Abstract
Coating high-touch surfaces with inorganic agents, such as metals, appears to be a promising long-term disinfection strategy. However, there is a lack of studies exploring the effectiveness of copper-based products against viruses. In this study, we evaluated the cytotoxicity and virucidal effectiveness of products and materials containing copper against mouse hepatitis virus (MHV-3), a surrogate model for SARS-CoV-2. The results demonstrate that pure CuO and Cu possess activity against the enveloped virus at very low concentrations, ranging from 0.001 to 0.1% (w/v). A greater virucidal efficacy of CuO was found for nanoparticles, which showed activity even against viruses that are more resistant to disinfection such as feline calicivirus (FCV). Most of the evaluated products, with concentrations of Cu or CuO between 0.003 and 15% (w/v), were effective against MHV-3. Cryomicroscopy images of an MHV-3 sample exposed to a CuO-containing surface showed extensive damage to the viral capsid, presumably due to the direct or indirect action of copper ions.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The authors declare that the data supporting the findings of this study are available within the paper and itssupplementary Information files. Should any raw data files be needed in another format they are available from the corresponding author upon request.
References
Andrade AC, Campolina-Silva GH, Queiroz-Junior CM, de Oliveira LC, Lacerda LD, Gaggino JC, de Souza FR, de Meira CI, Passos IB, Teixeira DC, Bittencourt-Silva PG (2021) A biosafety level 2 mouse model for studying betacoronavirus-induced acute lung damage and systemic manifestations. J Virol 95(22):10–128. https://doi.org/10.1128/jvi.01276-21
Baer DR, Artyushkova K, Richard Brundle C, Castle JE, Engelhard MH, Gaskell KJ et al (2019) Practical guides for X-ray photoelectron spectroscopy: first steps in planning, conducting, and reporting XPS measurements. J Vac Sci Technol 37(3):03140. https://doi.org/10.1116/1.5065501
Baker M, Assis SL, Grilli R, Costa I (2008) Investigation of the electrochemical behavior and surface chemistry of a Ti-13Nb-13Zr alloy exposed in MEM cell culture media with and without the addition of H2O2. Surf Interface Anal 40(3–4):220–224. https://doi.org/10.1002/sia.2616
Baker MA, Assis SL, Higa OZ, Costa I (2009) Nanocomposite hydroxyapatite formation on a Ti–13Nb–13Zr alloy exposed in a MEM cell culture medium and the effect of H2O2 addition. Acta Biomater 5(1):63–75. https://doi.org/10.1016/j.actbio.2008.08.008
Beamson D, Briggs G (1993) High-resolution XPS of organic polymers, the scienta ESCA300 database. ADMA 5(10):778–778. https://doi.org/10.1002/adma.19930051035
Behzadinasab S, Chin A, Hosseini M, Poon L, Ducker WA (2020) A surface coating that rapidly inactivates SARS-CoV-2. ACS Appl Mater Interfaces 12(31):34723–34727. https://doi.org/10.1021/acsami.0c11425
Beppu MM, Arns CW, Neto JBMR, Bataglioli, Garcia AB, Lopes LA, Calais GB, inventors; Universidade Estadual de Campinas (UNICAMP) assignee (2022) Processo de funcionalização antiviral de superfícies. BR patente. 10 2020 020907 8 A2, 2022 Apr 26
Borkow G (2012) Safety of using copper oxide in medical devices and consumer products. Curr Chem Biol 6(1):86–92. https://doi.org/10.2174/187231312799984349
Borkow G, Gabbay J (2004) Putting copper into action: copper-impregnated products with potent biocidal activities. FASEB J 18(14):1728–1730. https://doi.org/10.1096/fj.04-2029fje
Borkow G, Zhou SS, Page T, Gabbay J (2010a) A novel anti-influenza copper oxide containing respiratory face mask. PLoS ONE 5(6):e11295. https://doi.org/10.1371/journal.pone.0011295
Borkow G, Okon-Levy N, Gabbay J (2010b) Copper oxide impregnated wound dressing: biocidal and safety studies. Wounds 22(12):301–310
