Electrolyzed hypochlorous acid water exhibits potent disinfectant activity against various viruses through irreversible protein aggregation

DOI record: { "DOI": "10.3389/fmicb.2023.1284274", "ISSN": [ "1664-302X" ], "URL": "http://dx.doi.org/10.3389/fmicb.2023.1284274", "abstract": "<jats:p>It is essential to employ efficient measures to prevent the transmission of pathogenic agents during a pandemic. One such method involves using hypochlorous acid (HClO) solution. The oxidative properties of HClO water (HAW) can contribute to its ability to eliminate viral particles. Here, we examined a highly purified slightly acidic hypochlorous acid water (Hp-SA-HAW) obtained from the reverse osmosis membrane treatment of an electrolytically-generated SA-HAW for its anti-viral activity and mode of action on viral proteins. Hp-SA-HAW exhibited broad-spectrum antiviral effects against various viruses, including adenovirus, hepatitis B virus, Japanese encephalitis virus (JEV), and rotavirus. Additionally, Hp-SA-HAW treatment dose-dependently resulted in irreversibly aggregated multimers of the JEV envelope and capsid proteins. However, Hp-SA-HAW treatment had no discernible effect on viral RNA, indicating that Hp-SA-HAW acts against amino acids rather than nucleic acids. Furthermore, Hp-SA-HAW substantially reduced the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including the ancestral variant and other multiple variants. Hp-SA-HAW treatment induced the aggregation of the SARS-CoV-2 spike and nuclear proteins and disrupted the binding of the purified spike protein of SARS-CoV-2 to human ACE2. This study demonstrates that the broad-spectrum virucidal activity of highly purified HClO is attributed to viral protein aggregation of virion via protein oxidation.</jats:p>", "alternative-id": [ "10.3389/fmicb.2023.1284274" ], "article-number": "1284274", "author": [ { "affiliation": [], "family": "Dianty", "given": "Rahmi", "sequence": "first" }, { "affiliation": [], "family": "Hirano", "given": "Junki", "sequence": "additional" }, { "affiliation": [], "family": "Anzai", "given": "Itsuki", "sequence": "additional" }, { "affiliation": [], "family": "Kanai", "given": "Yuta", "sequence": "additional" }, { "affiliation": [], "family": "Hayashi", "given": "Tsuyoshi", "sequence": "additional" }, { "affiliation": [], "family": "Morimoto", "given": "Masae", "sequence": "additional" }, { "affiliation": [], "family": "Kataoka-Nakamura", "given": "Chikako", "sequence": "additional" }, { "affiliation": [], "family": "Kobayashi", "given": "Sakura", "sequence": "additional" }, { "affiliation": [], "family": "Uemura", "given": "Kentaro", "sequence": "additional" }, { "affiliation": [], "family": "Ono", "given": "Chikako", "sequence": "additional" }, { "affiliation": [], "family": "Watanabe", "given": "Tokiko", "sequence": "additional" }, { "affiliation": [], "family": "Kobayashi", "given": "Takeshi", "sequence": "additional" }, { "affiliation": [], "family": "Murakami", "given": "Kosuke", "sequence": "additional" }, { "affiliation": [], "family": "Kikuchi", "given": "Kenji", "sequence": "additional" }, { "affiliation": [], "family": "Hotta", "given": "Kunimoto", "sequence": "additional" }, { "affiliation": [], "family": "Yoshikawa", "given": "Toshikazu", "sequence": "additional" }, { "affiliation": [], "family": "Taguwa", "given": "Shuhei", "sequence": "additional" }, { "affiliation": [], "family": "Matsuura", "given": "Yoshiharu", "sequence": "additional" } ], "container-title": "Frontiers in Microbiology", "container-title-short": "Front. Microbiol.", "content-domain": { "crossmark-restriction": true, "domain": [ "frontiersin.org" ] }, "created": { "date-parts": [ [ 2023, 10, 19 ] ], "date-time": "2023-10-19T07:39:40Z", "timestamp": 1697701180000 }, "deposited": { "date-parts": [ [ 2023, 10, 19 ] ], "date-time": "2023-10-19T07:39:45Z", "timestamp": 1697701185000 }, "indexed": { "date-parts": [ [ 2025, 10, 28 ] ], "date-time": "2025-10-28T15:17:29Z", "timestamp": 