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

被引:11
作者
Lackner, Michaela [1 ]
Roessler, Annika [2 ]
Volland, Andre [2 ]
Stadtmueller, Marlena Nastassja [3 ]
Muellauer, Brigitte [2 ]
Banki, Zoltan [2 ]
Stroehle, Johannes [1 ]
Luttick, Angela [4 ]
Fenner, Jennifer [4 ]
Sarg, Bettina [5 ]
Kremser, Leopold [6 ]
Tone, Paul [6 ]
Stoiber, Heribert [2 ]
von Laer, Dorothee [2 ]
Wolff, Thorsten [3 ]
Schwarz, Carsten [7 ]
Nagl, Markus [1 ]
机构
[1] Med Univ Innsbruck, Inst Hyg & Med Microbiol, Schopfstr 41, A-6020 Innsbruck, Austria
[2] Med Univ Innsbruck, Inst Virol, Innsbruck, Austria
[3] Robert Koch Inst, Unit Influenza & Other Resp Viruses 17, Berlin, Germany
[4] 360Biolabs Pty Ltd, Melbourne, Vic, Australia
[5] Med Univ Innsbruck, Bioctr, Inst Med Biochem, Innsbruck, Austria
[6] Innovat Biomed Concepts Inc, Staten Isl, NY USA
[7] Pediat Clin Westbrandenburg, Div Cyst Fibrosis, CF Ctr Westbrandenburg, Potsdam, Germany
关键词
N-chlorotaurine; COVID-19; influenza; respiratory syncytial virus; antiviral; anti-infective; antiseptic; respiratory tract; TAURINE CHLORAMINE; HYPOCHLOROUS ACID; NVC-422; CHLORINATION; NEUTROPHILS; EFFICACY; THERAPY; SODIUM;
D O I
10.1080/22221751.2022.2065932
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 degrees 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.
引用
收藏
页码:1293 / 1307
页数:15
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