ArticlePDF Available

Copper, An Ancient Remedy Returning to Fight Microbial, Fungal and Viral Infections

  • MedCu Technologies Ltd
  • Argaman Technologies Ltd.

Abstract and Figures

Copper has potent biocidal properties. Copper ions, either alone or in copper complexes, have been used for centuries to disinfect liquids, solids and human tissue. This manuscript reviews the biocidal mechanisms of copper and the current usages of copper and copper compounds as antibacterial, antifungal and antiviral agents, with emphasis on novel health related applications. These applications include the reduction of transmission of health-associated (nosocomial) pathogens, foodborne diseases, and dust mites loads and treatment of fungal foot infections and wounds. Possible future applications include filtration devices capable of deactivating viruses in solutions, such as contaminated blood products and breastmilk.
Content may be subject to copyright.
272 Current Chemical Biology, 2009, 3, 272-278
1872-3136/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd.
Copper, An Ancient Remedy Returning to Fight Microbial, Fungal and
Viral Infections
Gadi Borkow
and Jeffrey Gabbay
Cupron Scientific, Ligad Center 2, First Floor, Rechov HaMa'ayan 4, Modiin 71700, Israel
Abstract: Copper has potent biocidal properties. Copper ions, either alone or in copper complexes, have been used for
centuries to disinfect liquids, solids and human tissue. This manuscript reviews the biocidal mechanisms of copper and the
current usages of copper and copper compounds as antibacterial, antifungal and antiviral agents, with emphasis on novel
health related applications. These applications include the reduction of transmission of health-associated (nosocomial)
pathogens, foodborne diseases, and dust mites loads and treatment of fungal foot infections and wounds. Possible future
applications include filtration devices capable of deactivating viruses in solutions, such as contaminated blood products
and breastmilk.
Keywords: Copper, biocide, fungicide, antiviral, acaricidal, nosocomial infections, wound healing.
Copper has been used as a biocide for centuries [1]. In
ancient Egypt (2000 BC), copper was used to sterilize water
and wounds. The ancient Greeks in the time of Hippocrates
(400 BC) prescribed copper for pulmonary diseases and for
purifying drinking water. Gangajal, “Holy water”, given to
Hindu devotees to drink as a blessed offering, is stored in
copper utensils as it keeps the water sparkling clean. During
the Roman Empire, copper cooking utensils were used to
prevent the spread of disease. The early Phoenicians nailed
copper strips to ships’ hulls to inhibit fouling and thus in-
crease speed and maneuverability. The Aztecs used copper
oxide and malachite for treating skin conditions. Early
American pioneers moving west across the American conti-
nent put copper coins in large wooden water casks to provide
safe drinking water for their long journey. By the 18th cen-
tury, copper had come into wide clinical use in the Western
world in the treatment of lung and mental disorders. In the
Second World War, Japanese soldiers put pieces of copper in
their water bottles to help prevent dysentery. Copper sul-
phate was (and is still) highly prized by some inhabitants of
Africa and Asia for healing sores and skin diseases.
Were all these civilizations right in using copper for the
above mentioned purposes? Indeed they were! The following
sections review scientific studies demonstrating the potent
biocidal properties of copper and copper compounds and
their current uses in health related applications.
The wide use of copper due to its antifungal properties
started in 1761, when it was discovered that seed grains
soaked in copper sulphate inhibited seed-borne fungi. Within
a few decades, the practice of treating seed grains with cop-
per sulphate had become so general and effective that today
seed-borne fungi are no longer of any economic importance.
*Address correspondence to this author at the Cupron Scientific, Ligad
Center 2, First Floor, Rechov HaMa'ayan 4, Modiin 71700, Israel;
In the 1880s a mixture of copper sulphate, lime and water
(called “Bordeaux mixture") and a mixture of copper sul-
phate and sodium carbonate (called “Burgundy mixture”)
became the fungicide of choice in the U.S. and France, re-
spectively, for spraying grapes and vines to fight mildew.
The fungicidal properties of copper were demonstrated in
controlled laboratory studies starting in the early 1950s (e.g.
[2-4]) and since then copper and copper compounds have
been shown to effectively kill a wide range of yeast and
fungi such as Aspergillus carbonarius [5]; Aspergillus fumi-
gatus [6]; Aspergillus niger [6-8]; Aspergillus oryzae [7];
Candida albicans [6,8-13]; Cryptococcus neoformans [6];
Epidermophyton floccosum [6]; Microsporum canis [6]; My-
rothecium verrucaria [7]; Saccharomyces cerevisiae [14,15];
Torulopsis pintolopesii [9]; Trichoderma viride [7]; Tricho-
phyton mentagrophytes [7,8,13] and Tricophyton rubrum
[6,13]. Thus, copper fungicides have become indispensable
and many thousands of tons are used annually all over the
world in agriculture [16,17]. For example, copper sulphate
and copper hydroxide are employed for the control of downy
mildew on grapes and green slime in farm ponds, rice fields,
irrigation and drainage canals, rivers, lakes and swimming
pools [17]. However, copper compounds may be very toxic
to fish and other organisms. The environmental hazards re-
sulting from copper build-up in sediments and the need for
high dosages have led to a constant search for and produc-
tion of compounds that provide the copper in a chelated form
(e.g. [18-20]). Chelated copper is non-reactive with other
chemical constituents in the water. For example, the copper
water-insoluble compound, copper-8-quinolinolate and some
of its derivates [7] are used in fruit-handling equipment. This
compound is also used to reduce environmental contamina-
tion of fungi in hospitals at concentrations above 0.4 g/ml
[16], since infection with fungi, such as Aspergillus spp, is a
major problem among immunocompromised patients, such
as AIDS patients.
Copper sulphate has been in use since 1838 for preserv-
ing timber and is today the base for many proprietary wood
preservatives [21]. Copper is also used as the active ingredi-
ent in products that prevent roof moss formation, such as
Copper Fighting Microbial, Fungal and Viral Infections Current Chemical Biology, 2009, Vol. 3, No. 3 273
copper granules found in 3M Scotchgard™ Algae Resistant
Roofing System [22]. Interestingly, the growth of barnacles,
seaweed, tubeworms, and other organisms on boat bottoms
produces surface roughness that increases turbulent flow,
acoustic noise, drag, and fuel consumption. An average in-
crease of 10 m in hull roughness can result in a 1% increase
in fuel consumption! This has led to the painting of boat bot-
toms with copper-containing paints that reduce fouling and
microbial biofilm formation in ships and save energy [23],
and now copper is quite commonly used in antifouling paints
Several copper compounds, such as copper sulphate,
copper nitrate and cupric chloride-bis-n-dodecylamine, are
potent molluscicides. For example, the following snails have
been shown to be killed by these compounds: Biomphalaria
glabrata [26]; Biomphalaria alexandrina [27-29] and Lym-
naea natalenesis [28,29]. Control of snails may be an impor-
tant strategy in fighting some human diseases, such as bil-
harziasis. This disease is caused by a trematode parasite,
Schistosoma mansoni, which uses snails and humans as
The recognition that copper has potent antibacterial prop-
erties followed and was well established in laboratory studies
(for a recent review see reference [30]). Some examples in-
clude the killing by means of copper or copper compounds
of Acinetobacter calcoaceticus/baumannii [31,32]; Bacillus
subtilis [32,33]; Bacillus macerans [34]; Campylobacter
jejuni [35]; Citrobacter [32]; Clostridium difficile [36,37];
Enterococci [11,12]; Escherichia coli [10-12,32,33,38-41];
Legionella pneumophila [31,42,43]; Listeria monocytogenes
[12,44-46]; Klebsiella pneumoniae [32]; Mycobacterium
tuberculosis [47]; Pseudomonas aeruginosa [48]; Pseudo-
monas fluorescens [45]; Pseudomonas striata [34]; Salmo-
nella sp. [12,32,35,39]; Salmonella typhimurium [45,49];
Shewanella putrefaciens [45]; Shigella flexnerii [32];
Staphylococcus epidermidis [50]; Staphylococcus aureus
[10-12,31-33,41,45,46,51,52]; and Streptococcus [32,53].
Recent studies have demonstrated that non-soluble copper
compounds, such as glass coated with thin films of CuO
[54], degradable phosphate glass fibres impregnated with
CuO [50,53] or metallic and copper alloys
[35,36,38,40,44,47,51,55,56] have potent biocidal properties,
even against difficult bacterial spores [36]. Interestingly,
bacteria exposed to metallic copper surfaces do not enter a
viable but nonculturable physiological state, in which they
are viable but do not multiply, but are completely inactivated
[44]. Importantly, based on the vast amount of antimicrobial
efficacy testing (180 tests, utilizing 3235 control and test
samples, conducted in independent microbiology laborato-
ries) sponsored by the Copper Development Association
(CDA), the U.S. Environmental Protection Agency (EPA)
has recently (March 2008) approved the registration of cop-
per alloys as materials with antimicrobial properties, thus
allowing the CDA to make public health claims [57]. The
following statement is included in the registration: "When
cleaned regularly, antimicrobial copper alloys surfaces kill
greater than 99.9% of bacteria within two hours, and con-
tinue to kill more than 99% of bacteria even after repeated
contamination". These public health claims acknowledge
that copper, brass and bronze are capable of killing harmful,
potentially deadly bacteria, such as Methicillin-resistant S.
aureus (MRSA). MRSA is one of the most virulent strains of
antibiotic-resistant bacteria and a common cause of hospital-
and community-acquired infections. Copper is the first solid
surface material to receive this type of EPA registration.