British Standards Institute. BS EN 14476:2013+A2:2019 Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of virucidal activity in the medical area. Test method and requirements (Phase 2/Step 1). https://www.en-standard.eu/bs-en-14476-2013-a2-2019-chemical-disinfectants-and-antiseptics-quantitative-suspension-test-for-the-evaluation-of-virucidal-activity-in-the-medical-area-test-method-and-requirements-phase-2-step-1/
British Standards Institute (2019) BS ISO 21702:2019. Measurement of antiviral activity on plastics and other non-porous surfaces. https://www.iso.org/standard/71365.html
British Standards Institute. BS ISO 18184:2019 Textiles — Determination of the antiviral activity of textile products. https://www.en-standard.eu/bs-iso-18184-2019-textiles-determination-of-antiviral-activity-of-textile-products/
Castro ÍB, Westphal E, Fillmann G (2011) Tintas anti-incrustantes de terceira geração: novos biocidas no ambiente aquático. Quim Nova 34(6):1021–1031. https://doi.org/10.1590/S0100-40422011000600020
Centers for Disease Control and Prevention (CDC) (2020) Implementing filtering facepiece respirator (FFR) reuse, including reuse after decontamination, when there are known shortages of N95 respirators
CDC (2021) FOR IMMUNIZATION, National Center et al. Science Brief: SARS-CoV-2 and Surface (Fomite) Transmission for Indoor Community Environments. In: CDC COVID-19 Science Briefs. Centers for Disease Control and Prevention (US)
Chandrasekar R, Rao S, Lavu V, Kumar K (2015) Evaluation of antimicrobial properties of bioactive glass used in regenerative periodontal therapy. J Indian Soc Periodontol 19(5):516. https://doi.org/10.4103/0972-124X.167166
Dellanno C, Vega Q, Boesenberg D (2009) The antiviral action of common household disinfectants and antiseptics against murine hepatitis virus, a potential surrogate for SARS coronavirus. Am J Infect Control 37(8):649–652. https://doi.org/10.1016/j.ajic.2009.03.012
EPA (2009) Reregistration Eligibility Decision (RED) for Coppers. https://www3.epa.gov/pesticides/chem_search/reg_actions/reregistration/red_G-26_26-May-09.pdf
Fujimori Y et al (2012) Novel antiviral characteristics of nanosized copper (I) iodide particles showing inactivation activity against 2009 pandemic H1N1 influenza virus. Appl Environ Microbiol 78(4):951–955. https://doi.org/10.1128/AEM.06284-11
Gabbay J, Borkow G, Mishal J, Magen E, Zatcoff R, Shemer-Avni Y (2006) Copper oxide impregnated textiles with potent biocidal activities. J Ind Text 35(4):323–335. https://doi.org/10.1177/1528083706060785
Garcia AB et al (2021) Coding-complete genome sequence of murine hepatitis virus strain 3 from Brazil. Microbiol Resourc Announce 10(15):e00248-e321. https://doi.org/10.1128/MRA.00248-21
Henson TE, Navratilova J, Tennant AH, Bradham KD, Rogers KR, Hughes MF (2019) In vitro intestinal toxicity of copper oxide nanoparticles in rat and human cell models. Nanotoxicology 13(6):795–811. https://doi.org/10.1080/17435390.2019.1578428
Hosseini M, Chin AWH, Behzadinasab AS, Poon LLM, Ducker WA (2021) Cupric oxide coating that rapidly reduces infection by SARS-CoV-2 via solids. ACS Appl Mater Interfaces 13(5):5919–5928. https://doi.org/10.1021/acsami.0c19465
Jensen KA et al (2011) Towards a method for detecting the potential genotoxicity of nanomaterials. Deliverable 3. Final protocol for producing suitable manufactured nanomaterial exposure media. The generic NANOGENOTOX Dispersion Protocol. Standard Operating Procedure (SOP) and Background Documentation. 2011, pp. 1–33. https://www.anses.fr/en/system/files/nanogenotox_deliverable_5.pdf
Keller AA, Adeleye AS, Conway JR, Garner KL, Zhao L, Cherr GN et al (2017) Comparative environmental fate and toxicity of copper nanomaterials. NanoImpact 7:28–40. https://doi.org/10.1016/j.impact.2017.05.003)
Körner RW, Majjouti M, Alcazar M, Mahabir E (2020) Of mice and men: the coronavirus MHV and mouse models as a translational approach to understand SARS-CoV-2. Viruses 12(8):880. https://doi.org/10.3390/v12080880