1761664649530, "version": "3.41.2" }, "is-referenced-by-count": 9, "issued": { "date-parts": [ [ 2023, 10, 19 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 10, 19 ] ], "date-time": "2023-10-19T00:00:00Z", "timestamp": 1697673600000 } } ], "link": [ { "URL": "https://www.frontiersin.org/articles/10.3389/fmicb.2023.1284274/full", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1965", "original-title": [], "prefix": "10.3389", "published": { "date-parts": [ [ 2023, 10, 19 ] ] }, "published-online": { "date-parts": [ [ 2023, 10, 19 ] ] }, "publisher": "Frontiers Media SA", "reference": [ { "DOI": "10.1073/pnas.78.1.210", "article-title": "Biological reactivity of hypochlorous acid: implications for microbicidal mechanisms of leukocyte myeloperoxidase", "author": "Albrich", "doi-asserted-by": "publisher", "first-page": "210", "journal-title": "Proc. Natl. Acad. Sci. U. S. A.", "key": "ref1", "volume": "78", "year": "1981" }, { "DOI": "10.1096/fasebj.5.3.1848195", "article-title": "Nucleotide chloramines and neutrophil-mediated cytotoxicity", "author": "Bernofsky", "doi-asserted-by": "publisher", "first-page": "295", "journal-title": "FASEB J.", "key": "ref2", "volume": "5", "year": "1991" }, { "DOI": "10.1016/j.joms.2020.06.029", "article-title": "Hypochlorous acid: A review", "author": "Block", "doi-asserted-by": "publisher", "first-page": "1461", "journal-title": "J. Oral Maxillofac. Surg.", "key": "ref3", "volume": "78", "year": "2020" }, { "DOI": "10.1126/science.325649", "article-title": "Australia antigen and the biology of hepatitis B", "author": "Blumberg", "doi-asserted-by": "publisher", "first-page": "17", "journal-title": "Science", "key": "ref4", "volume": "197", "year": "1977" }, { "DOI": "10.1128/JVI.00808-08", "article-title": "Development of reverse genetics systems for bluetongue virus: recovery of infectious virus from synthetic RNA transcripts", "author": "Boyce", "doi-asserted-by": "publisher", "first-page": "8339", "journal-title": "J. Virol.", "key": "ref5", "volume": "82", "year": "2008" }, { "DOI": "10.1038/s41579-022-00841-7", "article-title": "SARS-CoV-2 variant biology: immune escape, transmission and fitness", "author": "Carabelli", "doi-asserted-by": "publisher", "first-page": "162", "journal-title": "Nat. Rev. Microbiol.", "key": "ref6", "volume": "21", "year": "2023" }, { "DOI": "10.1080/13510002.1997.11747122", "article-title": "Modification of red cell membrane lipids by hypochlorous acid and haemolysis by preformed lipid chlorohydrins", "author": "Carr", "doi-asserted-by": "publisher", "first-page": "263", "journal-title": "Redox Rep.", "key": "ref7", "volume": "3", "year": "1997" }, { "DOI": "10.4049/jimmunol.126.4.1295", "article-title": "The myeloperoxidase-hydrogen peroxide-halide system as effector of neutrophil-mediated tumor cell cytotoxicity", "author": "Clark", "doi-asserted-by": "publisher", "first-page": "1295", "journal-title": "J. Immunol.", "key": "ref8", "volume": "126", "year": "1981" }, { "DOI": "10.1126/science.aaf5211", "article-title": "Replication of human noroviruses in stem cell-derived human enteroids", "author": "Ettayebi", "doi-asserted-by": "publisher", "first-page": "1387", "journal-title": "Science", "key": "ref9", "volume": "353", "year": "2016" }, { "DOI": "10.1016/j.antiviral.2020.104999", "article-title": "Ponesimod suppresses hepatitis B virus infection by inhibiting endosome maturation", "author": "Fauzyah", "doi-asserted-by": "publisher", "first-page": "104999", "journal-title": "Antiviral Res.", "key": "ref10", "volume": "186", "year": "2021" }, { "DOI": "10.4265/bio.11.147", "article-title": "Mechanisms of actions of sodium hypochlorite in cleaning and disinfection processes", "author": "Fukuzaki", "doi-asserted-by": "publisher", "first-page": "147", "journal-title": "Biocontrol Sci.", "key": "ref11", "volume": "11", "year": "2006" }, { "DOI": "10.1056/NEJMra031087", "article-title": "Hepatitis B virus