|
1
|
Kusior A, Mazurkow J, Jelen P, Bik M, Raza S, Wdowiak M, Nikiforov K, Paczesny J. Copper Oxide Electrochemical Deposition to Create Antiviral and Antibacterial Nanocoatings. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2024; 40:14838-14846. [PMID: 38978473 PMCID: PMC11270987 DOI: 10.1021/acs.langmuir.4c00642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 06/07/2024] [Accepted: 07/02/2024] [Indexed: 07/10/2024]
Abstract
The impact of the reaction environment on the formation of the polycrystalline layer and its biomedical (antimicrobial) applications were analyzed in detail. Copper oxide layers were synthesized using an electrodeposition technique, with varying additives influencing the morphology, thickness, and chemical composition. Scanning electron microscopy (SEM) images confirmed the successful formation of polyhedral structures. Unmodified samples (CuL) crystallized as a mixture of copper oxide (I) and (II), with a thickness of approximately 1.74 μm. The inclusion of the nonconductive polymer polyvinylpyrrolidone (PVP) during synthesis led to a regular and compact CuO-rich structure (CuL-PVP). Conversely, adding glucose resulted in forming a Cu2O-rich nanostructured layer (CuL-D(+)G). Both additives significantly reduced the sample thickness to 617 nm for CuL-PVP and 560 nm for CuL-D(+)G. The effectiveness of the synthesized copper oxide layers was demonstrated in their ability to significantly reduce the T4 phage titer by approximately 2.5-3 log. Notably, CuL-PVP and CuL-D(+)G showed a more substantial reduction in the MS2 phage titer, achieving about a 5-log decrease. In terms of antibacterial activity, CuL and CuL-PVP exhibited moderate efficacy against Escherichia coli, whereas CuL-D(+)G reduced the E. coli titer to undetectable levels. All samples induced similar reductions in Staphylococcus aureus titer. The study revealed differential susceptibilities, with Gram-negative bacteria being more vulnerable to CuL-D(+)G due to its unique composition and morphology. The antimicrobial properties were attributed to the redox cycling of Cu ions, which generate ROS, and the mechanical damage caused by nanostructured surfaces. A crucial finding was the impact of surface composition rather than surface morphology on antimicrobial efficacy. Samples with a dominant Cu2O composition exhibited potent antibacterial and antiviral properties, whereas CuO-rich materials showed predominantly enhanced antiviral activity. This research highlights the significance of phase composition in determining the antimicrobial properties of copper oxide layers synthesized through electrodeposition.
Collapse
Affiliation(s)
- Anna Kusior
- AGH
University of Krakow, Faculty of Material
Sciences and Ceramics, Mickiewicza 30, Kraków 30-059, Poland
| | - Julia Mazurkow
- AGH
University of Krakow, Faculty of Material
Sciences and Ceramics, Mickiewicza 30, Kraków 30-059, Poland
| | - Piotr Jelen
- AGH
University of Krakow, Faculty of Material
Sciences and Ceramics, Mickiewicza 30, Kraków 30-059, Poland
| | - Maciej Bik
- AGH
University of Krakow, Faculty of Material
Sciences and Ceramics, Mickiewicza 30, Kraków 30-059, Poland
| | - Sada Raza
- Institute
of Physical Chemistry, Polish Academy of
Sciences, Kasprzaka 44/52, Warszawa 01-224, Poland
| | - Mateusz Wdowiak
- Institute
of Physical Chemistry, Polish Academy of
Sciences, Kasprzaka 44/52, Warszawa 01-224, Poland
| | - Kostyantyn Nikiforov
- Institute
of Physical Chemistry, Polish Academy of
Sciences, Kasprzaka 44/52, Warszawa 01-224, Poland
| | - Jan Paczesny
- Institute
of Physical Chemistry, Polish Academy of
Sciences, Kasprzaka 44/52, Warszawa 01-224, Poland
| |
Collapse
|
|
2
|
Albalawi SA, Albalawi RA, Albalawi AA, Alanazi RF, Almahlawi RM, Alhwity BS, Alatawi BD, Elsherbiny N, Alqifari SF, Abdel-Maksoud MS. The Possible Mechanisms of Cu and Zn in the Treatment and Prevention of HIV and COVID-19 Viral Infection. Biol Trace Elem Res 2024; 202:1524-1538. [PMID: 37608131 DOI: 10.1007/s12011-023-03788-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 07/18/2023] [Indexed: 08/24/2023]
Abstract
Due to their unique properties and their potential therapeutic and prophylactic applications, heavy metals have attracted the interest of many researchers, especially during the outbreak of COVID-19. Indeed, zinc (Zn) and copper (Cu) have been widely used during viral infections. Zn has been reported to prevent excessive inflammatory response and cytokine storm, improve the response of the virus to Type I interferon (IFN-1), and enhance the production of IFN-a to counteract the antagonistic effect of SARS-CoV-2 virus protein on IFN. Additionally, Zn has been found to promote the proliferation and differentiation of T and B lymphocytes, thereby improving immune function, inhibiting RNA-dependent RNA polymerase (RdRp) in SARS- CoV-2 reducing the viral replication and stabilizing the cell membrane by preventing the proteolytic processing of viral polyprotein and proteases enzymes. Interestingly, Zn deficiency has been correlated with enhanced SARS-CoV-2 viral entry through interaction between the ACE2 receptor and viral spike protein. Along with zinc, Cu possesses strong virucidal capabilities and is known to be effective at neutralizing a variety of infectious viruses, including the poliovirus, influenza virus, HIV type 1, and other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Cu-related antiviral action has been linked to different pathways. First, it may result in permanent damage to the viral membrane, envelopes, and genetic material of viruses. Second, Cu produces reactive oxygen species to take advantage of the redox signaling mechanism to eradicate the virus. The present review focused on Zn and Cu in the treatment and prevention of viral infection. Moreover, the application of metals such as Cu and gold in nanotechnology for the development of antiviral therapies and vaccines has been also discussed.