Copper demonstrates potent antiviral (virucidal) activity
as well. The inactivation of the following enveloped or
nonenveloped, single- or double-stranded DNA or RNA vi-
ruses by copper and copper compounds, has been reported:
bacteriophages [58-62], Infectious Bronchitis Virus [63],
Poliovirus [61,64], Junin Virus [59], Herpes Simplex Virus
[58,59], Human Immunodeficiency Virus Type 1 (HIV-1)
[11,65-67], West Nile Virus [11], Coxsackie Virus Types B2
& B4, Echovirus 4 and Simian Rotavirus SA11 [68]. More
recently, the inactivation of Influenza A [55,65], Rhinovirus
2, Yellow Fever, Measles, Respiratory Syncytial Virus,
Parainfluenza 3, Punta Toro, Pichinde, Adenovirus Type 1,
Cytomegalovirus and Vaccinia [65] has been demonstrated.
Copper exerts its toxicity to microorganisms through
several parallel mechanisms, which eventually may lead to
the microorganisms’ death even within minutes of their ex-
posure to copper (e.g. [14,38,65]). It is likely that the first
site that copper damages is the microorganisms’ envelope.
Recently, Nan Li and his colleagues [69], by using atomic
force microscopy, force-distance curves and inductively
coupled plasma mass spectrometer tests, studied the effects
of austenitic (a solid solution of ferric carbide or carbon in
iron) stainless steel containing or not containing copper on
the plasma membrane of E. coli. They found that the copper
containing steel adhered to the bacteria plasma membrane,
via the electrostatic forces exerted by Cu
, to a significantly
greater extent than the austenitic stainless steel not contain-
ing copper. They reported that initial damage occurred to the
lipopolysaccharide patches on the outer plasma membrane,
which collapsed while the inner part of the bacteria remained
intact. Already in 1988, Ohsumi and colleagues reported that
elicits significant permeability changes in intact Sac-
charomyces cerevisiae cells [14], which depending on the
plasma membrane fatty acid composition and the membrane
permeability, increased markedly in cells enriched with
polyunsaturated fatty acids [70]. Extensive copper-induced
disruption of membrane integrity inevitably leads to loss of
cell viability. However, even relatively small alterations in
the physical properties of biological membranes can elicit
marked changes in the activities of many essential mem-
brane-dependent functions, including transport protein activ-
ity and ion permeability [71].
While copper may interact with many microbial proteins
without damaging them, such as with copper chaperones
(e.g. [72,73]), copper may damage many proteins, both on
the microorganism envelope or within the cell, especially
when found in high concentrations, above the threshold by
which many microorganisms can cope with excess copper.
This may occur via displacement of essential metals from
their native binding sites in the proteins, or via direct interac-
tions with the proteins. In both cases, conformational
changes in the protein structure or in the protein active site
may occur, resulting in the inhibition or neutralization of the
protein biological activities. For example, specific oxidation
of the cysteine in the active site of vaccinia H1-related pro-
tein tyrosine phosphatase by Cu
results in complete inacti-
274 Current Chemical Biology, 2009, Vol. 3, No. 3 Borkow and Gabbay
vation of the protein activity [74]. Another example is the
neutralization of HIV-1 protease, an essential protein for the
replication of the virus, by stoichiometric concentrations of
copper ions [75]. Direct inhibition by Cu
required the pres-
ence of cysteine residue(s) in the protease [75,76]. Copper
also may mediate free radical attack of amino acids, espe-
cially of histidine and proline, causing substantial protein
alterations and even protein cleavage [77,78].
Copper ions can also damage nucleic acids. By cross
linking within and between strands of DNA [79] copper may
cause helical structure disorders and DNA denaturation [80].
In single-stranded DNA, such as that found in many DNA
viruses, a copper binding site was found on average in every
three nucleotides [81]. Guanine-specific covalent binding of
in double stranded DNA was demonstrated following
crystallization (1.2-A resolution) of DNA soaked with cupric
chloride [82], explaining the observed specificity of Cu
induced oxidative DNA damage that occurs near guanine
residues [83]. It has been suggested that subsequent to the
specific binding of copper to deoxyribonucleic acids, re-
peated cyclic redox reactions generate several OH radicals
near the binding site causing multiple damage to the nucleic
acids [84]. When examining the effects of Cu
on purified
S. typhimurium DNA, DNA breakage occurred only when
the copper ions and H
were present, while no damage to
the DNA was detectable after incubation with the metal ions
alone or with H
alone [49], supporting the notion that
copper catalyzes the conversion of H
to hydroxyl radicals
[85], at least in vitro. Although copper binds DNA in vitro,
stronger competing ligands, such as glutathione and cysteine
[86,87], may remove copper away from the DNA in vivo.
Furthermore, recent studies using E. coli lacking copper ex-
port genes indicate that copper does not catalyze significant
oxidative DNA damage in vivo [86]. Electron paramagnetic
resonance spin trapping assays showed that the majority of
-oxidizable copper was located in the periplasm, away
from the DNA. However, it still may be that in some micro-
organisms, especially in viruses, copper oxidative damage to
the genetic material may occur through Fenton mechanisms.
Indirect toxic mechanisms have been suggested. For exam-
ple, exposure to high concentrations of copper may increase
the rate of H
generation [88], which could have acceler-
ated iron-mediated oxidative DNA damage [86].
In general, the redox cycling between Cu
and Cu
which can catalyze the production of highly hydroxyl radi-
cals, with subsequent damage to lipids, proteins, DNA and
other biomolecules [30,89], makes copper reactive and a
particularly effective antimicrobial. Other closely related
metals, such as zinc and nickel, do not readily undergo re-
dox-cycling reactions and are more stable in their various
cationic states. Zinc, which is an essential trace metal like
copper and well metabolized by humans, displays antifungal
properties [90]. Zinc pyrithione, for example, is widely used
as an antifouling agent in paints [91]. However, free zinc ion
in solution is highly toxic to plants, invertebrates, and even
to vertebrate fish [92] and in high dosage can promote oxida-
tive toxicity in humans [93]. Nickel, which also has potent
antimicrobial properties, is a known haematotoxic, immuno-
toxic, neurotoxic, genotoxic, nephrotoxic, hepatotoxic and
carcinogenic agent [94] and is therefore not used.
Many bacteria and fungi have different mechanisms to
deal with excess copper (reviewed in [30]). These include
exclusion by a permeability barrier, intra- and extra-cellular
sequestration by cell envelopes, active transport membrane
efflux pumps, reduction in the sensitivity of cellular targets
to copper ions, extracellular chelation or precipitation by
secreted metabolites including copper, and adaptation and
tolerance via upregulation of necessary genes in the presence
of copper (e.g. [95,96]). However, above a certain threshold
and time of exposure, which differs between the microorgan-
isms, they cannot deal with the copper overload and die. Due
to the multisite kill mechanism of copper and mostly non-
specific mechanisms of damage exerted by copper (see
above and [30]), their tolerance to copper is relatively low,
as compared to the resistance to antibiotics demonstrated by
some microorganisms (i.e., 10 fold lower sensitivity to cop-
per as opposed to 1000 fold less sensitivity to methicillin, for
example by methicillin resistant S. aureus). Thus, in contrast
to the highly resistant microbes that have evolved to antibiot-
ics in less than 50 years of use, tolerant microbes to copper
are extremely rare even though copper has been a part of the
earth for millions of years. Viruses do not have tolerance and
repair mechanisms, such as DNA repair mechanisms, as bac-
teria and fungi and thus are highly susceptible to copper in-
duced damage.
In contrast to the high susceptibility of microorganisms
to copper [30], copper is considered safe to humans, as dem-
onstrated by the widespread and prolonged use by women of
copper intrauterine devices [97-100]. The risk of adverse
reactions due to dermal contact with copper is considered
extremely low [101,102]. Copper is an essential trace ele-
ment involved in numerous human physiological and meta-
bolic processes [103,104], including in wound repair [105],
and many over-the-counter treatments for wound healing
contain copper [106,107]. The National Academy of Sci-
ences Committee established the U.S. Recommended Daily
Allowance of 0.9 mg of copper for normal adults [108].