infection--natural history and clinical consequences", "author": "Ganem", "doi-asserted-by": "publisher", "first-page": "1118", "journal-title": "N. Engl. J. Med.", "key": "ref12", "volume": "350", "year": "2004" }, { "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": "publisher", "first-page": "211", "journal-title": "J. Vet. Med. Sci.", "key": "ref13", "volume": "77", "year": "2015" }, { "DOI": "10.1039/a802949k", "article-title": "Reaction of HOCl with amino acids and peptides: EPR evidence for rapid rearrangement and fragmentation reactions of nitrogen-centred radicals", "author": "Hawkins", "doi-asserted-by": "publisher", "first-page": "1937", "journal-title": "J. Chem. Soc. Perkin Trans.", "key": "ref14", "volume": "2", "year": "1998" }, { "DOI": "10.1021/tx015548d", "article-title": "Hypochlorite-induced damage to DNA, RNA, and polynucleotides: formation of chloramines and nitrogen-centered radicals", "author": "Hawkins", "doi-asserted-by": "publisher", "first-page": "83", "journal-title": "Chem. Res. Toxicol.", "key": "ref15", "volume": "15", "year": "2002" }, { "DOI": "10.1021/tx050207b", "article-title": "Inactivation of protease inhibitors and lysozyme by hypochlorous acid: role of side-chain oxidation and protein unfolding in loss of biological function", "author": "Hawkins", "doi-asserted-by": "publisher", "first-page": "1600", "journal-title": "Chem. Res. Toxicol.", "key": "ref16", "volume": "18", "year": "2005" }, { "DOI": "10.1007/s00726-003-0016-x", "article-title": "Hypochlorite-induced oxidation of amino acids, peptides and proteins", "author": "Hawkins", "doi-asserted-by": "publisher", "first-page": "259", "journal-title": "Amino Acids", "key": "ref17", "volume": "25", "year": "2003" }, { "DOI": "10.1128/mSphere.00623-21", "article-title": "Dasabuvir inhibits human norovirus infection in human intestinal enteroids", "author": "Hayashi", "doi-asserted-by": "publisher", "first-page": "e0062321", "journal-title": "mSphere.", "key": "ref18", "volume": "6", "year": "2021" }, { "DOI": "10.1074/jbc.273.9.4997", "article-title": "Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to oxidize α-amino acids to a family of reactive aldehydes. Mechanistic studies identifying labile intermediates along the reaction pathway", "author": "Hazen", "doi-asserted-by": "publisher", "first-page": "4997", "journal-title": "J. Biol. Chem.", "key": "ref19", "volume": "273", "year": "1998" }, { "DOI": "10.3390/v9030056", "article-title": "Complete and incomplete hepatitis B virus particles: formation, function, and application", "author": "Hu", "doi-asserted-by": "publisher", "first-page": "56", "journal-title": "Viruses", "key": "ref20", "volume": "9", "year": "2017" }, { "DOI": "10.4265/bio.22.223", "article-title": "Stability of weakly acidic hypochlorous acid solution with microbicidal activity", "author": "Ishihara", "doi-asserted-by": "publisher", "first-page": "223", "journal-title": "Biocontrol Sci.", "key": "ref21", "volume": "22", "year": "2017" }, { "DOI": "10.1074/jbc.M304021200", "article-title": "5-Chlorouracil, a marker of DNA damage from hypochlorous acid during inflammation. A gas chromatography-mass spectrometry assay", "author": "Jiang", "doi-asserted-by": "publisher", "first-page": "32834", "journal-title": "J. Biol. Chem.", "key": "ref22", "volume": "278", "year": "2003" }, { "DOI": "10.1016/j.amjoto.2021.103264", "article-title": "Effect of hypochlorous acid nasal spray as an adjuvant therapy after functional endoscopic sinus surgery", "author": "Jiang", "doi-asserted-by": "publisher", "first-page": "103264", "journal-title": "Am. J. Otolaryngol.", "key": "ref23", "volume": "43", "year": "2022" }, { "article-title": "Catalysis or convenience? Perborate in context", "author": "John", "first-page": "217", "key": "ref24", "volume-title": "Advances in Inorganic Chemistry", "year": "2013" }, { "DOI": "10.1128/JCM.41.4.1548-1557.2003", "article-title": "Broadly reactive and highly sensitive assay