Collapse
Affiliation(s)
- Shatha A Albalawi
- Pharm D program, Faculty of pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Raneem A Albalawi
- Pharm D program, Faculty of pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Amaal A Albalawi
- Pharm D program, Faculty of pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Raghad F Alanazi
- Pharm D program, Faculty of pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Raghad M Almahlawi
- Pharm D program, Faculty of pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Basma S Alhwity
- Pharm D program, Faculty of pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Bashayer D Alatawi
- Pharm D program, Faculty of pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Nehal Elsherbiny
- Department of Pharmaceutical chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
| | - Saleh F Alqifari
- Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Mohamed S Abdel-Maksoud
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| |
Collapse
|
|
3
|
Hadinejad F, Morad H, Jahanshahi M, Zarrabi A, Pazoki-Toroudi H, Mostafavi E. A Novel Vision of Reinforcing Nanofibrous Masks with Metal Nanoparticles: Antiviral Mechanisms Investigation. ADVANCED FIBER MATERIALS 2023; 5:1-45. [PMID: 37361103 PMCID: PMC10088653 DOI: 10.1007/s42765-023-00275-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 02/13/2023] [Indexed: 06/28/2023]
Abstract
Prevention of spreading viral respiratory disease, especially in case of a pandemic such as coronavirus disease of 2019 (COVID-19), has been proved impossible without considering obligatory face mask-wearing protocols for both healthy and contaminated populations. The widespread application of face masks for long hours and almost everywhere increases the risks of bacterial growth in the warm and humid environment inside the mask. On the other hand, in the absence of antiviral agents on the surface of the mask, the virus may have a chance to stay alive and be carried to different places or even put the wearers at risk of contamination when touching or disposing the masks. In this article, the antiviral activity and mechanism of action of some of the potent metal and metal oxide nanoparticles in the role of promising virucidal agents have been reviewed, and incorporation of them in an electrospun nanofibrous structure has been considered an applicable method for the fabrication of innovative respiratory protecting materials with upgraded safety levels. Graphical Abstract
Collapse
Affiliation(s)
- Farinaz Hadinejad
- Nanotechnology Research Institute, Faculty of Chemical Engineering, Babol Noushirvani University of Technology, Babol, 4714873113 Iran
| | - Hamed Morad
- Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, 1475886973 Iran
- Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, 4691710001 Iran
| | - Mohsen Jahanshahi
- Nanotechnology Research Institute, Faculty of Chemical Engineering, Babol Noushirvani University of Technology, Babol, 4714873113 Iran
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34396 Turkey
| | - Hamidreza Pazoki-Toroudi
- Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, 1449614535 Iran
- Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, 1449614535 Iran
| | - Ebrahim Mostafavi
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305 USA
- Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305 USA
| |
Collapse
|
|
4
|
Bahrami A, Arabestani MR, Taheri M, Farmany A, Norozzadeh F, Hosseini SM, Nozari H, Nouri F. Exploring the Role of Heavy Metals and Their Derivatives on the Pathophysiology of COVID-19. Biol Trace Elem Res 2022; 200:2639-2650. [PMID: 34448983 PMCID: PMC8391869 DOI: 10.1007/s12011-021-02893-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 08/17/2021] [Indexed: 12/13/2022]
Abstract
Many aspects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease, COVID-19, have been studied to determine its properties, transmission mechanisms, and pathology. These efforts are aimed at identifying potential approaches to control or treat the disease. Early treatment of novel SARS-CoV-2 infection to minimize symptom progression has minimal evidence; however, many researchers and firms are working on vaccines, and only a few vaccines exist. COVID-19 is affected by several heavy metals and their nanoparticles. We investigated the effects of heavy metals and heavy metal nanoparticles on SARS-CoV-2 and their roles in COVID-19 pathogenesis. AgNPs, AuNPs, gold-silver hybrid NPs, copper nanoparticles, zinc oxide, vanadium, gallium, bismuth, titanium, palladium, silver grafted graphene oxide, and some quantum dots were tested to see if they could minimize the severity or duration of symptoms in patients with SARS-CoV-2 infection when compared to standard therapy.
Collapse
Affiliation(s)
- Ali Bahrami
- Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mohammad Reza Arabestani
- Department of Medical Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mohammad Taheri
- Department of Medical Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Abbas Farmany
- Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Fatemeh Norozzadeh
- Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Seyed Mostafa Hosseini
- Department of Medical Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hesam Nozari
- Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Fatemeh Nouri
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.
| |
Collapse
|
|
5
|
Razavipour M, Gonzalez M, Singh N, Cimenci CE, Chu N, Alarcon EI, Villafuerte J, Jodoin B. Biofilm Inhibition and Antiviral Response of Cold Sprayed and Shot Peened Copper Surfaces: Effect of Surface Morphology and Microstructure. JOURNAL OF THERMAL SPRAY TECHNOLOGY 2022; 31:130-144. [PMID: 37520908 PMCID: PMC8735887 DOI: 10.1007/s11666-021-01315-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 12/14/2021] [Accepted: 12/19/2021] [Indexed: 08/01/2023]
Abstract
Antibacterial properties of copper against planktonic bacteria population are affected by surface microstructure and topography. However, copper interactions with bacteria in a biofilm state are less studied. This work aims at better understanding the difference in biofilm inhibition of bulk, cold-sprayed, and shot-peened copper surfaces and gaining further insights on the underlying mechanisms using optical and scanning electron microscopy to investigate the topography and microstructure of the surfaces. The biofilm inhibition ability is reported for all surfaces. Results show that the biofilm inhibition performance of cold sprayed copper, while initially better, decreases with time and results in an almost identical performance than as-received copper after 18h incubation time. The shot-peened samples with a rough and ultrafine microstructure demonstrated an enhanced biofilm control, especially at 18 hr. The biofilm control mechanisms were explained by the diffusion rates and concentration of copper ions and the interaction between these ions and the biofilm, while surface topography plays a role in the bacteria attachment at the early planktonic state. Furthermore, the data suggest that surface topography plays a key role in antiviral activity of the materials tested, with a smooth surface being the most efficient. Graphical Abstract
Collapse
Affiliation(s)
- Maryam Razavipour
- Cold Spray Research Laboratory, University of Ottawa, Ottawa, ON Canada
| | - Mayte Gonzalez
- Division of Cardiac Surgery, BEaTS Research, University of Ottawa Heart Institute, Ottawa, Ontario Canada
| | - Naveen Singh
- Cold Spray Research Laboratory, University of Ottawa, Ottawa, ON Canada
| | - Cagla Eren Cimenci
- Division of Cardiac Surgery, BEaTS Research, University of Ottawa Heart Institute, Ottawa, Ontario Canada
| | - Nicole Chu
- Division of Cardiac Surgery, BEaTS Research, University of Ottawa Heart Institute, Ottawa, Ontario Canada
| | - Emilio I. Alarcon
- Division of Cardiac Surgery, BEaTS Research, University of Ottawa Heart Institute, Ottawa, Ontario Canada
- Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario Canada
| | | | - Bertrand Jodoin
- Cold Spray Research Laboratory, University of Ottawa, Ottawa, ON Canada
| |
Collapse
|
|
6
|
Sobczyk MK, Gaunt TR. The Effect of Circulating Zinc, Selenium, Copper and Vitamin K 1 on COVID-19 Outcomes: A Mendelian Randomization Study. Nutrients 2022; 14:233. [PMID: 35057415 PMCID: PMC8780111 DOI: 10.3390/nu14020233] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/15/2021] [Accepted: 12/16/2021] [Indexed: 12/22/2022] Open
Abstract
Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and immunomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 levels have a causal effect on COVID-19 related outcomes, including risk of infection, hospitalization and critical illness. Methods: We employed a two-sample Mendelian Randomization (MR) analysis. Our genetic variants derived from European-ancestry GWAS reflected circulating levels of Zn, Cu, Se in red blood cells as well as Se and vitamin K1 in serum/plasma. For the COVID-19 outcome GWAS, we used infection, hospitalization or critical illness. Our inverse-variance weighted (IVW) MR analysis was complemented by sensitivity analyses including a more liberal selection of variants at a genome-wide sub-significant threshold, MR-Egger and weighted median/mode tests. Results: Circulating micronutrient levels show limited evidence of association with COVID-19 infection, with the odds ratio [OR] ranging from 0.97 (95% CI: 0.87-1.08, p-value = 0.55) for zinc to 1.07 (95% CI: 1.00-1.14, p-value = 0.06)-i.e., no beneficial effect for copper was observed per 1 SD increase in exposure. Similarly minimal evidence was obtained for the hospitalization and critical illness outcomes with OR from 0.98 (95% CI: 0.87-1.09, p-value = 0.66) for vitamin K1 to 1.07 (95% CI: 0.88-1.29, p-value = 0.49) for copper, and from 0.93 (95% CI: 0.72-1.19, p-value = 0.55) for vitamin K1 to 1.21 (95% CI: 0.79-1.86, p-value = 0.39) for zinc, respectively. Conclusions: This study does not provide evidence that supplementation with zinc, selenium, copper or vitamin K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.
