Oxoammonium salts exert antiviral effects against coronavirus via denaturation of their spike proteins.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 Oct 2024
13 Oct 2024
Historique:
received:
04
04
2024
accepted:
01
10
2024
medline:
14
10
2024
pubmed:
14
10
2024
entrez:
13
10
2024
Statut:
epublish
Résumé
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) infection has forced social changes worldwide. Development of potent antiviral agents is necessary to prevent future pandemics. Titanium oxide, a photocatalyst, is a long-acting antiviral agent; however, its effects are weakened in the dark. Therefore, new antiviral substances that can be used in the dark are needed. Two types of nitroxyl radicals, 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) and 2-azaadamantane N-oxyl (AZADO), are commonly used as oxidation catalysts utilizing oxygen in the air as the terminal oxidant. Therefore, in this study, we aimed to evaluate the potential of these radicals as antiviral compounds with sustained activity even in the dark. We evaluated the antiviral effects of oxoammonium salts corresponding to TEMPO and AZADO (TEMPO-Oxo and AZADO-Oxo, respectively), which are the active forms of nitroxyl radicals in oxidation reactions. TEMPO-Oxo and AZADO-Oxo inhibited the binding of SARS-CoV2 spike protein receptor-binding domain (S-RBD) to angiotensin-converting enzyme 2. Notably, AZADO-Oxo exhibited a 10-fold stronger inhibitory effect than TEMPO-Oxo. TEMPO-Oxo and AZADO-Oxo also denatured S-RBD; however, effects of AZADO-Oxo were 10-fold stronger than those of TEMPO-Oxo and did not change in the dark. Some S-RBD peptides treated with AZADO-Oxo were cleaved at the N-terminal side of tyrosine residues. TEMPO-Oxo and AZADO-Oxo exhibited concentration-dependent antiviral effects against feline coronavirus. In conclusion, active forms of the nitroxyl radicals, TEMPO-Oxo and AZADO-Oxo, exerted antiviral effects by denaturing S-RBD, regardless of the presence or absence of light, suggesting their potential as novel antiviral agents.
Identifiants
pubmed: 39397158
doi: 10.1038/s41598-024-75097-7
pii: 10.1038/s41598-024-75097-7
doi:
Substances chimiques
Antiviral Agents
0
Spike Glycoprotein, Coronavirus
0
Cyclic N-Oxides
0
TEMPO
VQN7359ICQ
spike protein, SARS-CoV-2
0
Nitrogen Oxides
0
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
nitroxyl
GFQ4MMS07W
Adamantane
PJY633525U
ACE2 protein, human
EC 3.4.17.23
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
23934Subventions
Organisme : Japan Society for the Promotion of Science
ID : 21H05210
Organisme : Japan Society for the Promotion of Science
ID : 22H02739
Informations de copyright
© 2024. The Author(s).
Références
Abdelrahman, Z., Li, M. & Wang, X. Comparative review of SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza a respiratory viruses. Front. Immunol. https://doi.org/10.3389/fimmu.2020.552909 (2020).
Foster, H. A., Ditta, I. B., Varghese, S. & Steele, A. Photocatalytic disinfection using titanium dioxide: Spectrum and mechanism of antimicrobial activity. Appl. Microbiol. Biotechnol. 90, 1847–1868 (2011). https://doi.org/10.1007/s00253-011-3213-7
Nakano, R. et al. Inactivation of various variant types of SARS-CoV-2 by indoor-light-sensitive TiO2-based photocatalyst. Sci. Rep. 12, 5804 (2022).
doi: 10.1038/s41598-022-09402-7
pubmed: 35422456
pmcid: 9010443
Iwabuchi, Y. Discovery and Exploitation of AZADO: The highly active Catalyst for Alcohol Oxidation. Chem. Pharm. Bull. (Tokyo). 61, 1197–1213 (2013).
doi: 10.1248/cpb.c13-00456
pubmed: 24292782
Sasano, Y. et al. Highly chemoselective aerobic oxidation of amino alcohols into amino carbonyl compounds. Angewandte Chemie-Int. Ed. 53, 3236–3240 (2014).
doi: 10.1002/anie.201309634
Hoover, J. M. & Stahl, S. S. Highly practical copper(I)/TEMPO catalyst system for chemoselective aerobic oxidation of primary alcohols. J. Am. Chem. Soc. 133, 16901–16910 (2011).