for Norwalk-like viruses based on real-time quantitative reverse transcription-PCR", "author": "Kageyama", "doi-asserted-by": "publisher", "first-page": "1548", "journal-title": "J. Clin. Microbiol.", "key": "ref25", "volume": "41", "year": "2003" }, { "DOI": "10.1371/journal.ppat.1005455", "article-title": "Reverse genetics for Fusogenic bat-borne Orthoreovirus associated with acute respiratory tract infections in humans: role of outer capsid protein σC in viral replication and pathogenesis", "author": "Kawagishi", "doi-asserted-by": "publisher", "first-page": "e1005455", "journal-title": "PLoS Pathog.", "key": "ref26", "volume": "12", "year": "2016" }, { "DOI": "10.1093/jac/dkm498", "article-title": "Reduction of disinfectant bactericidal activities in clinically isolated Acinetobacter species in the presence of organic material", "author": "Kawamura-Sato", "doi-asserted-by": "publisher", "first-page": "568", "journal-title": "J. Antimicrob. Chemother.", "key": "ref27", "volume": "61", "year": "2008" }, { "DOI": "10.1126/science.169.3950.1095", "article-title": "Myeloperoxidase: contribution to the microbicidal activity of intact leukocytes", "author": "Klebanoff", "doi-asserted-by": "publisher", "first-page": "1095", "journal-title": "Science", "key": "ref28", "volume": "169", "year": "1970" }, { "DOI": "10.1128/JB.55.4.451-458.1948", "article-title": "The inhibition of sulfhydryl enzymes as the basis of the bactericidal action of chlorine", "author": "Knox", "doi-asserted-by": "publisher", "first-page": "451", "journal-title": "J. Bacteriol.", "key": "ref29", "volume": "55", "year": "1948" }, { "DOI": "10.3390/molecules25020378", "article-title": "Structural study on hypochlorous acid-mediated chlorination of betanin and its decarboxylated derivatives from an anti-inflammatory Beta vulgaris L. extract", "author": "Kumorkiewicz-Jamro", "doi-asserted-by": "publisher", "first-page": "378", "journal-title": "Molecules", "key": "ref30", "volume": "25", "year": "2020" }, { "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": "publisher", "first-page": "685", "journal-title": "Biochem. J.", "key": "ref31", "volume": "254", "year": "1988" }, { "DOI": "10.1016/j.virusres.2021.198383", "article-title": "Virucidal activity of slightly acidic hypochlorous acid water toward influenza virus and coronavirus with tests simulating practical usage", "author": "Miyaoka", "doi-asserted-by": "publisher", "first-page": "198383", "journal-title": "Virus Res.", "key": "ref32", "volume": "297", "year": "2021" }, { "DOI": "10.1292/jvms.22-0476", "article-title": "Isolation, molecular characterization, and disinfectants susceptibility of swine-carried mammalian orthoreoviruses in Japan in 2020-2022", "author": "Miyaoka", "doi-asserted-by": "publisher", "first-page": "185", "journal-title": "J. Vet. Med. Sci.", "key": "ref33", "volume": "85", "year": "2023" }, { "DOI": "10.1038/s41586-021-03944-y", "article-title": "SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion", "author": "Mlcochova", "doi-asserted-by": "publisher", "first-page": "114", "journal-title": "Nature", "key": "ref34", "volume": "599", "year": "2021" }, { "DOI": "10.1073/pnas.1910138117", "article-title": "Bile acids and ceramide overcome the entry restriction for GII.3 human norovirus replication in human intestinal enteroids", "author": "Murakami", "doi-asserted-by": "publisher", "first-page": "1700", "journal-title": "Proc. Natl. Acad. Sci. U. S. A.", "key": "ref35", "volume": "117", "year": "2020" }, { "key": "ref36", "year": "2023" }, { "DOI": "10.1371/journal.pone.0275488", "article-title": "Disinfection of otorhinolaryngological endoscopes with electrolyzed acid water: A cross-sectional and multicenter study", "author": "Okano", "doi-asserted-by": "publisher", "first-page": "e0275488", "journal-title": "PloS One", "key": "ref37", "volume": "17", "year": "2022" }, { "DOI": "10.1093/ofid/ofy210.984", "article-title": "A safer, more effective method