Copper and copper-based compounds, due to their potent
biocidal properties, are now routinely used in several health-
related areas. These include 1) control of Legionella
[42,43,109-111] and other bacteria [112] in hospital water
distribution systems. Hospital-acquired Legionnaires' disease
has been reported from many hospitals since the first out-
break in 1976. Although cooling towers were linked to the
cases of Legionnaires' disease in the years after its discovery,
potable water has been the environmental source for almost
all reported hospital outbreaks [110,113]. Copper-silver ioni-
sation systems have emerged as the most successful long-
term disinfection method for hospital water disinfection sys-
tems [42,43,109-111]; 2) prevention of algae and other para-
sites growth in potable water reservoirs (e.g. [114,115]). The
efficacy of silver/copper/chlorine combinations in drinking
water for inactivation of protozoa such as Hartmannella
vermiformis and Naegleria fowleria [responsible for primary
amoebic meningoencephalitis] amoebas and Tetrahymena
pyriformis, is being explored [116,117]; 3) reduction of car-
ies in dentistry. Dental cements containing copper have been
shown to have antimicrobial and anticariogenic properties
[118,119]; 4) reduction of foodborne diseases through the
production and use of self-sterilizing metallic copper sur-
Copper Fighting Microbial, Fungal and Viral Infections Current Chemical Biology, 2009, Vol. 3, No. 3 275
faces [35,40,44,56] or materials containing copper
[11,12,53,54,120], in which the food is kept, handled or
transported. The addition of copper to drinking glasses has
been shown to reduce biofilm formation of Streptococcus
sanguis, thus reducing the risk of oral infections [53]. The
USA Centers for Disease Control (CDC) reported in 1999
that 76 million Americans (~25% of the population) suffer
from food poisoning annually. Recently they reported that
while several foodborne illnesses - yersinia, shigella, listeria,
sampylobacter, and shiga toxin-producing E. coli 0157 -
have become somewhat less common than they were in
1999, the overall rate of reported foodborne illness hasn't
budged much since 2004; and 5) in birth control by using
copper intrauterine contraceptive devices [100,121].
Novel uses of copper or copper-based compounds in
health-related applications are being explored and/or imple-
mented. One area is the reduction of transmission of health-
associated (nosocomial) pathogens in hospitals, clinics and
elderly homes, by i) making hospital hard surfaces, like door
knobs, bed rails, and intravenous stands, with metallic cop-
per [36,47,51,55] ii) making hospital soft surfaces, like
sheets, patient robes, patient pajamas, and nurse clothing,
from copper-impregnated biocidal textiles [11,12,122], and
iii) disinfecting contaminating cloths with copper-based bio-
cides [31].
Dust mites are considered to be an important source of
allergen for perennial rhinitis and asthmatic attacks [123].
Recently it was demonstrated that copper-impregnated fab-
rics are acaricidal [8,11]. Thus, elimination of house dust
mites in mattresses, quilts, carpets and pillows may improve
the quality of life of those suffering from dust-mite related
The use of copper-impregnated socks for the prevention
and treatment of fungal foot infections (athlete’s foot) has
been reported [13,124]. Similarly, the use of copper oxide
containing wound dressings for the reduction of dressing and
wound contamination has shown excellent results in human
and animal studies, not only in reducing the contamination of
the wounds, but more importantly in enhancing and allowing
wound repair, especially of diabetic ulcers in which conven-
tional treatment modalities failed in closing the wounds (un-
published data).
A possible application of copper due to its potent viruci-
dal properties is its use in filtration devices that can deacti-
vate viruses in contaminated solutions, such as contaminated
blood products and breastmilk. Recently the deactivation of
HIV-1 and other viruses in suspension by copper-based fil-
ters has been reported [65,66].
The capacity to impregnate copper into different textile
products, as well as into latex and other polymeric materials
[10-12] allows for the production of personal protective
equipment (PPE) with antimicrobial and antiviral properties
to be used by first responders and laboratory personnel, who
may be exposed to pathogens. PPE such as gloves, masks
and disposable robes, may increase the safety not only of
those using these products but of the immediate environment
and assure safer disposal of the used items. Similarly, police
or health-workers uniforms that may be exposed to contami-
nated solutions, such as blood, would reduce the risk of
pathogens transmission.
In contrast to the above copper health related applica-
tions, copper is not appropriate for use for systemic infec-
tions, mainly since once copper is ingested it readily inter-
acts with transport proteins as well as small molecular
weight ligands [125,126], making it unavailable as an antim-
icrobial. Furthermore, in cases where no efficacious copper
metabolism occurs, the unligated free copper in the body
may be involved in disease pathogenesis, such as in Alz-
heimer's disease [127]. Another limitation of copper may be
the price of copper, which has recently escalated. However,
this is of special relevance mainly when whole surfaces or
products are made with copper or copper alloys. It is signifi-
cantly less prohibitive when copper compounds, such as
copper oxide, are impregnated in low percentages in medical
devices or other health related products. In any case, when
compared to the alternatives or the consequences of not us-
ing copper-containing products, e.g., increased nosocomial
infections and food poisoning and the related costs of treat-
ments, the issue of the copper cost is not significant.
In conclusion, the safety of copper to humans and its po-
tent biocidal properties allow the use of copper in many ap-
plications (Fig. (1)), including several that address medical
concerns of the greatest importance. While some of these
applications are already being amply used, novel possible
applications of copper may have a major effect on our lives.
G.B. is the Chief Medical Scientist of Cupron. J.G. is the
CEO of Cupron. Cupron is a company that uses copper oxide
in its medical and consumer applications.
CDA = Copper Development Association
EPA = U.S. Environmental Protection Agency
Fig. (1). Current and future potential applications of copper and
copper compounds in different areas, which are based on copper’s
biocidal properties.
276 Current Chemical Biology, 2009, Vol. 3, No. 3 Borkow and Gabbay
MRSA = Methicillin-resistant Staphylococcus aureus
HIV-1 = Human Immunodeficiency Virus Type 1
PPE = Personal protective equipment
[1] Dollwet HHA, Sorenson JRJ. Historic uses of copper compounds
in medicine. Trace Elements Med 2001; 2: 80-7.
[2] Foye Wo, Van De Workeen IB Jr, Matthes JD. Copper complexes
of aromatic dithiocarbamates and their antifungal activity. J Am
Pharm Assoc Am Pharm Assoc (Baltim) 1958; 47: 556-8.
[3] Scigliano JA, Grubb TC, Shay DE. Fungicidal testing of some
organocopper compounds. J Am Pharm Assoc Am Pharm Assoc
1950; 39: 673-6.
[4] Benns BG, Gingras BA, Bayley CH. Antifungal Activity of Some
Thiosemicarbazones and Their Copper Complexes. Appl Microbiol
1960; 8: 353-6.
[5] Belli N, Marin S, Sanchis V, Ramos AJ. Impact of fungicides on
Aspergillus carbonarius growth and ochratoxin A production on
synthetic grape-like medium and on grapes. Food Addit Contam
2006; 23: 1021-9.
[6] Kumbhar AS, Padhye SB, Saraf AP, Mahajan HB, Chopade BA,
West DX. Novel broad-spectrum metal-based antifungal agents.
Correlations amongst the structural and biological properties of
copper (II) 2- acetylpyridine N4-dialkylthiosemicarbazones. Biol
Met 1991; 4: 141-3.
[7] Gershon H, Clarke DD, Gershon M. Synergistic antifungal action
of 8-quinolinol and its bischelate with copper(II) and with mixed
ligand chelates composed of copper(II), 8- quinolinol, and aromatic
hydroxy acids. J Pharm Sci 1989; 78: 975-8.
[8] Mumcuoglu KY, Gabbay J, Borkow G. Copper oxide impregnated
fabrics for the control of house dust mites. Int J Pest Manag 2008;
54: 235-40.
[9] Lin MY, Huang KJ, Kleven SH. In vitro comparison of the activity
of various antifungal drugs against new yeast isolates causing
thrush in poultry. Avian Dis 1989; 33: 416-21.
[10] Borkow G, Gabbay J. Endowing textiles with permanent potent
biocidal properties by impregnating them with copper oxide.
JTATM 2006; 5: 1.
[11] Borkow G, Gabbay J. Putting copper into action: copper-
impregnated products with potent biocidal activities. FASEB J
2004; 18: 1728-30.
[12] Gabbay J, Mishal J, Magen E, Zatcoff RC, Shemer-Avni Y,
Borkow G. Copper oxide impregnated textiles with potent biocidal
activities. J Ind Textiles 2006; 35: 323-35.
[13] Zatcoff RC, Smith MS, Borkow G. Treatment of tinea pedis with
socks containing copper impregnated fibers. Foot 2008; 18: 136-41.
[14] Ohsumi Y, Kitamoto K, Anraku Y. Changes induced in the perme-
ability barrier of the yeast plasma membrane by cupric ion. J Bacte-
riol 1988; 170: 2676-82.
[15] Vagabov VM, Ivanov AY, Kulakovskaya TV, Kulakovskaya EV,
Petrov VV, Kulaev IS. Efflux of potassium ions from cells and
spheroplasts of Saccharomyces cerevisiae yeast treated with silver
and copper ions. Biochemistry (Mosc) 2008; 73: 1224-7.
[16] Weber DJ, Rutala WH. In: Block SS, Ed, Disinfection, Sterilization
and Preservation. New York, Lippincott Williams and Wilkins,
2001; 415-30.