doi: 10.1021/ja206230h
pubmed: 21861488
pmcid: 3197761
Shibuya, M., Osada, Y., Sasano, Y., Tomizawa, M. & Iwabuchi, Y. Highly efficient, organocatalytic aerobic alcohol oxidation. J. Am. Chem. Soc. 133, 6497–6500 (2011).
doi: 10.1021/ja110940c
pubmed: 21473575
Seki, Y. et al. Serine-selective aerobic cleavage of peptides and a protein using a water-soluble copper-organoradical conjugate. Angewandte Chemie-Int. Ed. 53, 6501–6505 (2014).
doi: 10.1002/anie.201402618
Alexander, S. A., Kyi, C. & Schiesser, C. H. Nitroxides as anti-biofilm compounds for the treatment of Pseudomonas aeruginosa and mixed-culture biofilms. Org. Biomol. Chem. 13, 4751–4759 (2015).
doi: 10.1039/C5OB00284B
pubmed: 25804546
Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 181, 271–280e8 (2020).
doi: 10.1016/j.cell.2020.02.052
pubmed: 32142651
pmcid: 7102627
Tai, W. et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: Implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell. Mol. Immunol. 17, 613–620 (2020).
doi: 10.1038/s41423-020-0400-4
pubmed: 32203189
pmcid: 7091888
Yan, R. et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 367 (2020). https://www.science.org
Clausen, T. M. et al. SARS-CoV-2 infection depends on cellular heparan sulfate and ACE2. Cell. 183, 1043–1057.e15 (2020).
Kalra, R. S. & Kandimalla, R. Engaging the spikes: Heparan sulfate facilitates SARS-CoV-2 spike protein binding to ACE2 and potentiates viral infection. Signal Transduct. Targeted Therapy. 6. (2021). https://doi.org/10.1038/s41392-021-00470-1
Shibuya, M., Tomizawa, M., Suzuki, I. & Iwabuchi, Y. 2-Azaadamantane N-oxyl (AZADO) and 1-Me-AZADO: Highly efficient organocatalysts for oxidation of alcohols. J. Am. Chem. Soc. 128, 8412–8413 (2006).
doi: 10.1021/ja0620336
pubmed: 16802802
Jamison, D. A. et al. A comprehensive SARS-CoV-2 and COVID-19 review, Part 1: Intracellular overdrive for SARS-CoV-2 infection. Eur. J. Hum. Genet. 30, 889–898 (2022). https://doi.org/10.1038/s41431-022-01108-8
Ke, Z. et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature. 588, 498–502 (2020).
doi: 10.1038/s41586-020-2665-2
pubmed: 32805734
pmcid: 7116492
Sender, R. et al. The total number and mass of SARS-CoV-2 virions. https://doi.org/10.1073/pnas.2024815118/-/DCSupplemental
Lu, Y. et al. Inactivation of SARS-CoV-2 and photocatalytic degradation by TiO2 photocatalyst coatings. Sci. Rep. 12, (2022).
Palumbo, P., Prota, G. Isolation of a new intermediate in the oxidative conversion of 5,6-dihydroxyindole-2-carboxylic acid to melanin. Tetrahedron Lett. 28 (1987).
Nakagawa, S. et al. pH stability and antioxidant power of CycloDOPA and its derivatives. Molecules 23, (2018).
Tresnan, D. B., Levis, R., And & Holmes, K. V. Feline aminopeptidase N serves as a receptor for Feline, Canine, Porcine, and human coronaviruses in Serogroup I. J. Virol. 70 (1996). https://journals.asm.org/journal/jvi
Gozdziewska, M., Cichowicz, G., Markowska, K., Zawada, K. & Megiel, E. Nitroxide-coated silver nanoparticles: Synthesis, surface physicochemistry and antibacterial activity. RSC Adv. 5, 58403–58415 (2015).
doi: 10.1039/C5RA09366J
Hayashi, M., Shibuya, M. & Iwabuchi, Y. Oxidative conversion of silyl enol ethers to α,β-unsaturated ketones employing oxoammonium salts. Org. Lett. 14, 154–157 (2012).
doi: 10.1021/ol2029417
pubmed: 22181054
Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods. 9, 671–675 (2012). https://doi.org/10.1038/nmeth.2089