for cleaning and disinfecting GI endoscopic procedure rooms", "author": "Overholt", "doi-asserted-by": "publisher", "first-page": "S346", "journal-title": "Open Forum Infect. Dis.", "key": "ref38", "volume": "5", "year": "2018" }, { "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": "publisher", "first-page": "4463", "journal-title": "Appl. Environ. Microbiol.", "key": "ref39", "volume": "73", "year": "2007" }, { "author": "Peacock", "key": "ref40", "year": "2021" }, { "DOI": "10.1007/s13671-013-0052-z", "article-title": "Topical hypochlorous acid (HOCl) as a potential treatment of pruritus", "author": "Pelgrift", "doi-asserted-by": "publisher", "first-page": "181", "journal-title": "Curr. Derm. Rep.", "key": "ref41", "volume": "2", "year": "2013" }, { "DOI": "10.1182/blood.V55.2.347.347", "article-title": "A potential role for hypochlorous acid in granulocyte-mediated tumor cell cytotoxicity", "author": "Slivka", "doi-asserted-by": "publisher", "first-page": "347", "journal-title": "Blood", "key": "ref42", "volume": "55", "year": "1980" }, { "DOI": "10.1016/j.abb.2009.10.006", "article-title": "Comparative study of HOCl-inflicted damage to bacterial DNA ex vivo and within cells", "author": "Suquet", "doi-asserted-by": "publisher", "first-page": "135", "journal-title": "Arch. Biochem. Biophys.", "key": "ref43", "volume": "493", "year": "2010" }, { "DOI": "10.1016/j.ijbiomac.2017.08.051", "article-title": "Hypochlorous acid induced structural and conformational modifications in human DNA: A multi-spectroscopic study", "author": "Tantry", "doi-asserted-by": "publisher", "first-page": "551", "journal-title": "Int. J. Biol. Macromol.", "key": "ref44", "volume": "106", "year": "2018" }, { "DOI": "10.1016/B978-0-12-420017-3.00005-0", "author": "Villamena", "doi-asserted-by": "crossref", "first-page": "13", "key": "ref45", "volume-title": "Chemistry of reactive species in reactive species detection in biology", "year": "2017" }, { "DOI": "10.1016/j.virol.2007.12.008", "article-title": "West Nile virus is neutralized by HOCl-modified human serum albumin that binds to domain III of the viral envelope protein E", "author": "Vossmann", "doi-asserted-by": "publisher", "first-page": "322", "journal-title": "Virology", "key": "ref46", "volume": "373", "year": "2008" }, { "article-title": "Hypochlorous acid as a potential wound care agent: part I. stabilized hypochlorous acid: A component of the inorganic armamentarium of innate immunity", "author": "Wang", "first-page": "e5", "journal-title": "J. Burns Wounds.", "key": "ref47", "volume": "6", "year": "2007" }, { "DOI": "10.1038/nchembio.85", "article-title": "Reconciling the chemistry and biology of reactive oxygen species", "author": "Winterbourn", "doi-asserted-by": "publisher", "first-page": "278", "journal-title": "Nat. Chem. Biol.", "key": "ref48", "volume": "4", "year": "2008" }, { "DOI": "10.1074/jbc.M605898200", "article-title": "Modeling the reactions of superoxide and myeloperoxidase in the neutrophil phagosome: implications for microbial killing", "author": "Winterbourn", "doi-asserted-by": "publisher", "first-page": "39860", "journal-title": "J. Biol. Chem.", "key": "ref49", "volume": "281", "year": "2006" }, { "DOI": "10.3390/pr9122240", "article-title": "Research trends on the application of electrolyzed water in food preservation and sanitation", "author": "Yan", "doi-asserted-by": "publisher", "first-page": "2240", "journal-title": "Processes", "key": "ref50", "volume": "9", "year": "2021" } ], "reference-count": 50, "references-count": 50, "relation": {}, "resource": { "primary": { "URL": "https://www.frontiersin.org/articles/10.3389/fmicb.2023.1284274/full" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Electrolyzed hypochlorous acid water exhibits potent disinfectant activity against various viruses through irreversible protein aggregation", "type": "journal-article", "update-policy": "https://doi.org/10.3389/crossmark-policy", "volume": "14" }