Collapse
Affiliation(s)
- Maria K. Sobczyk
- MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK;
| | | |
Collapse
|
|
7
|
Xiao D, Li W, Zhang WH, Wen Z, Dai B, Mo W, Qiu S, Yang L. Dietary Zinc, Copper, and Selenium Intake and High-Risk Human Papillomavirus Infection among American Women: Data from NHANES 2011-2016. Nutr Cancer 2022; 74:1958-1967. [PMID: 34553663 DOI: 10.1080/01635581.2021.1979603] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 09/03/2021] [Accepted: 09/03/2021] [Indexed: 11/11/2022]
Abstract
Studies have shown that the micronutrients, zinc (Zn), copper (Cu), and selenium (Se) are associated with the HPV-associated cervical cancer, yet between dietary Zn/Cu/Se intake and high-risk HPV (hrHPV) infection remain unclear. We obtained publicly available data in the present cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) performed between 2011 and 2016. Dietary Zn, Cu, and Se intakes were assessed from two 24-h diet recalls. A total of 4628 female with the age of 18-59 years were included in this secondary analysis. Comparing the highest with the lowest quartiles of Zn intake, the adjusted odds ratio (aOR) for hrHPV infection was 0.72 (95% CI, 0.54-0.98). The aOR upon comparison of the quartile three with the lowest quartile of Cu intake was 0.67 (95% CI, 0.50-0.90). Whereas no significant association was found between intakes of Se and hrHPV infection in multivariate analysis. Moreover, compared with those below the Recommended Dietary Allowance (RDA), hrHPV infection risk was significantly decreased among women who met the RDA for Cu (aOR: 0.74; 95% CI = 0.60-0.92), but not for Zn and Se. In conclusion, high dietary Zn and moderate copper intakes were independently and negatively associated with hrHPV infection in addition to Se.
Collapse
Affiliation(s)
- Di Xiao
- Department of Women, Children and Family Planning Information, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Weidong Li
- Department of Women, Children and Family Planning Information, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Wei-Hong Zhang
- International Center for Reproductive Health, Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
- Epidemiology, Biostatistics and Clinical Research Center, School of Public Health, Université Libre de Bruxelles (ULB), Bruxelles, Belgium
| | - Zihao Wen
- Department of Women, Children and Family Planning Information, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Bofeng Dai
- Department of Women, Children and Family Planning Information, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Weijian Mo
- Department of Women, Children and Family Planning Information, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Shiqiu Qiu
- Department of Hematology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Li Yang
- Department of Women, Children and Family Planning Information, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| |
Collapse
|
|
8
|
Rodriguez K, Saunier F, Rigaill J, Audoux E, Botelho-Nevers E, Prier A, Dickerscheit Y, Pillet S, Pozzetto B, Bourlet T, Verhoeven PO. Evaluation of in vitro activity of copper gluconate against SARS-CoV-2 using confocal microscopy-based high content screening. J Trace Elem Med Biol 2021; 68:126818. [PMID: 34274845 PMCID: PMC8264279 DOI: 10.1016/j.jtemb.2021.126818] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 06/08/2021] [Accepted: 07/06/2021] [Indexed: 12/13/2022]
Abstract
CONTEXT Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that emerged late in 2019 is the etiologic agent of coronavirus disease 2019 (Covid-19). There is an urgent need to develop curative and preventive therapeutics to limit the current pandemic and to prevent the re-emergence of Covid-19. This study aimed to assess the in vitro activity of copper gluconate against SARS-CoV-2. METHODS Vero E6 cells were cultured with or without copper gluconate 18-24 hours before infection. Cells were infected with a recombinant GFP expressing SARS-CoV-2. Cells were infected with a recombinant GFP expressing SARS-CoV-2. Infected cells were incubated in fresh medium containing varying concentration of copper gluconate (supplemented with bovine serum albumin or not) for an additional 48 -h period. The infection level was measured by the confocal microscopy-based high content screening method. The cell viability in presence of copper gluconate was assessed by XTT and propidium iodide assays. RESULTS The viability of Vero E6 cells exposed to copper gluconate up to 200 μM was found to be similar to that of unexposed cells, but it dropped below 70 % with 400 μM of this agent after 72 h of continuous exposure. The infection rate was 23.8 %, 18.9 %, 20.6 %, 6.9 %, 5.3 % and 5.2 % in cells treated prior infection with 0, 2, 10, 25, 50 and 100 μM of copper gluconate respectively. As compared to untreated cells, the number of infected cells was reduced by 71 %, 77 %, and 78 % with 25, 50, and 100 μM of copper gluconate respectively (p < 0.05). In cells treated only post-infection, the rate of infection dropped by 73 % with 100 μM of copper gluconate (p < 0.05). However, the antiviral activity of copper gluconate was abolished by the addition of bovine serum albumin. CONCLUSION Copper gluconate was found to mitigate SARS-CoV-2 infection in Vero E6 cells but this effect was abolished by albumin, which suggests that copper will not retain its activity in serum. Furthers studies are needed to investigate whether copper gluconate could be of benefit in mucosal administration such as mouthwash, nasal spray or aerosols.
Collapse
Affiliation(s)
- Killian Rodriguez
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France
| | - Florian Saunier
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France; Infectious Diseases Department, University Hospital of St-Etienne, France
| | - Josselin Rigaill
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France; Department of Infectious Agents and Hygiene, University Hospital of St-Etienne, France
| | - Estelle Audoux
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France
| | - Elisabeth Botelho-Nevers
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France; Infectious Diseases Department, University Hospital of St-Etienne, France
| | - Amélie Prier
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France
| | - Yann Dickerscheit
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France
| | - Sylvie Pillet
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France; Department of Infectious Agents and Hygiene, University Hospital of St-Etienne, France
| | - Bruno Pozzetto
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France; Department of Infectious Agents and Hygiene, University Hospital of St-Etienne, France
| | - Thomas Bourlet
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France; Department of Infectious Agents and Hygiene, University Hospital of St-Etienne, France
| | - Paul O Verhoeven
- CIRI, Centre International de Recherche en Infectiologie, GIMAP team, University of Lyon, University of St-Etienne, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, St-Etienne, France; Department of Infectious Agents and Hygiene, University Hospital of St-Etienne, France.
| |
Collapse
|
|
9
|
Rani I, Goyal A, Bhatnagar M, Manhas S, Goel P, Pal A, Prasad R. Potential molecular mechanisms of zinc- and copper-mediated antiviral activity on COVID-19. Nutr Res 2021; 92:109-128. [PMID: 34284268 PMCID: PMC8200255 DOI: 10.1016/j.nutres.2021.05.008] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 05/05/2021] [Accepted: 05/28/2021] [Indexed: 12/11/2022]
Abstract
Novel coronavirus disease 2019 (COVID-19) has spread across the globe; and surprisingly, no potentially protective or therapeutic antiviral molecules are available to treat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, zinc (Zn) and copper (Cu) have been shown to exert protective effects due to their antioxidant, anti-inflammatory, and antiviral properties. Therefore, it is hypothesized that supplementation with Zn and Cu alone or as an adjuvant may be beneficial with promising efficacy and a favorable safety profile to mitigate symptoms, as well as halt progression of the severe form of SARS-CoV-2 infection. The objective of this review is to discuss the proposed underlying molecular mechanisms and their implications for combating SARS-CoV-2 infection in response to Zn and Cu administration. Several clinical trials have also included the use of Zn as an adjuvant therapy with dietary regimens/antiviral drugs against COVID-19 infection. Overall, this review summarizes that nutritional intervention with Zn and Cu may offer an alternative treatment strategy by eliciting their virucidal effects through several fundamental molecular cascades, such as, modulation of immune responses, redox signaling, autophagy, and obstruction of viral entry and genome replication during SARS-CoV-2 infection.