[17] La Torre A, Talocci S, Spera G, Valori R. Control of downy mil-
dew on grapes in organic viticulture. Commun Agric Appl Biol Sci
2008; 73: 169-78.
[18] Gershon H. Antifungal activity of bischelates of 5-,7-, and 5,7-
halogenated 8- quinolinols with copper(II). Determination of ap-
proximate dimensions of the long and short axes of the pores in the
fungal spore wall. J Med Chem 1974; 17: 824-7.
Cheng TC, Guida VG, Butler MS, Howland KH. Use of copper
compounds in shellfish depuration and disease control in maricul-
ture. 2001; Incra Project NO. 262B: 31.
[20] Chandra S, Raizada S, Tyagi M, Gautam A. Synthesis, spectro-
scopic, and antimicrobial studies on bivalent nickel and copper
complexes of bis(thiosemicrbazone). Bioinorg Chem Appl 2007;
2007: 51483. doi:10.1155/2007/51483.
Schultz TP, Nicholas DD, Preston AF. A brief review of the past,
present and future of wood preservation. Pest Manag Sci 2007; 63:
[22] 3M Industrial Mineral Products Division. The Schotchgard Algae
Resistant Roofing System. 2004.
[23] Cooney JJ, Tang RJ. Quantifying effects of antifouling paints on
microbial biofilm formation. Methods Enzymol 1999; 310: 637-44.
[24] Cooney TE. Bactericidal activity of copper and noncopper paints.
Infect Control Hosp Epidemiol 1995; 16: 444-50.
[25] UK Marine Sack Project. Copper-based antifouling paints. 2008.
[26] Oliveira-Filho EC, Lopes RM, Paumgartten FJ. Comparative study
on the susceptibility of freshwater species to copper-based pesti-
cides. Chemosphere 2004; 56: 369-74.
[27] Zidan ZH, Ragab FM, Mohamed KH. Molluscicidal activities of
certain pesticide and their mixtures against Biomphalaria alexan-
J Egypt Soc Parasitol 2002; 32: 285-96.
[28] Ragab F, Shoukry NM. Influence of certain fertilizers on the activ-
ity of some molluscicides against Biomphalaria alexandrina and
Lymnaea natalensis snails. J Egypt Soc Parasitol 2006; 36: 959-77.
[29] Hassan AA, Shoukary NM, Ismail NM. Efficacy of temperature,
and two commonly used molluscicides and fertilizers on Fasciola
gigantica eggs. J Egypt Soc Parasitol 2008; 38: 621-34.
[30] Borkow G, Gabbay J. Copper as a biocidal tool. Curr Med Chem
2005; 12: 2163-75.
[31] Gant VA, Wren MW, Rollins MS, Jeanes A, Hickok SS, Hall TJ.
Three novel highly charged copper-based biocides: safety and effi-
cacy against healthcare-associated organisms. J Antimicrob Che-
mother 2007; 60: 294-9.
[32] Cortes P, Atria AM, Contreras M, Garland MT, Pena O, Corsini G.
Magnetic properties and antibacterial activity of tetranuclear cop-
per complexes bridged by oxo group. J Chil Chem Soc 2006; 51:
[33] Ruparelia JP, Chatterjee AK, Duttagupta SP, Mukherji S. Strain
specificity in antimicrobial activity of silver and copper nanoparti-
cles. Acta Biomater 2008; 4: 707-16.
[34] Chandra S, Raizada S, Tyagi M, Sharma PK. Spectroscopic and
biological approach of Ni(II) and Cu(II) complexes of 2-
pyridinecarboxaldehyde thiosemicarbazone. Spectrochim Acta A
Mol Biomol Spectrosc 2008; 69: 816-21.
[35] Faundez G, Troncoso M, Navarrete P, Figueroa G. Antimicrobial
activity of copper surfaces against suspensions of Salmonella en-
terica and Campylobacter jejuni. BMC Microbiol 2004; 4: 19-25.
[36] Weaver L, Michels HT, Keevil CW. Survival of Clostridium diffi-
cile on copper and steel: futuristic options for hospital hygiene. J
Hosp Infect 2008; 68: 145-51.
[37] Wheeldon LJ, Worthington T, Lambert PA, Hilton AC, Lowden
CJ, Elliott TS. Antimicrobial efficacy of copper surfaces against
spores and vegetative cells of Clostridium difficile: the germination
theory. J Antimicrob Chemother 2008; 62: 522-5.
[38] Espirito SC, Taudte N, Nies DH, Grass G. Contribution of copper
ion resistance to survival of Escherichia coli on metallic copper
surfaces. Appl Environ Microbiol 2008; 74: 977-86.
Ibrahim SA, Yang H, Seo CW. Antimicrobial activity of lactic acid
and copper on growth of Salmonella and Eschericia coli 0157:H7
in laboratory medium and carrot juice. Food Chemistry 2008; 109:
[40] Noyce JO, Michels H, Keevil CW. Use of copper cast alloys to
control Escherichia coli O157 cross-contamination during food
processing. Appl Environ Microbiol 2006; 72: 4239-44.
[41] Ren G, Hu D, Cheng EW, Vargas-Reus MA, Reip P, Allaker RP.
Characterisation of copper oxide nanoparticles for antimicrobial
applications. Int J Antimicrob Agents 2009; 33(6): 587-90.
[42] Stout JE, Yu VL. Experiences of the first 16 hospitals using cop-
per-silver ionization for Legionella control: implications for the
evaluation of other disinfection modalities. Infect Control Hosp
Epidemiol 2003; 24: 563-8.
[43] Casari E, Ferrario A, Montanelli A. Prolonged effect of two com-
bined methods for Legionella disinfection in a hospital water sys-
tem. Ann Ig 2007; 19: 525-32.
[44] Wilks SA, Michels HT, Keevil CW. Survival of Listeria monocy-
togenes Scott A on metal surfaces: implications for cross-
contamination. Int J Food Microbiol 2006; 111: 93-8.
Russell SM. The effect of an acidic, copper sulfate-based commer-
cial sanitizer on indicator, pathogenic, and spoilage bacteria associ-
ated with broiler chicken carcasses when applied at various inter-
Copper Fighting Microbial, Fungal and Viral Infections Current Chemical Biology, 2009, Vol. 3, No. 3 277
vention points during poultry processing. Poult Sci 2008; 87: 1435-
[46] Lopez-Carballo G, Hernandez-Munoz P, Gavara R, Ocio MJ. Pho-
toactivated chlorophyllin-based gelatin films and coatings to pre-
vent microbial contamination of food products. Int J Food Micro-
biol 2008; 126: 65-70.
[47] Mehtar S, Wiid I, Todorov SD. The antimicrobial activity of cop-
per and copper alloys against nosocomial pathogens and Mycobac-
terium tuberculosis isolated from healthcare facilities in the West-
ern Cape: an in vitro study. J Hosp Infect 2008; 68: 45-51.
[48] Harrison JJ, Turner RJ, Joo DA, et al. Copper and quaternary am-
monium cations exert synergistic bactericidal and antibiofilm activ-
ity against Pseudomonas aeruginosa. Antimicrob Agents Che-
mother 2008; 52: 2870-81.
[49] Keyhani E, Abdi-Oskouei F, Attar F, Keyhani J. DNA strand
breaks by metal-induced oxygen radicals in purified Salmonella ty-
phimurium DNA. Ann N Y Acad Sci 2006; 1091: 52-64.
[50] Neel EA, Ahmed I, Pratten J, Nazhat SN, Knowles JC. Characteri-
sation of antibacterial copper releasing degradable phosphate glass
fibres. Biomaterials 2005; 26: 2247-54.
[51] Noyce JO, Michels H, Keevil CW. Potential use of copper surfaces
to reduce survival of epidemic meticillin-resistant Staphylococcus
aureus in the healthcare environment. J Hosp Infect 2006; 63: 289-
[52] Carson KC, Bartlett JG, Tan TJ, Riley TV. In vitro susceptibility of
methicillin-resistant Staphylococcus aureus and methicillin-
susceptible Staphylococcus aureus to a new antimicrobial, copper
silicate. Antimicrob Agents Chemother 2007; 51: 4505-7.
[53] Mulligan AM, Wilson M, Knowles JC. The effect of increasing
copper content in phosphate-based glasses on biofilms of Strepto-
coccus sanguis. Biomaterials 2003; 24: 1797-807.
[54] Ditta IB, Steele A, Liptrot C, et al. Photocatalytic antimicrobial
activity of thin surface films of TiO(2), CuO and TiO (2)/CuO dual
layers on Escherichia coli and bacteriophage T4. Appl Microbiol
Biotechnol 2008; 79: 127-33.
[55] Noyce JO, Michels H, Keevil CW. Inactivation of influenza A
virus on copper versus stainless steel surfaces. Appl Environ Mi-
crobiol 2007; 73: 2748-50.
