOCl) with cysteine, methionine, and peptide derivatives using a new competition kinetic approach",
"author": "Storkey",
"doi-asserted-by": "crossref",
"first-page": "60",
"journal-title": "Free Radic. Biol. Med.",
"key": "ref_73",
"volume": "73",
"year": "2014"
},
{
"DOI": "10.1021/ja0438361",
"article-title": "Redox Buffering of Hypochlorous Acid by Thiocyanate in Physiologic Fluids",
"author": "Ashby",
"doi-asserted-by": "crossref",
"first-page": "15976",
"journal-title": "J. Am. Chem. Soc.",
"key": "ref_74",
"volume": "126",
"year": "2004"
},
{
"DOI": "10.3390/pathogens10020233",
"doi-asserted-by": "crossref",
"key": "ref_75",
"unstructured": "Cegolon, L., Mirandola, M., Salaris, C., Salvati, M.V., Mastrangelo, G., and Salata, C. (2021). Hypothiocyanite and Hypothiocyanite/Lactoferrin Mixture Exhibit Virucidal Activity In Vitro against SARS-CoV-2. Pathogens, 10."
},
{
"DOI": "10.1016/bs.ircmb.2018.05.002",
"article-title": "Mitohormesis, an Antiaging Paradigm",
"author": "Mayoral",
"doi-asserted-by": "crossref",
"first-page": "35",
"journal-title": "Int. Rev. Cell. Mol. Biol.",
"key": "ref_76",
"volume": "340",
"year": "2018"
},
{
"DOI": "10.1016/j.freeradbiomed.2015.11.032",
"article-title": "Mitohormesis in exercise training",
"author": "Merry",
"doi-asserted-by": "crossref",
"first-page": "123",
"journal-title": "Free Radic. Biol. Med.",
"key": "ref_77",
"volume": "98",
"year": "2016"
},
{
"DOI": "10.1128/CMR.12.1.147",
"article-title": "Antiseptics and Disinfectants: Activity, Action, and Resistance",
"author": "McDonnell",
"doi-asserted-by": "crossref",
"first-page": "147",
"journal-title": "Clin. Microbiol. Rev.",
"key": "ref_78",
"volume": "12",
"year": "1999"
},
{
"DOI": "10.1042/bj2540685",
"article-title": "The inhibition of bacterial growth by hypochlorous acid. Possible role in the bactericidal activity of phagocytes",
"author": "McKenna",
"doi-asserted-by": "crossref",
"first-page": "685",
"journal-title": "Biochem. J.",
"key": "ref_79",
"volume": "254",
"year": "1988"
},
{
"DOI": "10.1016/j.ejphar.2020.173621",
"article-title": "Perspectives on mechanistic implications of ROS inducers for targeting viral infections",
"author": "Nadhan",
"doi-asserted-by": "crossref",
"first-page": "173621",
"journal-title": "Eur. J. Pharmacol.",
"key": "ref_80",
"volume": "890",
"year": "2021"
},
{
"DOI": "10.1038/s44298-025-00110-3",
"article-title": "Effects of oxidative stress on viral infections: An overview",
"author": "Kayesh",
"doi-asserted-by": "crossref",
"first-page": "27",
"journal-title": "npj Viruses",
"key": "ref_81",
"volume": "3",
"year": "2025"
},
{
"DOI": "10.1021/acsomega.0c02125",
"article-title": "Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin-Converting Enzyme 2 Receptor",
"author": "Hati",
"doi-asserted-by": "crossref",
"first-page": "16292",
"journal-title": "ACS Omega",
"key": "ref_82",
"volume": "5",
"year": "2020"
},
{
"DOI": "10.1016/j.freeradbiomed.2020.04.023",
"article-title": "Characterization of disulfide (cystine) oxidation by HOCl in a model peptide: Evidence for oxygen addition, disulfide bond cleavage and adduct formation with thiols",
"author": "Karimi",
"doi-asserted-by": "crossref",
"first-page": "62",
"journal-title": "Free Radic. Biol. Med.",
"key": "ref_83",
"volume": "154",
"year": "2020"
},
{
"DOI": "10.3390/oxygen4040027",
"article-title": "Lactate Dehydrogenase-B Oxidation and Inhibition by Singlet Oxygen and Hypochlorous Acid",
"author": "Landino",
"doi-asserted-by": "crossref",
"first-page": "432",
"journal-title": "Oxygen",
"key": "ref_84",
"volume": "4",
"year": "2024"
},
{
"DOI": "10.1038/s41586-020-2180-5",
"article-title": "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor",
"author": "Lan",
"doi-asserted-by": "crossref",
"first-page": "215",
"journal-title": "Nature",
"key": "ref_85",
"volume": "581",
"year": "2020"
},
{
"key": "ref_86",
"unstructured": "Schrödinger, L.L.C. (2025, June 23). The PyMOL Molecular Graphics System. Available online: https://pymol.org."