Collapse
Affiliation(s)
- Isha Rani
- Department of Biochemistry, M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India
| | - Anmol Goyal
- Department of Community Medicine, Gian Sagar Medical College and Hospital, Banur, Patiala, Punjab, India
| | - Mini Bhatnagar
- Department of General Medicine, M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India
| | - Sunita Manhas
- Department of Biochemistry, M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India
| | - Parul Goel
- Department of Biochemistry, M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India
| | - Amit Pal
- Department of Biochemistry, AIIMS Kalyani, West Bengal, India
| | - Rajendra Prasad
- Department of Biochemistry, M.M. Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India.
| |
Collapse
|
|
10
|
Monette A, Mouland AJ. Zinc and Copper Ions Differentially Regulate Prion-Like Phase Separation Dynamics of Pan-Virus Nucleocapsid Biomolecular Condensates. Viruses 2020; 12:E1179. [PMID: 33081049 PMCID: PMC7589941 DOI: 10.3390/v12101179] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/05/2020] [Accepted: 10/12/2020] [Indexed: 02/08/2023] Open
Abstract
Liquid-liquid phase separation (LLPS) is a rapidly growing research focus due to numerous demonstrations that many cellular proteins phase-separate to form biomolecular condensates (BMCs) that nucleate membraneless organelles (MLOs). A growing repertoire of mechanisms supporting BMC formation, composition, dynamics, and functions are becoming elucidated. BMCs are now appreciated as required for several steps of gene regulation, while their deregulation promotes pathological aggregates, such as stress granules (SGs) and insoluble irreversible plaques that are hallmarks of neurodegenerative diseases. Treatment of BMC-related diseases will greatly benefit from identification of therapeutics preventing pathological aggregates while sparing BMCs required for cellular functions. Numerous viruses that block SG assembly also utilize or engineer BMCs for their replication. While BMC formation first depends on prion-like disordered protein domains (PrLDs), metal ion-controlled RNA-binding domains (RBDs) also orchestrate their formation. Virus replication and viral genomic RNA (vRNA) packaging dynamics involving nucleocapsid (NC) proteins and their orthologs rely on Zinc (Zn) availability, while virus morphology and infectivity are negatively influenced by excess Copper (Cu). While virus infections modify physiological metal homeostasis towards an increased copper to zinc ratio (Cu/Zn), how and why they do this remains elusive. Following our recent finding that pan-retroviruses employ Zn for NC-mediated LLPS for virus assembly, we present a pan-virus bioinformatics and literature meta-analysis study identifying metal-based mechanisms linking virus-induced BMCs to neurodegenerative disease processes. We discover that conserved degree and placement of PrLDs juxtaposing metal-regulated RBDs are associated with disease-causing prion-like proteins and are common features of viral proteins responsible for virus capsid assembly and structure. Virus infections both modulate gene expression of metalloproteins and interfere with metal homeostasis, representing an additional virus strategy impeding physiological and cellular antiviral responses. Our analyses reveal that metal-coordinated virus NC protein PrLDs initiate LLPS that nucleate pan-virus assembly and contribute to their persistence as cell-free infectious aerosol droplets. Virus aerosol droplets and insoluble neurological disease aggregates should be eliminated by physiological or environmental metals that outcompete PrLD-bound metals. While environmental metals can control virus spreading via aerosol droplets, therapeutic interference with metals or metalloproteins represent additional attractive avenues against pan-virus infection and virus-exacerbated neurological diseases.
Collapse
Affiliation(s)
- Anne Monette
- Lady Davis Institute at the Jewish General Hospital, Montréal, QC H3T 1E2, Canada
| | - Andrew J. Mouland
- Lady Davis Institute at the Jewish General Hospital, Montréal, QC H3T 1E2, Canada
- Department of Medicine, McGill University, Montréal, QC H4A 3J1, Canada
| |
Collapse
|
|
11
|
Andreou A, Trantza S, Filippou D, Sipsas N, Tsiodras S. COVID-19: The Potential Role of Copper and N-acetylcysteine (NAC) in a Combination of Candidate Antiviral Treatments Against SARS-CoV-2. In Vivo 2020; 34:1567-1588. [PMID: 32503814 PMCID: PMC8378025 DOI: 10.21873/invivo.11946] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/15/2020] [Accepted: 05/20/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND On March 11, 2020, the World Health Organization (WHO) declared the outbreak of coronavirus disease (COVID-19) a pandemic. Since then, thousands of people have suffered and died, making the need for a treatment of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) more crucial than ever. MATERIALS AND METHODS The authors carried out a search in PubMed, ClinicalTrials.gov and New England Journal of Medicine (NEJM) for COVID-19 to provide information on the most promising treatments against SARS-CoV-2. RESULTS Possible COVID-19 agents with promising efficacy and favorable safety profile were identified. The results support the combination of copper, N-acetylcysteine (NAC), colchicine and nitric oxide (NO) with candidate antiviral agents, remdesivir or EIDD-2801, as a treatment for patients positive for SARS-CoV-2. CONCLUSION The authors propose to study the effects of the combination of copper, NAC, colchicine, NO and currently used experimental antiviral agents, remdesivir or EIDD-2801, as a potential treatment scheme for SARS-COV-2.
Collapse
Affiliation(s)
- Andri Andreou
- Pharmaceutical Services, Ministry of Health of the Republic of Cyprus, Nicosia, Cyprus
| | | | - Demetrios Filippou
- National Organization for Medicines, Athens, Greece
- Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Nikolaos Sipsas
- Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Sotirios Tsiodras
- Medical School, National and Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
12
|
Hannaford PC, Ti A, Chipato T, Curtis KM. Copper intrauterine device use and HIV acquisition in women: a systematic review. BMJ SEXUAL & REPRODUCTIVE HEALTH 2020; 46:17-25. [PMID: 31919240 PMCID: PMC6978563 DOI: 10.1136/bmjsrh-2019-200512] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 12/06/2019] [Accepted: 12/10/2019] [Indexed: 05/12/2023]
Abstract
OBJECTIVES To review systematically copper intrauterine device (Cu-IUD) use and HIV acquisition in women. METHODS We searched Pubmed, Embase and the Cochrane Library between database inception and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using an unspecified IUD or Cu-IUD compared with non-hormonal or no contraceptive users, or hormonal contraceptive users. We extracted information from included studies, assessed study quality, and summarised study findings. RESULTS From 2494 publications identified, seven met our inclusion criteria. One randomised controlled trial (RCT), judged "informative with few limitations", found no statistically significant differences in HIV risk between users of the Cu-IUD and either intramuscular depot medroxyprogesterone acetate (DMPA-IM) or levonorgestrel implant. One observational study, deemed "informative but with important limitations", found no statistically significant difference in HIV incidence among IUD users compared with women who had tubal ligation or who were not using any contraception. Another "informative but with important limitations" observational study found no difference in HIV incidence between Cu-IUD users and DMPA or norethisterone enanthate injectable, or implant users. An RCT considered "unlikely to inform the primary question" also found no difference in HIV risk between Cu-IUD and progestogen-only injectable users. Findings from the other three "unlikely to inform the primary question" cohort studies were consistent with the more robust studies suggesting no increased risk of HIV acquisition among Cu-IUD users. CONCLUSION The collective evidence, including that from a large high-quality RCT, does not indicate an increased risk of HIV acquisition among users of Cu-IUDs.