[56] Wilks SA, Michels H, Keevil CW. The survival of Escherichia coli
O157 on a range of metal surfaces. Int J Food Microbiol 2005; 105:
[57] Copper Development Association. U.S. EPA Approves Registra-
tion of Antimicrobial Copper Alloys. Copper Development Asso-
ciation 2008.
[58] Sagripanti JL. Metal-based formulations with high microbicidal
activity. Appl Environ Microbiol 1992; 58: 3157-62.
[59] Sagripanti JL, Routson LB, Lytle CD. Virus inactivation by copper
or iron ions alone and in the presence of peroxide. Appl Environ
Microbiol 1993; 59: 4374-6.
[60] Wong K, Morgan AR, Parachych W. Controlled cleavage of phage
R17 RNA within the virion by treatment with ascorbate and copper
(II). Can J Biochem 2001; 52: 950.
[61] Yahaya MT, Straub TM, Yahaya MT. Inactivation of poliovirus
and bacteriophage MS-2 in copper, galvanised and plastic domestic
water pipes. Int Copper Res Assoc 2001; Project 48.
[62] Yamamoto N, HIATT CW, Haller W. Mechanism of inactivation
of bacteriophages by metals. Biochim Biophys Acta 1964; 91: 257-
[63] Jordan FT, Nassar TJ. The influence of copper on the survival of
infectious bronchitis vaccine virus in water. Vet Rec 1971; 89: 609-
[64] Totsuka A, Otaki K. The effects of amino acids and metals on the
infectivity of poliovirus ribonucleic acid. Jpn J Microbiol 1974; 18:
[65] Borkow G, Sidwell RW, Smee DF, et al. Neutralizing viruses in
suspensions by copper oxide based filters. Antimicrob Agents Che-
mother 2007; 51: 2605-7.
[66] Borkow G, Lara HH, Covington CY, Nyamathi A, Gabbay J. Deac-
tivation of human immunodeficiency virus type 1 in medium by
copper oxide-containing filters. Antimicrob Agents Chemother
2008; 52: 518-25.
Sagripanti JL, Lightfoote MM. Cupric and ferric ions inactivate
HIV. AIDS Res Hum Retroviruses 1996; 12: 333-7.
[68] The International Copper Association. Effects of copper and other
domestic plumbing materials on the survival of waterborne viruses.
[69] Nan L, Liu Y, Lu M, Yang K. Study on antibacterial mechanism of
copper-bearing austenitic antibacterial stainless steel by atomic
force microscopy. J Mater Sci Mater Med 2008; 19: 3057-62.
[70] Avery SV, Howlett NG, Radice S. Copper toxicity towards Sac-
charomyces cerevisiae: dependence on plasma membrane fatty acid
composition. Appl Environ Microbiol 1996; 62: 3960-6.
[71] Hazel JR, Williams EE. The role of alterations in membrane lipid
composition in enabling physiological adaptation of organisms to
their physical environment. Prog Lipid Res 1990; 29: 167-227.
[72] Hussain F, Sedlak E, Wittung-Stafshede P. Role of copper in fold-
ing and stability of cupredoxin-like copper-carrier protein CopC.
Arch Biochem Biophys 2007; 467: 58-66.
[73] Hussain F, Wittung-Stafshede P. Impact of cofactor on stability of
bacterial (CopZ) and human (Atox1) copper chaperones. Biochim
Biophys Acta 2007; 1774: 1316-22.
[74] Kim JH, Cho H, Ryu SE, Choi MU. Effects of metal ions on the
activity of protein tyrosine phosphatase VHR: highly potent and
reversible oxidative inactivation by Cu2+ ion. Arch Biochem Bio-
phys 2000; 382: 72-80.
[75] Karlstrom AR, Levine RL. Copper inhibits the protease from hu-
man immunodeficiency virus 1 by both cysteine-dependent and
cysteine-independent mechanisms. Proc Natl Acad Sci USA 1991;
88: 5552-6.
[76] Karlstrom AR, Shames BD, Levine RL. Reactivity of cysteine
residues in the protease from human immunodeficiency virus: iden-
tification of a surface-exposed region which affects enzyme func-
tion. Arch Biochem Biophys 1993; 304: 163-9.
[77] Davies MJ, Gilbert BC, Haywood RM. Radical-induced damage to
proteins: e.s.r. spin-trapping studies. Free Radic Res Commun
1991; 15: 111-27.
[78] Dean RT, Wolff SP, McElligott MA. Histidine and proline are
important sites of free radical damage to proteins. Free Radic Res
Commun 1989; 7: 97-103.
[79] Rifkind JM, Shin YA, Hiem JM, Eichorn GL. Co-operative disor-
dering of single stranded polynucleotides through copper crosslink-
ing. Biopolymers 2001; 15: 1879.
[80] Martin RB, Mariam YH. Metal Ions in Solution. Marcel Dekker:
New York, 2001.
[81] Sagripanti JL, Goering PL, Lamanna A. Interaction of copper with
DNA and antagonism by other metals. Toxicol Appl Pharmacol
1991; 110: 477-85.
[82] Geierstanger BH, Kagawa TF, Chen SL, Quigley GJ, Ho PS. Base-
specific binding of copper(II) to Z-DNA. The 1.3-A single crystal
structure of d(m5CGUAm5CG) in the presence of CuCl2. J Biol
Chem 1991; 266: 20185-91.
[83] Sagripant JL, Kraemer KH. Site-specific oxidative DNA damage at
polyguanosines produced by copper plus hydrogen peroxide. J Biol
Chem 1989; 264: 1729-34.
[84] Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal
ions. Free Radic Biol Med 1995; 18: 321-36.
[85] Gunther MR, Hanna PM, Mason RP, Cohen MS. Hydroxyl radical
formation from cuprous ion and hydrogen peroxide: a spin-trapping
study. Arch Biochem Biophys 1995; 316: 515-22.
[86] Macomber L, Rensing C, Imlay JA. Intracellular copper does not
catalyze the formation of oxidative DNA damage in Escherichia
coli. J Bacteriol 2007; 189: 1616-26.
[87] Schrammel A, Koesling D, Gorren AC, Chevion M, Schmidt K,
Mayer B. Inhibition of purified soluble guanylyl cyclase by copper
ions. Biochem Pharmacol 1996; 52: 1041-5.
[88] Manzl C, Enrich J, Ebner H, Dallinger R, Krumschnabel G. Cop-
per-induced formation of reactive oxygen species causes cell death
and disruption of calcium homeostasis in trout hepatocytes. Toxi-
cology 2004; 196: 57-64.
[89] Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative
stress. Curr Med Chem 2005; 12: 1161-208.
[90] Rieth H. [Killing of pathogenic fungi with organic zinc com-
pounds. Fungicidal aerosol disinfection and accumulative impreg-
nation]. Mykosen 1968; 11: 667-70.
Konstantinou IK, Albanis TA. Worldwide occurrence and effects
of antifouling paint booster biocides in the aquatic environment: a
review. Environ Int 2004; 30: 235-48.
Eisler R. Zinc Hazard to Fish, Wildlife, and Invertebrates: A Syn-
optic Review" Contaminant Hazard Reviews (Laurel, Maryland:
278 Current Chemical Biology, 2009, Vol. 3, No. 3 Borkow and Gabbay
U.S. Department of the Interior, Fish and Wildlife Service). 1993.
[93] Wright RO, Baccarelli A. Metals and neurotoxicology. J Nutr
2007; 137: 2809-13.
[94] Das KK, Das SN, Dhundasi SA. Nickel, its adverse health effects
& oxidative stress. Indian J Med Res 2008; 128: 412-25.
[95] Bersch B, Favier A, Schanda P, et al. Molecular structure and
metal-binding properties of the periplasmic CopK protein ex-
pressed in Cupriavidus metallidurans CH34 during copper chal-
lenge. J Mol Biol 2008; 380: 386-403.
[96] Magnani D, Barre O, Gerber SD, Solioz M. Characterization of the
CopR regulon of Lactococcus lactis IL1403. J Bacteriol 2008; 190:
[97] Anonymous. Copper IUDs, infection and infertility. Drug Ther
Bull 2002; 40: 67-9.
[98] Bastianelli C, Farris M, Benagiano G. Emergency contraception: a
review. Eur J Contracept Reprod Health Care 2008; 13: 9-16.
[99] Bilian X. Intrauterine devices. Best Pract Res Clin Obstet Gynaecol
2002; 16: 155-68.
[100] O'Brien PA, Kulier R, Helmerhorst FM, Usher-Patel M, d'Ar-
cangues C. Copper-containing, framed intrauterine devices for con-
traception: a systematic review of randomized controlled trials.
Contraception 2008; 77: 318-27.
[101] Hostynek JJ, Maibach HI. Copper hypersensitivity: dermatologic
aspects--an overview. Rev Environ Health 2003; 18: 153-83.
[102] Gorter RW, Butorac M, Cobian EP. Examination of the cutaneous
absorption of copper after the use of copper-containing ointments.
Am J Ther 2004; 11: 453-8.
[103] Olivares M, Uauy R. Copper as an essential nutrient. Am J Clin
Nutr 1996; 63: 791S-6S.