},
{
"DOI": "10.1080/07391102.2023.2234031",
"article-title": "Conformational perturbation of SARS-CoV-2 spike protein using N-acetyl cysteine: An exploration of probable mechanism of action to combat COVID-19",
"author": "Debnath",
"doi-asserted-by": "crossref",
"first-page": "5042",
"journal-title": "J. Biomol. Struct. Dyn.",
"key": "ref_87",
"volume": "42",
"year": "2024"
},
{
"DOI": "10.3390/ijms232214049",
"doi-asserted-by": "crossref",
"key": "ref_88",
"unstructured": "Andrés, C.M.C., Pérez de la Lastra, J.M., Andrés Juan, C., Plou, F.J., and Pérez-Lebeña, E. (2022). Impact of Reactive Species on Amino Acids—Biological Relevance in Proteins and Induced Pathologies. Int. J. Mol. Sci., 23."
},
{
"DOI": "10.1128/JVI.00621-18",
"article-title": "Five Residues in the Apical Loop of the Respiratory Syncytial Virus Fusion Protein F2 Subunit Are Critical for Its Fusion Activity",
"author": "Hicks",
"doi-asserted-by": "crossref",
"first-page": "e00621-18",
"journal-title": "J. Virol.",
"key": "ref_89",
"volume": "92",
"year": "2018"
},
{
"DOI": "10.1128/JVI.00555-11",
"article-title": "Structure of Respiratory Syncytial Virus Fusion Glycoprotein in the Postfusion Conformation Reveals Preservation of Neutralizing Epitopes",
"author": "McLellan",
"doi-asserted-by": "crossref",
"first-page": "7788",
"journal-title": "J. Virol.",
"key": "ref_90",
"volume": "85",
"year": "2011"
},
{
"DOI": "10.1126/science.1234914",
"article-title": "Crystal Structure of Respiratory Syncytial Virus Fusion Glycoprotein Stabilized in the Prefusion Conformation by Human Antibody D25",
"author": "McLellan",
"doi-asserted-by": "crossref",
"first-page": "1113",
"journal-title": "Science",
"key": "ref_91",
"volume": "340",
"year": "2013"
},
{
"DOI": "10.1089/ars.2021.0033",
"article-title": "Influenza A Virus Hemagglutinin Is Produced in Different Disulfide-Bonded States",
"author": "Florido",
"doi-asserted-by": "crossref",
"first-page": "1081",
"journal-title": "Antioxid. Redox Signal.",
"key": "ref_92",
"volume": "35",
"year": "2021"
},
{
"DOI": "10.3390/aerobiology1020006",
"article-title": "Inactivation of Avian Influenza Virus Aerosol Using Membrane-Less Electrolyzed Water Spraying",
"author": "Yang",
"doi-asserted-by": "crossref",
"first-page": "70",
"journal-title": "Aerobiology",
"key": "ref_93",
"volume": "1",
"year": "2023"
},
{
"DOI": "10.1371/journal.pone.0261802",
"doi-asserted-by": "crossref",
"key": "ref_94",
"unstructured": "Urushidani, M., Kawayoshi, A., Kotaki, T., Saeki, K., Mori, Y., and Kameoka, M. (2022). Inactivation of SARS-CoV-2 and influenza A virus by dry fogging hypochlorous acid solution and hydrogen peroxide solution. PLoS ONE, 17."