Collapse
Affiliation(s)
| | - Angeline Ti
- Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
- Department of Family and Preventive Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Tsungai Chipato
- University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
| | - Kathryn M Curtis
- Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| |
Collapse
|
|
13
|
Nguyen VT, Trinh KS. In situ DEPOSITION OF COPPER NANOPARTICLES ON POLYETHYLENE TEREPHTHALATE FILTERS AND ANTIBACTERIAL TESTING AGAINST Escherichia coli AND Salmonella enterica. BRAZILIAN JOURNAL OF CHEMICAL ENGINEERING 2019. [DOI: 10.1590/0104-6632.20190364s20190208] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Vinh Tien Nguyen
- Ho Chi Minh City University of Technology and Education, Vietnam
| | - Khanh Son Trinh
- Ho Chi Minh City University of Technology and Education, Vietnam
| |
Collapse
|
|
14
|
The Use of Copper as an Antimicrobial Agent in Health Care, Including Obstetrics and Gynecology. Clin Microbiol Rev 2019; 32:32/4/e00125-18. [PMID: 31413046 DOI: 10.1128/cmr.00125-18] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Health care-associated infections (HAIs) are a global problem associated with significant morbidity and mortality. Controlling the spread of antimicrobial-resistant bacteria is a major public health challenge, and antimicrobial resistance has become one of the most important global problems in current times. The antimicrobial effect of copper has been known for centuries, and ongoing research is being conducted on the use of copper-coated hard and soft surfaces for reduction of microbial contamination and, subsequently, reduction of HAIs. This review provides an overview of the historical and current evidence of the antimicrobial and wound-healing properties of copper and explores its possible utility in obstetrics and gynecology.
Collapse
|
|
15
|
Shah KK, Verma R, Oleske JM, Scolpino A, Bogden JD. Essential trace elements and progression and management of HIV infection. Nutr Res 2019; 71:21-29. [PMID: 31668643 DOI: 10.1016/j.nutres.2019.08.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 07/25/2019] [Accepted: 08/01/2019] [Indexed: 01/09/2023]
Abstract
This review was written to update the review that we published in Nutrition Research in 2007 by examining studies published in the last 11 years which describe the effects of trace mineral deficiencies and micronutrient supplementation on HIV infection and its progression. In addition, we included studies that explore the interactions between Highly Active Anti-Retroviral Therapy (HAART) and micronutrient nutrition, focusing on the essential trace minerals. This review summarizes the results described in relevant articles that were identified by literature searches conducted using the OVID Medline database. Four of the nine essential trace minerals, specifically chromium, iron, selenium, and zinc, can influence HIV progression and/or its treatment. Notably, copper-containing filters may prevent transmission of the HIV virus via breastfeeding. However, there is a lack of good evidence to date that fluoride, iodine, manganese, or molybdenum influence HIV infection. Recent studies reveal that HAART can alter serum trace mineral and vitamin concentrations, but the effects vary based on the medications used. Although they have contributed useful new data, the sample sizes for most of these studies were too small to draw definitive conclusions for introducing changes in the management of HIV infection. Larger studies are needed to better understand and define the roles of trace mineral and vitamin deficiencies and micronutrient supplementation in the management and treatment of HIV-infected patients.
Collapse
Affiliation(s)
- Keneil K Shah
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD
| | - Rebeka Verma
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD
| | - James M Oleske
- Department of Pediatrics, Rutgers New Jersey Medical School, Newark, NJ
| | - Anthony Scolpino
- Department of Pediatrics, Rutgers New Jersey Medical School, Newark, NJ
| | - John D Bogden
- Department of Microbiology, Biochemistry, & Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ.
| |
Collapse
|
|
16
|
Sucipto TH, Churrotin S, Setyawati H, Kotaki T, Martak F, Soegijanto S. ANTIVIRAL ACTIVITY OF COPPER(II)CHLORIDE DIHYDRATE AGAINST DENGUE VIRUS TYPE-2 IN VERO CELL. INDONESIAN JOURNAL OF TROPICAL AND INFECTIOUS DISEASE 2017. [DOI: 10.20473/ijtid.v6i4.3806] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Infection of dengue virus (DENV) was number of globally significant emerging pathogen. Antiviral dengue therapies ar importantly needed to control emerging dengue. Dengue virus (DENV) is mosquito-borne arboviruses responsible for causing acute systemic diseases and grievous health conditions in humans. To date, there is no clinically approved dengue vaccine or antiviral for humans, even though there have been great efforts towards this end. Copper and copper compounds have more effective in inactivation viruses, likes an influenza virus and human immunodeficiency virus (HIV). Purpose in this project was investigated of Copper(II)chloride Dihydrate antiviral compound were further tested for inhibitory effect on the replication of DENV-2 in cell culture. DENV replication was measures by Enzyme linked Immunosorbent Assay (ELISA) with selectivity index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for compound. The maximal inhibitory concentration (IC50) of Copper(II)chloride Dihydrate against dengue virus type-2 was 0.13 μg/ml. The cytotoxic concentration (CC50) of compound against Vero cell was 5.03 μg/ml. The SI values for Copper(II)chloride Dihydrate 38.69. Result of this study suggest that Copper(II)chloride Dihydrate demonstated significant anti-DENV-2 inhibitory activities and not toxic in the Vero cells. Copper mechanisms play an important role in the prevention of copper toxicity, exposure to excessive levels of copper can result in a number of adverse health effects, as a result increased reactive oxygen species and oxidative damage to lipid, DNA, and proteins have been observed in human cell culture models or clinical syndromes of severe copper deficiency and inhibition was attributed to released cupric ions which react with cysteine residues on the surface of the protease.
Collapse
|
|
17
|
Pavelková M, Kubová K, Vysloužil J, Kejdušová M, Vetchý D, Celer V, Molinková D, Lobová D, Pechová A, Vysloužil J, Kulich P. Biological Effects of Drug-Free Alginate Beads Cross-Linked by Copper Ions Prepared Using External Ionotropic Gelation. AAPS PharmSciTech 2017; 18:1343-1354. [PMID: 27502404 DOI: 10.1208/s12249-016-0601-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 07/22/2016] [Indexed: 11/30/2022] Open
Abstract
External ionotropic gelation offers a unique possibility to entrap multivalent ions in a polymer structure. The aim of this experimental study was to prepare new drug-free sodium alginate (ALG) particles cross-linked by Cu2+ ions and to investigate their technological parameters (particle size, sphericity, surface topology, swelling capacity, copper content, release of Cu2+ ions, mucoadhesivity) and biological activity (cytotoxicity and efficiency against the most common vaginal pathogens-Herpes simplex, Escherichia coli, Candida albicans) with respect to potential vaginal administration. Beads prepared from NaALG dispersions (3 or 4%) were cross-linked by Cu2+ ions (0.5 or 1.0 M CuCl2) using external ionotropic gelation. Prepared mucoadhesive beads with particle size over 1000 μm exhibited sufficient sphericity (all ˃0.89) and copper content (214.8-249.07 g/kg), which increased with concentration of polymer and hardening solution. Dissolution behaviour was characterized by extended burst effect, followed by 2 h of copper release. The efficiency of all samples against the most common vaginal pathogens was observed at cytotoxic Cu2+ concentrations. Anti-HSV activity was demonstrated at a Cu2+ concentration of 546 mg/L. Antibacterial activity of beads (expressed as minimum inhibition concentration, MIC) was influenced mainly by the rate of Cu2+ release which was controlled by the extent of swelling capacity. Lower MIC values were found for E. coli in comparison with C. albicans. Sample ALG-3_1.0 exhibited the fastest copper release and was proved to be the most effective against both bacteria. This could be a result of its lower polymer concentration in combination with smaller particle size and thus larger surface area.