Lei C, Yang J, Hu J, Sun X (2020) On the calculation of TCID50 for quantitation of virus infectivity. Virol Sin 36(1):141–144. https://doi.org/10.1007/s12250-020-00230-5
Lin Q, Lim JYC, Xue K, Yew PYM, Owh C, Chee PL et al (2020) Sanitizing agents for virus inactivation and disinfection. View. https://doi.org/10.1002/viw2.16
Lin N, Verma D, Saini N, Arbi R, Munir M, Jovic M et al (2021) Antiviral nanoparticles for sanitizing surfaces: a roadmap to self-sterilizing against COVID-19. Nano Today 40:101267. https://doi.org/10.1016/j.nantod.2021.101267
Lopes ESN et al (2023) inventors; UNICAMP assignee. Processo de obtenção de composição com atividade virucida, composição com atividade virucida e uso. BR patent 102021024697-9, 2023 Jun 20. https://busca.inpi.gov.br/pePI/servlet/PatenteServletController?Action=detail&CodPedido=1638381&SearchParameter=BR102021024697-9%20
Lopes ESN, Gabriel LP, Arns CW, Silva TBB, Moraes AP, Jacinto GS, inventors (2023) Universidade Estadual de Campinas (UNICAMP) assignee. Processo de obtenção de composição com atividade virucida, composição com atividade virucida e uso. BR patent 102021024697-9, 2023 Jun 20
Mantlo E, Rhodes T, Boutros J, Patterson-Fortin L, Evans A, Paessler S (2020) In vitro efficacy of a copper iodine complex PPE disinfectant for SARS-CoV-2 inactivation. F1000Research 9:674. https://doi.org/10.12688/f1000research.24651.2
Meiksin A (2020) Dynamics of COVID-19 transmission including indirect transmission mechanisms: a mathematical analysis. Epidemiol Infect. https://doi.org/10.1017/s0950268820002563
Microchem Laboratory. Log and percent reductions in microbiology and antimicrobial testing. https://microchemlab.com/information/log-and-percent-reductions-microbiology-and-antimicrobial-testing/
Mochida K, Fujii K (2009) Further effects of alternative biocides on aquatic organisms. In: Arai T, Harino H, Ohji M, Langston W (eds) Ecotoxicology of antifouling biocides. Springer, Tokyo
Montero DA, Arellano C, Pardo M, Vera R, Gálvez R, Cifuentes M et al (2019) Antimicrobial properties of a novel copper-based composite coating with potential for use in healthcare facilities. Antimicrob Resist Infect Control. https://doi.org/10.1186/s13756-018-0456-4
NIBIB (2009) U.S National Institute of Biomedical Imaging and Bioengineering, 2009. https://www.nibib.nih.gov/science-education/science-topics/biomaterials
Nickels L (2020) Antiviral boost for nanoparticles. Met Powder Rep 75(6):330–333. https://doi.org/10.1016/j.mprp.2020.10.002
Pan C, Phadke KS, Li Z, Ouyang G, Kim TH, Zhou L et al (2022) Sprayable copper and copper–zinc nanowires inks for antiviral surface coating. RSC Adv 12(10):6093–6098. https://doi.org/10.1039/D1RA08755J
Purniawan A, Lusida MI, Pujiyanto RW, Nastri AM, Permanasari AA, Harsono AAH et al (2022) Synthesis and assessment of copper-based nanoparticles as a surface coating agent for antiviral properties against SARS-CoV-2. Sci Rep 12(1):4835
Ramos-Zúñiga J, Bruna N, Pérez-Donoso JM (2023) Toxicity mechanisms of copper nanoparticles and copper surfaces on bacterial cells and viruses. Int J Mol Sci 24(13):10503–10513. https://doi.org/10.3390/ijms241310503
Rakowska PD, Tiddia M, Faruqui N, Bankier C, Pei Y, Pollard AJ, Zhang J, Gilmore IS (2021) Antiviral surfaces and coatings and their mechanisms of action. Commun Mater 2(1):1–19. https://doi.org/10.1038/s43246-021-00153-y
Reinosa JJ, Enríquez E, Fuertes V, Liu S, Menéndez J, Fernández JF (2022) The challenge of antimicrobial glazed ceramic surfaces. Ceram Int 48(6):7393–7404. https://doi.org/10.1016/j.ceramint.2021.12.121
Shard AG (2014) Detection limits in XPS for more than 6000 binary systems using Al and Mg Kα X-rays. Surf Interface Anal 46(3):175–185. https://doi.org/10.1002/sia.5406