},
{
"DOI": "10.5604/1232-1966.1108585",
"article-title": "Free chlorine loss during spraying of membraneless acidic electrolyzed water and its antimicrobial effect on airborne bacteria from poultry house",
"author": "Zhao",
"doi-asserted-by": "crossref",
"first-page": "249",
"journal-title": "Ann. Agric. Environ. Med.",
"key": "ref_95",
"volume": "21",
"year": "2014"
},
{
"DOI": "10.1111/cmi.12343",
"article-title": "Influenza virus replication in lung epithelial cells depends on redox-sensitive pathways activated by NOX4-derived ROS",
"author": "Amatore",
"doi-asserted-by": "crossref",
"first-page": "131",
"journal-title": "Cell. Microbiol.",
"key": "ref_96",
"volume": "17",
"year": "2015"
},
{
"DOI": "10.4315/0362-028X-62.8.857",
"article-title": "Inactivation of Escherichia coli O157:H7 and Listeria monocytogenes on Plastic Kitchen Cutting Boards by Electrolyzed Oxidizing Water",
"author": "Venkitanarayanan",
"doi-asserted-by": "crossref",
"first-page": "857",
"journal-title": "J. Food Prot.",
"key": "ref_97",
"volume": "62",
"year": "1999"
},
{
"DOI": "10.1007/s00595-014-1050-x",
"article-title": "Efficacy and safety of strong acid electrolyzed water for peritoneal lavage to prevent surgical site infection in patients with perforated appendicitis",
"author": "Kubota",
"doi-asserted-by": "crossref",
"first-page": "876",
"journal-title": "Surg. Today",
"key": "ref_98",
"volume": "45",
"year": "2015"
},
{
"article-title": "Intraabdominal Lavage of Hypochlorous Acid: A New Paradigm for the Septic and Open Abdomen",
"author": "Matthews",
"first-page": "107",
"journal-title": "Wounds",
"key": "ref_99",
"volume": "32",
"year": "2020"
},
{
"DOI": "10.3390/antibiotics8010013",
"doi-asserted-by": "crossref",
"key": "ref_100",
"unstructured": "Kampf, G. (2019). Antibiotic Resistance Can Be Enhanced in Gram-Positive Species by Some Biocidal Agents Used for Disinfection. Antibiotics, 8."
},
{
"DOI": "10.3390/cells13050441",
"doi-asserted-by": "crossref",
"key": "ref_101",
"unstructured": "Li, K., Deng, Z., Lei, C., Ding, X., Li, J., and Wang, C. (2024). The Role of Oxidative Stress in Tumorigenesis and Progression. Cells, 13."
},
{
"DOI": "10.1038/nrd4002",
"article-title": "Modulation of oxidative stress as an anticancer strategy",
"author": "Gorrini",
"doi-asserted-by": "crossref",
"first-page": "931",
"journal-title": "Nat. Rev. Drug Discov.",
"key": "ref_102",
"volume": "12",
"year": "2013"
},
{
"DOI": "10.1016/j.jinorgbio.2017.11.005",
"article-title": "HOCl and the control of oncogenesis",
"author": "Bauer",
"doi-asserted-by": "crossref",
"first-page": "10",
"journal-title": "J. Inorg. Biochem.",
"key": "ref_103",
"volume": "179",
"year": "2018"
},
{
"DOI": "10.1172/JCI70895",
"article-title": "Topical hypochlorite ameliorates NF-κB-mediated skin diseases in mice",
"author": "Leung",
"doi-asserted-by": "crossref",
"first-page": "5361",
"journal-title": "J. Clin. Investig.",
"key": "ref_104",
"volume": "123",
"year": "2013"
},
{
"key": "ref_105",
"unstructured": "Natarelli, N., Nong, Y., Maloh, J., and Sivamani, R. Hypochlorous Acid: Applications in Dermatology. J. Integr. Dermatol., Available online: https://jintegrativederm.org/article/view/93/17."