Collapse
|
|
18
|
In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate. Virol J 2015; 12:132. [PMID: 26319137 PMCID: PMC4552998 DOI: 10.1186/s12985-015-0358-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 08/13/2015] [Indexed: 11/10/2022] Open
Abstract
Background Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally. Methods CuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90. Results CuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 μg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose–response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 μg/mL. Conclusion These results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract. Electronic supplementary material The online version of this article (doi:10.1186/s12985-015-0358-5) contains supplementary material, which is available to authorized users.
Collapse
|
|
19
|
Bassett DC, Madzovska I, Beckwith KS, Melø TB, Obradovic B, Sikorski P. Dissolution of copper mineral phases in biological fluids and the controlled release of copper ions from mineralized alginate hydrogels. ACTA ACUST UNITED AC 2014; 10:015006. [PMID: 25546880 DOI: 10.1088/1748-6041/10/1/015006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Here we investigate the dissolution behaviour of copper minerals contained within biocompatible alginate hydrogels. Copper has a number of biological effects and has most recently been evaluated as an alternative to expensive and controversial growth factors for applications in tissue engineering. Precise control and sustained release of copper ions are important due to a narrow therapeutic window of this potentially toxic ion, and alginate would appear to be a good material of choice for this purpose. We found that aqueously insoluble copper minerals could be precipitated during gelling within or mixed into alginate hydrogels in the form of microbeads prior to gelling to serve as depots of copper. These minerals were found to be soluble in a variety of biological fluids relevant to in vitro and in vivo investigations, and the alginate carrier served as a barrier to diffusion of these ions and therefore offered control over the rate and duration of release (Cu(2+) release rates observed between 10-750 µMol g(-1) h(-1) and duration for up to 32 d). Copper mineral and copper mineralized alginate microbeads were characterized using powder x-ray diffraction, FTIR, thermogravimetric analysis and scanning electron microscopy. Dissolution kinetics were studied based on measurements of copper ion concentrations using colourimetric methods. In addition we characterized the complexes formed between released copper ions and biological fluids by electron paramagnetic spectroscopy which offers an insight into the behaviour of these materials in the body.
Collapse
Affiliation(s)
- David C Bassett
- Department of Physics, Norwegian University of Science and Technology, Trondheim, 7491, Norway
| | | | | | | | | | | |
Collapse
|
|
20
|
Engel RM, Morris M, Henning T, Ritter JM, Jones TL, Dietz S, Ayers J, Vishwanathan SA, Jenkins L, Zaki S, Wildemeersch D, Garber D, Powell N, Hendry RM, McNicholl J, Kersh EN. Evaluation of pigtail macaques as a model for the effects of copper intrauterine devices on HIV infection. J Med Primatol 2013; 43:349-59. [PMID: 24372425 DOI: 10.1111/jmp.12096] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2013] [Indexed: 12/01/2022]
Abstract
BACKGROUND Long-acting, hormonal contraception may increase HIV risk. Copper intrauterine devices (IUDs) could serve as non-hormonal alternatives. We pilot a pigtail macaque model for evaluating HIV susceptibility factors during copper IUD use. METHODS Frameless and flexible GyneFix(®) copper IUDs were surgically implanted into three SHIVSF 162p3 -positive macaques via hysterotomy and monitored for up to 4 months. Four macaques served as non-IUD controls. RESULTS All animals retained the devices without complications. No consistent change in vaginal viral RNA or inflammatory cytokines was seen. Two animals had altered menstrual cycles and experienced marked thinning of vaginal epithelium after IUD insertion. Histological examination of uterine tissue at necropsy revealed endometrial ulceration and lymphocytic inflammation with glandular loss at sites of direct IUD contact. CONCLUSIONS Although the need for insertion surgery could limit its usefulness, this model will allow studies on copper IUDs and SHIV shedding, disease progression, and HIV susceptibility factors.
Collapse
Affiliation(s)
- Robyn M Engel
- Animal Resources Branch, Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta, GA, USA
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Borkow G, Monk A. Fighting nosocomial infections with biocidal non-intrusive hard and soft surfaces. World J Clin Infect Dis 2012; 2:77-90. [DOI: 10.5495/wjcid.v2.i4.77] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Approximately 7 million people worldwide acquire a healthcare associated infection each year. Despite aggressive monitoring, hand washing campaigns and other infection control measures, nosocomial infections (NI) rates, especially those caused by antibiotic resistant pathogens, are unacceptably high worldwide. Additional ways to fight these infections need to be developed. A potential overlooked and neglected source of nosocomial pathogens are those found in non-intrusive soft and hard surfaces located in clinical settings. Soft surfaces, such as patient pyjamas and beddings, can be an excellent substrate for bacterial and fungal growth under appropriate temperature and humidity conditions as those present between patients and the bed. Bed making in hospitals releases large quantities of microorganisms into the air, which contaminate the immediate and non-immediate surroundings. Microbes can survive on hard surfaces, such as metal trays, bed rails and door knobs, for very prolonged periods of time. Thus soft and hard surfaces that are in direct or indirect contact with the patients can serve as a source of nosocomial pathogens. Recently it has been demonstrated that copper surfaces and copper oxide containing textiles have potent intrinsic biocidal properties. This manuscript reviews the recent laboratory and clinical studies, which demonstrate that biocidal surfaces made of copper or containing copper can reduce the microbiological burden and the NI rates.
Collapse
|
|
22
|
Shionoiri N, Sato T, Fujimori Y, Nakayama T, Nemoto M, Matsunaga T, Tanaka T. Investigation of the antiviral properties of copper iodide nanoparticles against feline calicivirus. J Biosci Bioeng 2012; 113:580-6. [DOI: 10.1016/j.jbiosc.2011.12.006] [Citation(s) in RCA: 87] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2011] [Revised: 12/03/2011] [Accepted: 12/13/2011] [Indexed: 12/11/2022]
|
|
23
|
Imai K, Ogawa H, Bui VN, Inoue H, Fukuda J, Ohba M, Yamamoto Y, Nakamura K. Inactivation of high and low pathogenic avian influenza virus H5 subtypes by copper ions incorporated in zeolite-textile materials. Antiviral Res 2012; 93:225-233. [DOI: 10.1016/j.antiviral.2011.11.017] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2011] [Revised: 11/28/2011] [Accepted: 11/29/2011] [Indexed: 10/14/2022]
|
|
24
|
Novel antiviral characteristics of nanosized copper(I) iodide particles showing inactivation activity against 2009 pandemic H1N1 influenza virus. Appl Environ Microbiol 2011; 78:951-5. [PMID: 22156433 DOI: 10.1128/aem.06284-11] [Citation(s) in RCA: 123] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
We investigated the antiviral activity of nanosized copper(I) iodide (CuI) particles having an average size of 160 nm. CuI particles showed aqueous stability and generated hydroxyl radicals, which were probably derived from monovalent copper (Cu(+)). We confirmed that CuI particles showed antiviral activity against an influenza A virus of swine origin (pandemic [H1N1] 2009) by plaque titration assay. The virus titer decreased in a dose-dependent manner upon incubation with CuI particles, with the 50% effective concentration being approximately 17 μg/ml after exposure for 60 min. SDS-PAGE analysis confirmed the inactivation of the virus due to the degradation of viral proteins such as hemagglutinin and neuraminidase by CuI. Electron spin resonance (ESR) spectroscopy revealed that CuI generates hydroxyl radicals in aqueous solution, and radical production was found to be blocked by the radical scavenger N-acetylcysteine. Taken together, these findings indicate that CuI particles exert antiviral activity by generating hydroxyl radicals. Thus, CuI may be a useful material for protecting against viral attacks and may be suitable for applications such as filters, face masks, protective clothing, and kitchen cloths.