[104] Uauy R, Olivares M, Gonzalez M. Essentiality of copper in hu-
mans. Am J Clin Nutr 1998; 67: 952S-9S.
[105] Borkow G, Gabbay J, Zatcoff RC. Could chronic wounds not heal
due to too low local copper levels? Med Hypotheses 2008; 70: 610-
[106] Pereira CE, Felcman J. Correlation between five minerals and the
healing effect of Brazilian medicinal plants. Biol Trace Elem Res
1998; 65: 251-9.
[107] Schlemm DJ, Crowe MJ, McNeill RB, Stanley AE, Keller SJ.
Medicinal yeast extracts. Cell Stress Chaperones 1999; 4: 171-6.
[108] Trumbo P, Yates AA, Schlicker S, Poos M. Dietary reference in-
takes: vitamin A, vitamin K, arsenic, boron, chromium, copper, io-
dine, iron, manganese, molybdenum, nickel, silicon, vanadium, and
zinc. J Am Diet Assoc 2001; 101: 294-301.
[109] Chen YS, Lin YE, Liu YC, et al. Efficacy of point-of-entry copper-
-silver ionisation system in eradicating Legionella pneumophila in
a tropical tertiary care hospital: implications for hospitals contami-
nated with Legionella in both hot and cold water. J Hosp Infect
2008; 68: 152-8.
[110] Sabria M, Yu VL. Hospital-acquired legionellosis: solutions for a
preventable infection. Lancet Infect Dis 2002; 2: 368-73.
[111] Cachafeiro SP, Naveira IM, Garcia IG. Is copper-silver ionisation
safe and effective in controlling legionella? J Hosp Infect 2007; 67:
[112] Huang HI, Shih HY, Lee CM, Yang TC, Lay JJ, Lin YE. In vitro
efficacy of copper and silver ions in eradicating Pseudomonas
aeruginosa, Stenotrophomonas maltophilia and Acinetobacter
baumannii: implications for on-site disinfection for hospital infec-
tion control. Water Res 2008; 42: 73-80.
[113] Lin Yu, Vidic R, Stout JE, Yu VL. Legionella in water distribution
systems. JAWWA 2001; 90: 112-21.
[114] Applied Biochemist Company. Products for Water Quality. 2008.
[115] SePro Company. Captain Liquid Copper Algaecide. 2008.
[116] Rohr U, Weber S, Selenka F, Wilhelm M. Impact of silver and
copper on the survival of amoebae and ciliated protozoa in vitro.
Int J Hyg Environ Health 2000; 203: 87-9.
[117] Hambidge A. Reviewing efficacy of alternative water treatment
techniques. Health Estate 2001; 55: 23-5.
[118] Mahler DB. The high-copper dental amalgam alloys. J Dent Res
1997; 76: 537-41.
[119] Thneibat A, Fontana M, Cochran MA, et al. Anticariogenic and
antibacterial properties of a copper varnish using an in vitro micro-
bial caries model. Oper Dent 2008; 33: 142-8.
[120] Soto M, Chavez G, Baez M, Martinez C, Chaidez C. Internalization
of Salmonella typhimurium into mango pulp and prevention of fruit
pulp contamination by chlorine and copper ions. Int J Environ
Health Res 2007; 17: 453-9.
[121] Fantasia HC. Options for intrauterine contraception. J Obstet Gy-
necol Neonatal Nurs 2008; 37: 375-83.
[122] Borkow G, Gabbay J. Biocidal textiles can help fight nosocomial
infections. Med Hypotheses 2008; 70: 990-4.
[123] Brunton SA, Saphir RL. Dust mites and asthma. Hosp Pract (Off
Ed) 1999; 34: 67-76.
[124] Zatcoff RC. HealthStide
Socks - Footware to a higher standard.
Podiatry Management 2005; November/December: 202-3.
[125] Harris ED, Qian Y, Reddy MC. Genes regulating copper metabo-
lism. Mol Cell Biochem 1998; 188: 57-62.
[126] Krupanidhi S, Sreekumar A, Sanjeevi CB. Copper & biological
health. Indian J Med Res 2008; 128: 448-61.
[127] Brewer GJ. The risks of free copper in the body and the develop-
ment of useful anticopper drugs. Curr Opin Clin Nutr Metab Care
2008; 11: 727-32.
Received: December 18, 2008 Revised: April 08, 2009 Accepted: April 24, 2009
... Incorporating inorganic metal nanomaterials into materials is a promising way to improve antibacterial activity. For example, Ag [11][12][13][14][15][16], Cu [4,17,18], ZnO [19,20], and MoS 2 [21] nanomaterials have been identified as the preferred antibacterial additives for use in fabrics or face masks. Among them, copper has been used for centuries because it is less expensive than other noble metals, and has good biocidal properties [22]. ...
... The choice of carrier for loading nano-copper ions is very critical. In response to the call for environmental protection and resource conservation, natural biopolymers have been extracted [25], including cellulose [21,[26][27][28], chitosan [10,[29][30][31], and alginate [8,32,33], etc. Cellulose, the most prevalent natural biopolymer on earth, has revealed promising potential because of its inexhaustibility, economy, chemical uniqueness, biocompatibility, and biodegradability. Shaban et al. [34] used cotton fabrics (CF) to prepare ZnO NPs-modified fiber with super contact angle and excellent antibacterial activities under non-photocatalytic reaction through the spin coating technique. ...
... After modification, the fibers demonstrated improved antibacterial activity against various bacteria, particularly K. pneumonia. Kumar et al. [21] developed the 2D molybdenum disulfide (MoS 2 ) nanosheets antibacterial polycotton fabrics using a one-step vacuum filtration process. MoS 2 -modified fabric was used to prepare the antibacterial surgical mask, which had found outstanding mechanical properties and antibacterial activity against both Gram-negative and Gram-positive bacteria. ...
The current SARS-CoV-2 pandemic has resulted in the widespread use of personal protective equipment, particularly face masks. However, the use of commercial disposable face masks puts great pressure on the environment. In this study, nano-copper ions assembled cotton fabric used in face masks to impart antibacterial activity has been discussed. To produce the nanocomposite, the cotton fabric was modified by sodium chloroacetate after its mercerization, and assembled with bactericidal nano-copper ions (about 10.61 mg·g−1) through electrostatic adsorption. It demonstrated excellent antibacterial activity against Staphylococcus aureus and Escherichia coli because the gaps between fibers in the cotton fabric allow the nano-copper ions to be fully released. Moreover, the antibacterial efficiency was maintained even after 50 washing cycles. Furthermore, the face mask constructed with this novel nanocomposite upper layer exhibited a high particle filtration efficiency (96.08% ± 0.91%) without compromising the air permeability (28.9 min·L−1). This green, economical, facile, and scalable process of depositing nano-copper ions onto modified cotton fibric has great potential to reduce disease transmission, resource consumption, and environmental impact of waste, while also expanding the range of protective fabrics.
... A wide variety of materials or chemicals have been exploited as the active ingredient in antimicrobial coatings. Examples are polymers that possess antimicrobial properties, such as polyamines, [9,10] polyimines [11,12], layer by layer fabrication of polycations and polyanions, [13,14] side chain modified polyacrylates [15], and inorganic materials containing metal ions, including copper [16,17], silver [18,19], zinc [20], gold [21], their oxides [22][23][24], or alloys. ...
... The native surface of metallic copper is oxidized, and it is likely that many copper metal surfaces that have been studied have a surface that is primarily oxidized copper. Metallic copper and its oxides have shown antimicrobial activity against a broad range of pathogens, including bacteria, mycobacteria, and fungi [16,17,22,23,[25][26][27][28][29][30][31][32]94,95]. We focus on microparticles (1 µm < diameter < 10 µm) in order to avoid the possible hazards of nanoparticles. ...
Some very effective antimicrobial coatings exploit copper or cuprous oxide (Cu2O) as the active agent. The aim of this study is to determine which species is the active antimicrobial - dissolved ions, the Cu2O solid, or reactive oxygen species. Copper ions were leached from Cu2O into various solutions and the leachate tested for both dissolved copper and the efficacy in killing Pseudomonas aeruginosa. The concentration of copper species leached from Cu2O into aqueous solution varied greatly with the composition of the aqueous solution. For a range of solution buffers, killing of P. aeruginosa was highly correlated with the concentration of copper in the leachate. Further, 10 µL bacterial suspension droplets were placed on Cu2O coatings, with or without a polymer barrier layer, and tested for bacterial kill. Killing occurred without contact between bacterium and solid, demonstrating that contact with Cu2O is not necessary. We therefore conclude that soluble copper species are the antimicrobial agent, and that the most potent species is Cu+. The solid quickly raises and sustains the concentration of soluble copper species near the bacterium. Killing via soluble copper ions rather than contact should allow copper coatings to kill bacteria even when fouled, which is an important practical consideration.