},
{
"DOI": "10.1016/j.redox.2021.102042",
"doi-asserted-by": "crossref",
"key": "ref_106",
"unstructured": "Jandova, J., Snell, J., Hua, A., Dickinson, S., Fimbres, J., and Wondrak, G.T. (2021). Topical hypochlorous acid (HOCl) blocks inflammatory gene expression and tumorigenic progression in UV-exposed SKH-1 high risk mouse skin. Redox Biol., 45."
},
{
"DOI": "10.3389/fonc.2022.887220",
"doi-asserted-by": "crossref",
"key": "ref_107",
"unstructured": "Snell, J.A., Jandova, J., and Wondrak, G.T. (2022). Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer. Front. Oncol., 12."
},
{
"DOI": "10.1186/s12903-023-02884-5",
"doi-asserted-by": "crossref",
"key": "ref_108",
"unstructured": "Zwicker, P., Freitag, M., Heidel, F.H., Kocher, T., and Kramer, A. (2023). Antiseptic efficacy of two mouth rinses in the oral cavity to identify a suitable rinsing solution in radiation- or chemotherapy induced mucositis. BMC Oral Health, 23."
},
{
"DOI": "10.1021/acsomega.1c05297",
"article-title": "Modifications of IL-6 by Hypochlorous Acids: Effects on Receptor Binding",
"author": "Robins",
"doi-asserted-by": "crossref",
"first-page": "35593",
"journal-title": "ACS Omega",
"key": "ref_109",
"volume": "6",
"year": "2021"
},
{
"DOI": "10.1002/jlb.58.6.667",
"article-title": "Taurine chloramine, a product of activated neutrophils, inhibits in vitro the generation of nitric oxide and other macrophage inflammatory mediators",
"author": "Marcinkiewicz",
"doi-asserted-by": "crossref",
"first-page": "667",
"journal-title": "J. Leukoc. Biol.",
"key": "ref_110",
"volume": "58",
"year": "1995"
},
{
"DOI": "10.1055/a-1467-5956",
"article-title": "A Concept for the Reduction of Mucosal SARS-CoV-2 Load using Hypochloric Acid Solutions",
"author": "Mueller",
"doi-asserted-by": "crossref",
"first-page": "348",
"journal-title": "Drug Res.",
"key": "ref_111",
"volume": "71",
"year": "2021"
},
{
"key": "ref_112",
"unstructured": "Mueller, C.A., Winter, M., Lippert, A., Hochauf-Stange, K., and Renner, B. (2024, April 24). Double-Blind, Randomised, Placebo-Controlled Study to Investigate the Efficacy of Nasal Spray and Mouth Wash Containing Hypochlorous Acid in SARS-CoV-2 Infected Patients; Deutsches Register Klinischer Studien (DRKS). Available online: https://drks.de/search/de/trial/DRKS00030721."
},
{
"key": "ref_113",
"unstructured": "The Committee on Efficacy Assessment of Disinfecting Substances Alternative to Alcohol for Use Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (2025, July 02). Final Report on Efficacy Assessment of Disinfecting Substances Alternative to Alcohol for Use Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Available online: https://www.nite.go.jp/data/000115863.pdf."
},
{
"DOI": "10.1128/AEM.02839-06",
"article-title": "Evaluation of liquid- and fog-based application of sterilox hypochlorous acid solution for surface inactivation of human norovirus",
"author": "Park",
"doi-asserted-by": "crossref",
"first-page": "4463",
"journal-title": "Appl. Environ. Microbiol.",
"key": "ref_114",
"volume": "73",
"year": "2007"
},
{
"DOI": "10.1186/s12903-022-02453-2",
"doi-asserted-by": "crossref",
"key": "ref_115",
"unstructured": "Aherne, O., Ortiz, R., Fazli, M.M., and Davies, J.R. (2022). Effects of stabilized hypochlorous acid on oral biofilm bacteria. BMC Oral Health, 22."