Collapse
|
|
25
|
Assessment of the anti-biofouling potentials of a copper iodide-doped nylon mesh. Appl Microbiol Biotechnol 2011; 95:1043-50. [DOI: 10.1007/s00253-011-3720-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2011] [Revised: 10/28/2011] [Accepted: 11/08/2011] [Indexed: 10/15/2022]
|
|
26
|
Borkow G, Covington CY, Gautam B, Anzala O, Oyugi J, Juma M, Abdullah MS. Prevention of human immunodeficiency virus breastmilk transmission with copper oxide: proof-of-concept study. Breastfeed Med 2011; 6:165-70. [PMID: 21770731 DOI: 10.1089/bfm.2010.0090] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Human immunodeficiency virus type 1 (HIV-1) transmission through breastmilk is the chief modality through which HIV-1 is transmitted from HIV-1-infected mothers to their babies in developing countries, where alternative feeding options lack practical feasibility. The development of an approach to inactivate the HIV-1 virions ingested by an infant on a daily basis through breastmilk is thus of critical importance. METHODS Copper has potent virucidal properties. Stoichiometric concentrations of copper ions inactivate the HIV-1 protease, which is essential for viral replication. Cell-free and cell-associated HIV-1 infectivity is inhibited when the virus is exposed to copper oxide in a dose-dependent manner. Passage of high titers of a wide range of HIV-1 isolates, spiked in culture medium, through filters containing copper oxide powder resulted in their deactivation. RESULTS In the current study, we demonstrate that the infectivity of three different HIV-1 isolates, spiked in breastmilk obtained from HIV-1-seronegative donors, or of wild-type isolates found in breastmilk obtained from HIV-1-seropositive donors, is drastically reduced (>98%) when exposed to copper oxide. CONCLUSIONS This study is proof of concept that copper oxide is efficacious against HIV-1 found in breastmilk and serves as the basis for further research aimed at determining the possible effects that copper may have on the nutritional and anti-infective properties of breastmilk. Furthermore, this supports the continuing study of the feasibility of developing a filtering device, such as an "at-the-breast" disposable shield that can be used discreetly and safely by HIV-1-infected mothers during breastfeeding.
Collapse
|
|
27
|
Borkow G, Zhou SS, Page T, Gabbay J. A novel anti-influenza copper oxide containing respiratory face mask. PLoS One 2010; 5:e11295. [PMID: 20592763 PMCID: PMC2892464 DOI: 10.1371/journal.pone.0011295] [Citation(s) in RCA: 226] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2010] [Accepted: 06/01/2010] [Indexed: 12/22/2022] Open
Abstract
Background Protective respiratory face masks protect the nose and mouth of the wearer from vapor drops carrying viruses or other infectious pathogens. However, incorrect use and disposal may actually increase the risk of pathogen transmission, rather than reduce it, especially when masks are used by non-professionals such as the lay public. Copper oxide displays potent antiviral properties. A platform technology has been developed that permanently introduces copper oxide into polymeric materials, conferring them with potent biocidal properties. Methodology/Principal Findings We demonstrate that impregnation of copper oxide into respiratory protective face masks endows them with potent biocidal properties in addition to their inherent filtration properties. Both control and copper oxide impregnated masks filtered above 99.85% of aerosolized viruses when challenged with 5.66±0.51 and 6.17±0.37 log10TCID50 of human influenza A virus (H1N1) and avian influenza virus (H9N2), respectively, under simulated breathing conditions (28.3 L/min). Importantly, no infectious human influenza A viral titers were recovered from the copper oxide containing masks within 30 minutes (≤0.88 log10TCID50), while 4.67±1.35 log10TCID50 were recovered from the control masks. Similarly, the infectious avian influenza titers recovered from the copper oxide containing masks were ≤0.97±0.01 log10TCID50 and from the control masks 5.03±0.54 log10TCID50. The copper oxide containing masks successfully passed Bacterial Filtration Efficacy, Differential Pressure, Latex Particle Challenge, and Resistance to Penetration by Synthetic Blood tests designed to test the filtration properties of face masks in accordance with the European EN 14683:2005 and NIOSH N95 standards. Conclusions/Significance Impregnation of copper oxide into respiratory protective face masks endows them with potent anti-influenza biocidal properties without altering their physical barrier properties. The use of biocidal masks may significantly reduce the risk of hand or environmental contamination, and thereby subsequent infection, due to improper handling and disposal of the masks.
Collapse
|
|
28
|
Hennebel T, De Gusseme B, Boon N, Verstraete W. Biogenic metals in advanced water treatment. Trends Biotechnol 2009; 27:90-8. [DOI: 10.1016/j.tibtech.2008.11.002] [Citation(s) in RCA: 140] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2008] [Revised: 10/31/2008] [Accepted: 11/03/2008] [Indexed: 10/21/2022]
|
|
29
|
Horie M, Ogawa H, Yoshida Y, Yamada K, Hara A, Ozawa K, Matsuda S, Mizota C, Tani M, Yamamoto Y, Yamada M, Nakamura K, Imai K. Inactivation and morphological changes of avian influenza virus by copper ions. Arch Virol 2008; 153:1467-72. [PMID: 18592130 DOI: 10.1007/s00705-008-0154-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2008] [Accepted: 05/30/2008] [Indexed: 11/25/2022]
Abstract
The infectivity of the H9N2 virus to MDCK cells was time-dependently inhibited by Cu(2+) at concentrations of 2.5-250 microM. In 25 microM Cu(2+) solution, the virus titer decreased by approximately 3 and 4 log within 3 and 6 h, respectively. Compared to Cu(2+), Zn(2+) was much less effective in virus inactivation. The H9N2 virus hemagglutinin activity was not affected by 2.5-250 microM Cu(2+). The H9N2 virus neuraminidase (NA) activity was drastically reduced by 25 mM Cu(2+), marginally reduced by 250 microM Cu(2+), and not affected by 25 microM Cu(2+). Thus, we found that copper ions suppress the infectivity of influenza virus at lower concentrations at which neither NA nor hemagglutination inhibition occurs. Electron microscopic analysis revealed morphological abnormalities of the Cu(2+)-treated H9N2 virus. Additional studies should be undertaken to clarify the mechanism underlying the antiviral effect of copper ions on influenza virus.
Collapse
Affiliation(s)
- M Horie
- Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Photocatalytic antimicrobial activity of thin surface films of TiO2, CuO and TiO2/CuO dual layers on Escherichia coli and bacteriophage T4. Appl Microbiol Biotechnol 2008; 79:127-33. [DOI: 10.1007/s00253-008-1411-8] [Citation(s) in RCA: 100] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2007] [Revised: 02/11/2008] [Accepted: 02/12/2008] [Indexed: 11/26/2022]
|
|
31
|
Ghoneum M, Shaheen M. MRN-100, an Iron-based Compound, Possesses Anti-HIV Activity In Vitro. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2008; 7:427-32. [PMID: 18955328 PMCID: PMC2892344 DOI: 10.1093/ecam/nen019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2007] [Accepted: 02/14/2008] [Indexed: 11/14/2022]
Abstract
We examined the in vitro anti-human immunodeficiency virus (HIV) activity of MRN-100, an iron-based compound derived from bivalent and tervalent ferrates. MRN-100 action against HIV-1 (SF strain) was tested in primary cultures of peripheral blood mononuclear cells (MNC) by analyzing p24 antigen production and percent survival of MNC infected with HIV. MRN-100 at a concentration of 10% (v/v) inhibited HIV-1 replication in 11 out of 14 samples (79%). The percentage of suppression of p24 antigen was −12.3 to 100% at 10 days post-treatment. MRN-100 also exhibited a significant protective effect in the survival of HIV-1-infected MNC. MNC survival post-treatment was dose dependent, 70.4% ± 8.4, 83.6% ± 10.7 and 90% ± 11.4, at concentrations 2.5, 5 and 10% (v/v), respectively, as compared with 53% ± 4 for HIV-1-infected MNC without treatment. The effect was detected as early as 4 days and continued up to 11 days. Treatment with MRN-100 caused no significant change in proliferative response of MNC alone or cocultured with different mitogens: PHA and Con-A (activators of T cell function) and PWM (activator of CD4+ T cell-dependent B cells). We concluded that MRN-100 possesses anti-HIV activity in vitro and without an increase in lymphocyte proliferation, MRN-100 may be a useful agent for treating patients with acquired immunodeficiency syndrome.
