Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lackner, Michaela, Rössler, Annika, Volland, André, Stadtmüller, Marlena Nastassja, Müllauer, Brigitte, Banki, Zoltan, Ströhle, Johannes, Luttick, Angela, Fenner, Jennifer, Sarg, Bettina, Kremser, Leopold, Tone, Paul, Stoiber, Heribert, von Laer, Dorothee, Wolff, Thorsten, Schwarz, Carsten, Nagl, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132425/
https://www.ncbi.nlm.nih.gov/pubmed/35418279
http://dx.doi.org/10.1080/22221751.2022.2065932
Descripción
Sumario: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.