},
{
"DOI": "10.3390/microorganisms8081220",
"doi-asserted-by": "crossref",
"key": "ref_116",
"unstructured": "Nizer WSda, C., Inkovskiy, V., and Overhage, J. (2020). Surviving reactive chlorine stress: Responses of gram-negative bacteria to hypochlorous acid. Microorganisms, 8."
},
{
"DOI": "10.1016/j.jaci.2021.03.038",
"article-title": "C5aR inhibition of nonimmune cells suppresses inflammation and maintains epithelial integrity in SARS-CoV-2–infected primary human airway epithelia",
"author": "Posch",
"doi-asserted-by": "crossref",
"first-page": "2083",
"journal-title": "J. Allergy Clin. Immunol.",
"key": "ref_117",
"volume": "147",
"year": "2021"
},
{
"DOI": "10.3389/fimmu.2021.684014",
"doi-asserted-by": "crossref",
"key": "ref_118",
"unstructured": "Lafon, E., Diem, G., Witting, C., Zaderer, V., Bellmann-Weiler, R.M., Reindl, M., Bauer, A., Griesmacher, A., Fux, V., and Hoermann, G. (2021). Potent SARS-CoV-2-Specific T Cell Immunity and Low Anaphylatoxin Levels Correlate with Mild Disease Progression in COVID-19 Patients. Front. Immunol., 12."
},
{
"DOI": "10.1021/ja00486a025",
"article-title": "Mechanisms of chlorine oxidation of hydrogen peroxide",
"author": "Held",
"doi-asserted-by": "crossref",
"first-page": "5732",
"journal-title": "J. Am. Chem. Soc.",
"key": "ref_119",
"volume": "100",
"year": "1978"
},
{
"DOI": "10.1292/jvms.14-0413",
"article-title": "Evaluation of sprayed hypochlorous acid solutions for their virucidal activity against avian influenza virus through in vitro experiments",
"author": "Hakim",
"doi-asserted-by": "crossref",
"first-page": "211",
"journal-title": "J. Vet. Med. Sci.",
"key": "ref_120",
"volume": "77",
"year": "2015"
},
{
"DOI": "10.2500/ajra.2011.25.3545",
"article-title": "The Effect of a Low Concentration of Hypochlorous Acid on Rhinovirus Infection of Nasal Epithelial Cells",
"author": "Yu",
"doi-asserted-by": "crossref",
"first-page": "40",
"journal-title": "Am. J. Rhinol. Allergy",
"key": "ref_121",
"volume": "25",
"year": "2011"
},
{
"DOI": "10.1177/00220345231169434",
"article-title": "HOCl Rapidly Kills Corona, Flu, and Herpes to Prevent Aerosol Spread",
"author": "Guan",
"doi-asserted-by": "crossref",
"first-page": "1031",
"journal-title": "J. Dent. Res.",
"key": "ref_122",
"volume": "102",
"year": "2023"
},
{
"DOI": "10.1016/S2213-2600(22)00086-8",
"article-title": "Fast multiplex bacterial PCR of bronchoalveolar lavage for antibiotic stewardship in hospitalised patients with pneumonia at risk of Gram-negative bacterial infection (Flagship II): A multicentre, randomised controlled trial",
"author": "Darie",
"doi-asserted-by": "crossref",
"first-page": "877",
"journal-title": "Lancet Respir. Med.",
"key": "ref_123",
"volume": "10",
"year": "2022"
}
],
"reference-count": 123,
"references-count": 123,
"relation": {},
"resource": {
"primary": {
"URL": "https://www.mdpi.com/1999-4915/17/9/1219"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Hypochlorous Acid (HOCl) as a Promising Respiratory Antiseptic",
"type": "journal-article",
"update-policy": "https://doi.org/10.3390/mdpi_crossmark_policy",
"volume": "17"
}
