N-chlorotaurine is highly active against respiratory viruses including SARS-CoV-2 (COVID-19) in vitro

Abstract

N -chlorotaurine (NCT) a long-lived oxidant generated by leukocytes, can be synthesized chemically and applied topically as an anti-infective to different body sites, including the lung via inhalation. Here, we demonstrate the activity of NCT against viruses causing acute respiratory tract infections, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, and respiratory syncytial virus (RSV). Virucidal activity of NCT was tested in plaque assays, confirmed by RT-qPCR assays. Attack on virus proteins was investigated by mass spectrometry. NCT revealed broad virucidal activity against all viruses tested at 37°C and pH 7. A significant reduction in infectious particles of SARS-CoV-2 isolates from early 2020 by 1 log 10 was detected after 15 min of incubation in 1% NCT. Proteinaceous material simulating body fluids enhanced this activity by transchlorination mechanisms (1 −2 log 10 reduction within 1–10 min). Tested SARS-CoV-2 variants B.1.1.7 (Alpha) und B.1.351 (Beta) showed a similar susceptibility. Influenza virus infectious particles were reduced by 3 log 10 (H3N2) to 5 log 10 (H1N1pdm), RSV by 4 log 10 within a few min. Mass spectrometry of NCT-treated SARS-CoV-2 spike protein and 3C-like protease, influenza virus haemagglutinin and neuraminidase, and RSV fusion glycoprotein disclosed multiple sites of chlorination and oxidation as the molecular mechanism of action. Application of 1.0% NCT as a prophylactic and therapeutic strategy against acute viral respiratory tract infections deserves comprehensive clinical investigation.

Comparative Fungicidal Activities of N-Chlorotaurine and Conventional Antiseptics against Candida spp. Isolated from Vulvovaginal Candidiasis

“…According to the results of another study by our group [ 21 ] it was found that out of forty-four studied Candida strains, four (two C. glabrata , one C. albicans ) were characterized as susceptible dose-dependent, and two ( C. glabrata ) were found to be resistant to fluconazole. Due to the unspecific oxidizing/chlorinating mechanism of action of active chlorine compounds and confirmed previous studies against different kinds of pathogens, none of the studied Candida strains showed resistance to NCT [ 37 , 39 , 42 , 43 ]. Therefore, the use of NCT as an alternative antiseptic is also important in the treatment of VVC caused by fluconazole-resistant Candida strains.…”

Recombinant actin-depolymerizing factor of the apicomplexan Neospora caninum (NcADF) is susceptible to oxidation

“…However, interestingly, DTNB and bio-IAM methods showed that NCT was more efficient in producing cysteine oxidation compared to the same concentrations of H 2 O 2 . This difference can be explained by the specificity of NCT in oxidizing cysteine and methionine residues and chlorinating tyrosine, phenylalanine, histidine, and tryptophan ones and amino groups ( Peskin and Winterbourn, 2001 ; Eitzinger et al., 2012 ; Lackner et al., 2022 ), while H 2 O 2 has a broad and unspecific effect ( Fligiel et al., 1984 ). Cofilin 1 cysteine residues are susceptible to oxidation by NCT and H 2 O 2 ( Klemke et al., 2008 ; Klamt et al., 2009 ; Luo et al., 2014 ; Cameron et al., 2015 ).…”

“…NCT is a chlorinated amino acid derived from taurine, that is naturally produced by human leucocytes and has antiseptic properties (Gottardi and Nagl, 2010). Additionally, NCT has a limited spectrum of reactivity targeting most cysteine and methionine residues, aromatic amino acids, and amino groups of the proteins (Peskin and Winterbourn, 2001;Eitzinger et al, 2012;Lackner et al, 2022). In contrast, a similar mechanism induced by H 2 O 2 usually damages proteins (Fligiel et al, 1984) and other biomolecules.…”

Antimicrobial efficacy, mode of action and in vivo use of hypochlorous acid (HOCl) for prevention or therapeutic support of infections

“…HOCl and NCT have anti-inflammatory properties which lead to reduced local inflammation, lower infectivity through reduced permeability, and perhaps lower morbidity and mortality overall [ 48 ], [ 49 ]. The verified unique stability and low-level reactivity of NCT are considered essential for both its function in the mammalian defense system and its practical applicability, which manifests itself in an optimal compromise between microbiocidal activity and toxicity [ 50 ], [ 51 ].…”