Collapse
Affiliation(s)
- Mamdooh Ghoneum
- Department of Otolaryngology, Drew University of Medicine and Science, 1621 E. 120 Street, Los Angeles, CA 90059, USA
| | | |
Collapse
|
|
32
|
Deactivation of human immunodeficiency virus type 1 in medium by copper oxide-containing filters. Antimicrob Agents Chemother 2007; 52:518-25. [PMID: 18070974 DOI: 10.1128/aac.00899-07] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Human immunodeficiency virus type 1 (HIV-1) can be transmitted through breast-feeding and through contaminated blood donations. Copper has potent biocidal properties and has been found to inactivate HIV-1 infectivity. The objective of this study was to determine the capacity of copper-based filters to inactivate HIV-1 in culture media. Medium spiked with high titers of HIV-1 was exposed to copper oxide powder or copper oxide-impregnated fibers or passed through copper-based filters, and the infectious viral titers before and after treatment were determined. Cell-free and cell-associated HIV-1 infectivity was inhibited when exposed to copper oxide in a dose-dependent manner, without cytotoxicity at the active antiviral copper concentrations. Similar dose-dependent inhibition occurred when HIV-1 was exposed to copper-impregnated fibers. Filtration of HIV-1 through filters containing the copper powder or copper-impregnated fibers resulted in viral deactivation of all 12 wild-type or drug-resistant laboratory or clinical, macrophage-tropic and T-cell-tropic, clade A, B, or C, HIV-1 isolates tested. Viral inactivation was not strain specific. Thus, a novel means to inactivate HIV-1 in medium has been developed. This inexpensive methodology may significantly reduce HIV-1 transmission from "mother to child" and/or through blood donations if proven to be effective in breast milk or plasma and safe for use. The successful application of this technology may impact HIV-1 transmission, especially in developing countries where HIV-1 is rampant.
Collapse
|
|
33
|
Borkow G, Gabbay J. Putting copper into action: copper-impregnated products with potent biocidal activities. FASEB J 2004; 18:1728-30. [PMID: 15345689 DOI: 10.1096/fj.04-2029fje] [Citation(s) in RCA: 192] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Copper ions, either alone or in copper complexes, have been used for centuries to disinfect liquids, solids, and human tissue. Today copper is used as a water purifier, algaecide, fungicide, nematocide, molluscicide, and antibacterial and antifouling agent. Copper also displays potent antiviral activity. We hypothesized that introducing copper into clothing, bedding, and other articles would provide them with biocidal properties. A durable platform technology has been developed that introduces copper into cotton fibers, latex, and other polymeric materials. This study demonstrates the broad-spectrum antimicrobial (antibacterial, antiviral, antifungal) and antimite activities of copper-impregnated fibers and polyester products. This technology enabled the production of antiviral gloves and filters (which deactivate HIV-1 and other viruses), antibacterial self-sterilizing fabrics (which kill antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci), antifungal socks (which alleviate symptoms of athlete's foot), and anti-dust mite mattress covers (which reduce mite-related allergies). These products did not have skin-sensitizing properties, as determined by guine pig maximization and rabbit skin irritation tests. Our study demonstrates the potential use of copper in new applications. These applications address medical issues of the greatest importance, such as viral transmissions; nosocomial, or healthcare-associated, infections; and the spread of antibiotic-resistant bacteria.
Collapse
|
|
34
|
Abstract
Reactive oxygen species (ROS) are generated by many different cells. Singlet oxygen (1O(2)) and a reaction product of it, excited carbonyls (C=O*), are important ROS. 1O(2) and C=O* are nonradicalic and emit light (one photon/molecule) when returning to ground state oxygen. Especially activated polymorphonuclear neutrophil granulocytes (PMN) produce large amounts of 1O(2). Via activation of the respiratory burst (NADPH oxidase and myeloperoxidase) they synthesize hypochlorite (NaOCl) and chloramines (in particular N-chlorotaurine). Chloramines are selective and stable chemical generators of 1O(2). In the human organism, 1O(2) is both a signal and a weapon with therapeutic potency against very different pathogens, such as microbes, virus, cancer cells and thrombi. Chloramines at blood concentrations between 1 and 2 mmol/L inactivate lipid enveloped virus and chloramines at blood concentrations below 0.5 mmol/L, i.e. at oxidant concentrations that do not affect thrombocytes or hemostasis factors, act antithrombotically by activation of the physiologic PMN mediated fibrinolysis; this thrombolysis is of selective nature, i.e. it does not impair the hemostasis system of the patient allowing the antithrombotic treatment in patients where the current risky thrombolytic treatment is contraindicated. The action of 1O(2) might be compared to the signaling and destroying gunfire of soldiers directed against bandits at night, resulting in an autorecruitment of the physiological inflammatory response. Chloramines (such as the mild and untoxic oxidant chloramine T (N-chloro-p-toluene-sulfonamide)) and their signaling and destroying reaction product 1O(2) might be promising new therapeutic agents against a multitude of up to now refractory diseases.
Collapse
Affiliation(s)
- Thomas W Stief
- Department of Clinical Chemistry and Molecular Diagnostics, University Hospital, Marburg, Germany.
| |
Collapse
|
|
35
|
Sagripanti JL, Routson LB, Bonifacino AC, Lytle CD. Mechanism of copper-mediated inactivation of herpes simplex virus. Antimicrob Agents Chemother 1997; 41:812-7. [PMID: 9087495 PMCID: PMC163800 DOI: 10.1128/aac.41.4.812] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The inactivation of herpes simplex virus (HSV) by copper was enhanced by the following reducing agents at the indicated relative level: ascorbic acid >> hydrogen peroxide > cysteine. Treatment of HSV-infected cells with combinations of Cu(II) and ascorbate completely inhibited virus plaque formation to below 0.006% of the infectious virus input, while it maintained 30% viability for the host mammalian cells. The logarithm of the surviving fraction of HSV mediated by 1 mg of Cu(II) per liter and 100 mg of reducing agent per liter followed a linear relationship with the reaction time, in which the kinetic rate constant for each reducing agent was -0.87 min(-1) (r = 0.93) for ascorbate, -0.10 min(-1) (r = 0.97) for hydrogen peroxide, and -0.04 min(-1) (r = 0.97) for cysteine. The protective effects of metal chelators and catalase, the lack of effect of superoxide dismutase, and the partial protection conferred by free-radical scavengers suggest that the mechanism of copper-mediated HSV inactivation is similar to that previously reported for copper-mediated DNA damage. The sensitivity exhibited by HSV to Cu(II) and reducing agents, particularly ascorbate, might be useful in the development of therapeutic antiviral agents.
Collapse
Affiliation(s)
- J L Sagripanti
- Center for Devices and Radiological Health, Food and Drug Administration, Rockville, Maryland 20857, USA
| | | | | | | |
Collapse
|