... Bactericidal potential of M. piperita extract, and CuNPs against Methicillin-resistant Staphylococcus aureus as investigated by disc diffusion assay. The antibacterial activity of NPs is best explained by their high surface area per volume and simple permeability [22]. The bactericidal properties of CuNPs are mainly attributed to copper cations released by CuNPs, attached to the bacterial cell wall with electrostatic attraction ultimately rupturing it, causing protein denaturation and dissipation of the proton motive force and cell lysis [57]. ...
... Morphological observation and histopathological examination of wound tissues further confirmed the superiority of the green synthesis approach. CuNPs intensified activity is endorsed to its strong antimicrobial potential that assists in the reduction of the microbial load at the wounded area and improves healing process [22,59]. M. piperita based CuNP stimulate healing mechanism efficiently as it is rich in bioactive components such as essential oils, flavonoids, phenols that promote anti-inflammatory responses [24]. ...
Full-text available
Present research reports the enhanced diabetic wound healing potential of copper nanoparticles (CuNPs) synthesized from Mentha piperita obtained from high-altitude areas. Medioresinol was identified as a novel metabolite in M. piperita methanolic extract through Liquid chromatographic-tandem mass spectrometric analysis (LC-MS/MS). UV-vis and Fourier transform infrared spectroscopy confirm NPs with the presence of phenolic, amino, and ether groups. Spherical-shaped NPs with an average size of 100 nm were revealed by scanning electron microscopy. The bactericidal efficacy of CuNPs (2 mg/ml) against methicillin-resistant Staphylococcus aureus with an 18.3 mm inhibition zone was observed. CuNPs vividly possess antiglycation potential with 80% inhibition compared to M. piperita extract at 69%. Excision wounds were created on diabetic rats after receiving a single injection of alloxan monohydrate (150 mg/kg). One hour post diabetic induction, rats were treated with a topical formulation of CuNP-gel at 5-30mg/kg for 20 days and wound morphological parameters along with histopathological changes were evaluated. Conclusively, M. piperita-based CuNPs proved a critical role in wound epithelialization, proliferation, and differentiation with improved wound contraction in a dose-dependent manner, with 25 mg/kg as the best dose compared to positive and negative control groups. M. piperita metabolites enhanced the CuNP bactericidal and antidiabetic potential, along with wound healing activity in-vivo and in-vitro.
... In this regard, the literature contains examples of utilizing a formation of coordination compounds with FQ, which has led to the development of improved antibacterial agents [19][20][21][22][23][24][25][26]. Among all metals, Cu 2+ and Ag + metals constitute excellent alternatives [27,28] owing to their excellent antibacterial activity [29][30][31][32][33]. ...
Full-text available
Antibiotic resistance is a global problem and bacterial biofilms contribute to its development. In this context, this study aimed to perform the synthesis and characterization of seven materials based on silica mesoporous nanoparticles functionalized with three types of fluoroquinolones, along with Cu2+ or Ag+ species to evaluate the antibacterial properties against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa, including clinical and multi-drug-resistant strains of S. aureus and P. aeruginosa. In addition, in order to obtain an effective material to promote wound healing, a well-known proliferative agent, phenytoin sodium, was adsorbed onto one of the silver-functionalized materials. Furthermore, biofilm studies and the generation of reactive oxygen species (ROS) were also carried out to determine the antibacterial potential of the synthesized materials. In this sense, the Cu2+ materials showed antibacterial activity against S. aureus and E. coli, potentially due to increased ROS generation (up to 3 times), whereas the Ag+ materials exhibited a broader spectrum of activity, even inhibiting clinical strains of MRSA and P. aeruginosa. In particular, the Ag+ material with phenytoin sodium showed the ability to reduce biofilm development by up to 55% and inhibit bacterial growth in a "wound-like medium" by up to 89.33%.
... If different studies already highlighted some interest in studying past remedies or highlighted antibiotic use from past records, i.e. [33][34][35][36][37][38][39][40] , the consideration of these past remedies as a reservoir of pertinent strategies to combat infection would require more complex and coordinated strategies, involving intense collaboration between art, social and experimental sciences. ...
Full-text available
The proliferation and prevalence of antibiotic-resistant bacteria despite modern medicine is considered as one of the most alarming threats to global health. The fear that antibiotics that work today might not work tomorrow makes it imperative to search and develop novel drugs or therapeutic strategies to fight against micro-organisms resistant to our current approaches. From many centuries, people have sought solutions to combat infections and proposed countless remedies, traces of which can be found in manuscripts preserved over the past centuries. The re-examination and exploitation of these ancient remedies might be a key to a vast pool of potential therapeutic strategies or drug candidates against antibiotic-resistant pathogens. This, however, would first require the consideration of these ancient solutions as scientifically pertinent leads for new therapies. The aim of this review is to highlight arguments in favor of a rationality in the scientific approach of these past physicians as well as of a medicinal interest in studying these ancient pharmacopeias. To narrow the scope of our research, we focused on the Arab Medieval Golden Medical Age, which inspired occidental medicine hundreds of years after its preeminence. We further highlight the possibility of integrating this knowledge into innovative, modern therapeutic approaches.
... In ancient times copper metal and its salts were used to treat people having different conditions or wounds [1,2]. Recently it was shown that copper complex compounds could fight against cancer [3], copper nanoparticles to fight against viruses and bugs [4][5][6], copper oxides nanoparticles to fight against nosocomial infections [7][8][9], and so many other applications of copper derivatives. Copper is considered essential and safe to humans [10][11][12][13]. ...
... They are also used as additives in plastics, metallic coatings, lubricants, and inks, as well as in various skin products (Singh et al., 2016;Longano et al., 2012). Moreover, CuO NPs have antiviral and antimicrobial properties (Borkow and Gabbay, 2004;Borkow and Gabbay, 2009). CuO NPs are thus employed to impart biocidal action to fabrics including socks, wound dressings, and face masks (Borkow et al., 2010). ...
Copper oxide nanoparticles (CuO NPs) have received increasing interest due to their distinctive properties, including small particle size, high surface area, and reactivity. Due to these properties, their applications have been expanded rapidly in various areas such as biomedical properties, industrial catalysts, gas sensors, electronic materials, and environmental remediation. However, because of these widespread uses, there is now an increased risk of human exposure, which could lead to short- and long-term toxicity. This review addresses the underlying toxicity mechanisms of CuO NPs in cells which include reactive oxygen species generation, leaching of Cu ion, coordination effects, non-homeostasis effect, autophagy, and inflammation. In addition, different key factors responsible for toxicity, characterization, surface modification, dissolution, NPs dose, exposure pathways and environment are discussed to understand the toxicological impact of CuO NPs. In vitro and in vivo studies have shown that CuO NPs cause oxidative stress, cytotoxicity, genotoxicity, immunotoxicity, neurotoxicity, and inflammation in bacterial, algal, fish, rodents, and human cell lines. Therefore, to make CuO NPs a more suitable candidate for various applications, it is essential to address their potential toxic effects, and hence, more studies should be done on the long-term and chronic impacts of CuO NPs at different concentrations to assure the safe usage of CuO NPs.
... Bordeaux solution was known globally, as an effective fungicide includes copper sulfate and lime water. This mixture was invented by French scientists and developed into plant protector against disease as downy mildew infection onto the grape trees [2]. Copper sulfate is a key ingredient in most of the commercially available fungicides for farm and garden. ...
Full-text available
For many decades, Cu2+ ions have been used as fungicides in agriculture. However, the accumulation of Cu2+ ions in the soil ecosystem will be disadvantage for environment. Thus, the substitution of copper nanoparticles for Cu2+ ion is necessary to develop long-term efficient, eco-friendly, and cost-effective fungicides. In this study, the copper nanoparticles were synthesized by chemical reduction method of Cu2+ with reductive agent of NaHB4 in chitosan stabilizer. Characterizations of copper nanoparticles were determined by UV-Vis spectra, Fourier transform infrared spectroscopy, X ray diffraction patterns and Transmission Electron Microscopy images. The antifungal efficacy of CuNPs was evaluated by testing against Fusarium oxysporum fungi at various concentrations from 20 -100 ppm. The results revealed that copper nanoparticles samples inhibited significantly the growth of Fusarium oxysporum and the smaller diameter is, the higher antifungal efficacy is. The copper nanoparticles with 26.5 nm expressed an antifungal efficacy is higher than copper nanoparticles with 29 nm. The complete inhibition was observed at concentrations  80 ppm after 1 day and even 7 days of incubation for 2.0 CuNPs (26.5 nm) sample while fungi still survive on PDA plates containing 1.5 CuNPs (29 nm).
... Given its nature, copper is also an interesting material for thermal spraying applications in electronics, aerospace, medical applications, etc. Nevertheless, due to copper's melting point of 1084 °C, High-Velocity Oxy-Fuel (HVOF) or other high-temperature thermal spray techniques can result in melting and undesired oxidation [1], [2]. ...