Shchukarev A, Malekzadeh BÖ, Ransjö M, Tengvall P, Westerlund A (2017) Surface characterization of insulin-coated Ti6Al4V medical implants conditioned in cell culture medium: an XPS study. J Electron Spectrosc Relat Phenom 1(216):33–38. https://doi.org/10.1016/j.elspec.2017.03.001
Singh AV, Kayal A, Malik A, Maharjan RS, Dietrich P, Thissen A, Siewert K, Curato C, Pande K, Prahlad D, Kulkarni N (2022) Interfacial water in the SARS spike protein: investigating the interaction with human ACE2 receptor and in vitro uptake in A549 cells. Langmuir 38(26):7976–7988. https://doi.org/10.1021/acs.langmuir.2c00671
Van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, Tamin A, Harcourt JL, Thornburg NJ, Gerber SI, Lloyd-Smith JO, de Wit E, Munster VJ (2020) Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med 382(16):1564–1567. https://doi.org/10.1056/nejmc2004973
WHO (2020) World Health Organization. Cleaning and disinfection of environmental surfaces in the context of COVID-19: interim guidance. who.int/publications. May 15, 2020. https://www.who.int/publications/i/item/cleaning-and-disinfection-of-environmental-surfaces-inthe-context-of-covid-19
Yaniv Z, Mao D, Avent J, Li X, Rao MKK, Castro S, Upadhyaya A, K. Nano, inventors; Magic Holdings Inc, assignee (2015) Disinfectant spray comprising copper iodide. US patent 9615572
Zatcoff RC, Smith MS, Borkow G (2008) Treatment of tinea pedis with socks containing copper-oxide-impregnated fibers. Foot 18(3):136–141. https://doi.org/10.1016/j.foot.2008.03.005
Acknowledgements
This study was financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. The authors would like to thank the Faculty of Mechanical Engineering at UNICAMP for granting part of the analyzed samples and to LNNano/CNPEM for access to the Electron Microscopy Spectroscopy and Light Scattering facility and technical support, in the execution of the proposals TEM-27833F and XPS-20220417. FAPESP – CeRTEV Grant No. 2013/07793-6.
Funding
GSJ and APM were supported by CAPES and JT by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico). CWA is a CNPq research fellow. LFGD, MTS and PNLF are supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo).
Author information
Authors and Affiliations
Contributions
GSJ: Performed the daily maintenance of cells and viruses for in vitro assays, performed assays for analysis of cytotoxicity and virucidal activity, characterized materials via interpretation of XPS spectra and wrote and submitted this article. LFGD: Assisted in the characterization of the materials, performing the deconvolution of the XPS spectra with Gaussian/Lorentzian functions in the CasaXPS software, in addition to assisting in the interpretation of the spectra. JT: assisted in the cytotoxicity and virucidal activity assays, in the submission of a proposal for physical–chemical analysis (XPS) via CNPEM and in the survey of the theoretical reference. PNLF: Assisted in the characterization of materials (XPS). MTS: Assisted in the acquisition and characterization of samples and interpretation of results. APM: Assisted in cytotoxicity assays (MTT). CWA: Assisted in designing the research proposal, submitting a proposal for XPS analysis, and acquiring samples and materials. Note: All authors reviewed the manuscript.
Corresponding author
Ethics declarations
Competing Interests
MTS was the executive director of Vetra Ltda., a company that detents the license of F18 and that was solely the material provider. The remaining authors have no conflicts of interest to declare.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Jacinto, G.S., Dias, L.F.G., Tsukamoto, J. et al. Insight into the role of copper-based materials against the coronaviruses MHV-3, a model for SARS-CoV-2, during the COVID-19 pandemic. Biometals (2024). https://doi.org/10.1007/s10534-024-00585-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10534-024-00585-2