Conference Paper
As a supersonic solid-state deposition process, Cold Spray (CS) has a unique role among other thermal spray techniques as it uses compressed and heated gas to accelerate particles to a critical velocity. CS can be an expensive process, especially when helium is used as a processing gas. In recent thermal spray developments, High-Velocity Air Fuel (HVAF) has taken a specific place in terms of providing dense and strong coatings similar to CS, but also coatings with less oxidation than High- Velocity Oxy-Fuel (HVOF). In contrast to these techniques, HVAF uses a mixture of fuel and air, instead of pure oxygen as in HVOF, to accelerate particles. Therefore, HVAF appears as a relatively cheaper and environmentally friendly alternative for the deposition of a wide variety of materials. The aim of this research is to produce fully dense copper coatings with limited oxidation using an inner diameter (ID) HVAF system and to compare the microstructure with CS copper coatings. Coating microstructures, surface roughness, and microhardness are studied using different characterization methods such as Scanning Electron Microscopy (SEM). Through this paper, the influence of both spray processes, CS and ID-HVAF, on the deposition of copper coatings is discussed. Cross-sectional studies of different coatings show a fairly dense microstructure for CS and ID-HVAF coatings. Moreover, it is discussed how the copper coating properties can change upon modifying the spray parameters.
The present study reports the green synthesis of cupric oxide nanoparticles (CuO NPs) by an aqueous leaf extract of Moringa oleifera and the antifungal activity assessment of CuO NPs against the phytopathogenic fungi Aspergillus flavus and Aspergillus niger . The CuO NPs showed variable fungitoxic effects against A. flavus and A. niger . At higher doses (1 mg/mL), 83.51 % of mycelial inhibition was found against A. flavus , but 43.51 % was found against A. niger . The percentage inhibition of mycelial growth was found to be dose dependent. The cell viability analysis was carried out to reveal the mechanism of the fungitoxic effect of synthesized NPs and it was revealed that the CuO NPs caused oxidative stress associated with increased ROS production, leading to fungal cell death. The synthesized CuO NPs showed single phase cupric oxide with a monoclinic structure and highly uniform in size (3–5 nm). As the synthesized CuO NPs showed good stability under open atmospheric conditions and a fungitoxicity effect against A. flavus , they may be used to control fungal diseases in an eco‐friendly manner.
Full-text available
The biochemical basis for the essentiality of copper, the adequacy of the dietary copper supply, factors that condition deficiency, and the special conditions of copper nutriture in early infancy are reviewed. New biochemical and crystallographic evidence define copper as being necessary for structural and catalytic properties of cuproenzymes. Mechanisms responsible for the control of cuproprotein gene expression are not known in mammals; however, studies using yeast as a eukaryote model support the existence of a copper-dependent gene regulatory element. Diets in Western countries provide copper below or in the low range of the estimated safe and adequate daily dietary intake. Copper deficiency is usually the consequence of decreased copper stores at birth, inadequate dietary copper intake, poor absorption, elevated requirements induced by rapid growth, or increased copper losses. The most frequent clinical manifestations of copper deficiency are anemia, neutropenia, and bone abnormalities. Recommendations for dietary copper intake and total copper exposure, including that from potable water, should consider that copper is an essential nutrient with potential toxicity if the load exceeds tolerance. A range of safe intakes should be defined for the general population, including a lower safe intake and an upper safe intake, to prevent deficiency as well as toxicity for most of the population.
Full-text available
Escherichia coli O157:H7 is a serious pathogen causing haemorrhagic colitis. It has been responsible for several large-scale outbreaks in recent years. E. coli O157:H7 is able to survive in a range of environments, under various conditions. The risk of infection from contaminated surfaces is recognised, especially due to the low infectious dose required. In this study, a high concentration (107 cells) of E. coli O157 was placed onto different metals and survival time measured. Results showed E. coli O157 to survive for over 28 days at both refrigeration and room temperatures on stainless steel. Copper, in contrast, has strong antibacterial properties (no bacteria can be recovered after only 90 min exposure at 20 °C, increasing to 270 min at 4 °C) but its poor corrosion resistance and durability make it unsuitable for use as a surface material. Other copper-containing alloys, such as copper nickels and copper silvers, have improved durability and anticorrosion properties and greatly reduce bacterial survival times at these two temperatures (after 120 min at 20 °C and 360 min at 4 °C, no E. coli could be detected on a copper nickel with a 73% copper content). Use of a surface material with antibacterial properties could aid in preventing cross-contamination events in food processing and domestic environments, if standard hygiene measures fail.
Full-text available
TiO(2)-coated surfaces are increasingly studied for their ability to inactivate microorganisms. The activity of glass coated with thin films of TiO(2), CuO and hybrid CuO/TiO(2) prepared by atmospheric Chemical Vapour Deposition (Ap-CVD) and TiO(2) prepared by a sol-gel process was investigated using the inactivation of bacteriophage T4 as a model for inactivation of viruses. The chemical oxidising activity was also determined by measuring stearic acid oxidation. The results showed that the rate of inactivation of bacteriophage T4 increased with increasing chemical oxidising activity with the maximum rate obtained on highly active sol-gel preparations. However, these were delicate and easily damaged unlike the Ap-CVD coatings. Inactivation rates were highest on CuO and CuO/TiO(2) which had the lowest chemical oxidising activities. The inactivation of T4 was higher than that of Escherichia coli on low activity surfaces. The combination of photocatalysis and toxicity of copper acted synergistically to inactivate bacteriophage T4 and retained some self-cleaning activity. The presence of phosphate ions slowed inactivation but NaCl had no effect. The results show that TiO(2)/CuO coated surfaces are highly antiviral and may have applications in the food and healthcare industries.
Full-text available
Impregnation or coating of cotton and polyester fibers with cationic copper endows them with potent broad-spectrum antibacterial, antiviral, antifungal, and antimite properties (Borkow, G. and Gabbay, J. (2004). Putting Copper into Action: Copper-impregnated Products with Potent Biocidal Activities, FASEB Jounal, 18(14): 1728-1730). This durable platform technology enables the mass production of woven and non-woven fabrics, such as sheets, pillow covers, gowns, socks, air filters, mattress covers, carpets, etc. without the need of altering any industrial procedures or machinery, but only the introduction of copper oxide-treated fibers. The biocidal properties of fabrics containing 3-10% copper-impregnated fibers are permanent, are not affected by extreme washing conditions, and do not interfere with the manipulation of the final products (e.g., color, press, etc.). In this article, the authors describe data showing that (i) antifungal socks containing 10% w/w (weight/weight) copper-impregnated fibers alleviate athlete’s foot; (ii) antimicrobial fabrics (sheets) containing 10% (w/w) copper-impregnated fibers decrease bacterial colonization in a clinical setting; and (iii) these products do not have skin-sensitizing properties or any other adverse effects. Taken together, these results demonstrate the wide preventive and curative potential of copper oxide-impregnated apparel products.
Full-text available
Copper oxide (CuO) has broad-spectrum anti-microbial and anti-fungal properties. The aim of this study was to test the acaricidal efficacy of CuO-impregnated fabrics on the common house dust mite, Dermatophagoides farinae. The overall vitality/mobility of the mites was reduced when they were exposed to the CuO-impregnated fabrics and, when possible, the dust mites migrated to fabrics where no CuO was present. The mortality of mites exposed for 10 days to fabrics containing 0.2% (w/w) CuO was significantly higher than the mortality of mites on control fabrics (72 ± 4 and 18.9 ± 0.3%, respectively). The mortality reached 95.4 and 100% with fabrics containing 0.4 and 2% CuO after 47 and 5 days, respectively. The acaricidal effect of copper oxide seems to be due to direct toxicity. The use of fabrics containing copper oxide may thus be an important avenue for reducing house dust mite populations, and for reducing the load of dust mite allergens.
This treatise reviews medical uses of various forms of copper recorded throughout the history of mankind. Ancient Egyptian papyri, Greek, Roman, Aztec, Hindu, and Persian writings as well as medieval and subsequent European medical literature record various consistent medical uses of copper. There are many reported uses of copper and its compounds as antibacterial, antiinflammatory, antiarrhythmic, antitumor, and antiepileptic agents. Copper was also recommended to promote wound healing and heal broken bones. Tracing the development of folk medicine and the many rediscoveries of the beneficial effects of copper compounds leads to the suggestion that serious consideration should be given to modern-day medical uses of complexes of this essential metalloelement.
Polychlorinated dibenzo-para-dioxins (PCDDs) are present as trace impurities in various manufactured chemicals and in combustion products. The chemical and environmental stability of PCDDs and their tendency to accumulate in fatty tissues have resulted in their widespread detection throughout the global ecosystem. The most toxic and extensively studied PCDD isomer is 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3,7,8-TCDD). Accidental contamination of the environment by 2,3,7,8-TCDD has resulted in deaths in many species of birds, wildlife, and domestic animals, and in the closing of rivers to fishing due to high residues in fish, i.e., >50 parts per trillion (ppt) wet weight. Laboratory studies with birds, mammals, aquatic organisms, and other species have conclusively demonstrated that exposure to 2,3,7,8-TCDD can be associated with acute and delayed mortality, carcinogenic, teratogenic, reproductive, mutagenic, histopathologic, and immunotoxic effects.