Antimicrobial properties of copper to fight SARS-CoV-2

Ernesto G. Maffia, Micaela D Vignoni *

Prointec I&D, Departamento de Mecánica, Facultad de Ingeniería, La Plata, Universidad
Nacional de La Plata. (UNLP) Argentina.
(*) md.vignoni@gmail.com

Abstract

A new coronavirus, SARS-CoV-2, which emerged in China, has become a global health
problem in a matter of months. The seriousness of the situation is mainly due to the
rapidity of contagion, highlighting the limited response capacity of the emergency services
to a high demand in a short time. One of the health strategies to control contagion in
places with high levels of human circulation should be the use of materials with
recognized antimicrobial capacity, such as copper and its alloys. The objective of this study
is to answer two essential questions: What are the most important mechanisms and
phenomena by which copper is an antimicrobial metal and, consequently, causes the
inactivation of coronaviruses? What actions or measures should be taken regarding the
use of Copper that helps reduce the transmission of SARS-CoV-2? The methodology
adopted for the study is the review of the literature, the period of time selected for the
study is mostly from 2010 to 2020 and the information was consulted from multiple
databases (*)

Results of different studies report that the ability of Copper, as a biocide, is centered on its
redox and complex-forming properties that copper ions possess. These characteristics are
highly detrimental to microorganisms because they participate in a wide spectrum of
interactions with many biomolecules (including lipids, proteins, and nucleic acids).
Damage is produced by the various mechanisms resulting from a direct interaction with
ions of this metal or indirectly due to the generation of reactive oxygen species.

Copper alloys can become a very useful resource not only to control of infections of
coronavirus, but also to help to mitigate the impact of possible future pandemics and in
controlling the spread of new infectious diseases.

Keywords: copper, copper alloys, SARS-CoV-2, antimicrobial properties,

(*) Platforms consulted:

 https://scielo.org/
 https://www.sciencedirect.com
 http://www.asminternational.org/
 https://www.who.int/es
  https://www.researchgate.net/
 https://www.elsevier.com/
 https://www.mdpi.com/journal/materials
 https://www.mdpi.com/journal/microorganisms
 https://www.mdpi.com/journal/ijms
 https://www.nejm.org/
 https://mbio.asm.org/
 https://cmr.asm.org/
 https://aem.asm.org/
 https://pubs.acs.org/

1. Introduction

Modeling of transmission routes has shown that the spread of disease from surfaces
contaminated with pathogens is highly significant [1] [2] [3]. Symptoms of respiratory
diseases cause continuous contamination of surfaces and the persistence of the
coronavirus on them represents a considerable risk of infection if the virus is transferred
to the mouth, nasal mucosa or conjunctiva after having touched a contaminated surface
[4].

Nicas and Best [5] found that people in office settings touched their faces an average of 15
times per hour, providing ample opportunity for the spread of infections. In addition to
the fact that incubation times of between two and ten days, which facilitates community
contagion, either by drops, contaminated hands or surfaces have been described [6] [7].

Although cleaning and disinfection procedures such as hand washing and regular cleaning
with disinfectants are the first protection measure, they are not practical actions to
implement in public places, community spaces and transportation systems with frequent
movement of people, due to assiduity [8]. The implementation of copper then becomes a
powerful tool to combat SARS-CoV-2, as well as helping to mitigate the impact of possible
future pandemics, it also helps to control the spread of new infectious diseases.

Therefore, this study clearly describes the most relevant properties and interactions by
which copper is an antimicrobial metal, also takes into account the structure of the viron
of coronaviruses to understand the phenomena involved in its inactivation.

2. Study methodology adopted

For the development of this study the systematic literature review technique was used.
This is a tool used to collect secondary data for critical evaluation of results and qualitative
or quantitative synthesis of findings. Systematic reviews ask large- or small-scale study
questions, define and synthesize studies that are specifically relevant to the topic of
systematic analysis of existing data.

3. Coronaviruses and their inactivation

Unlike most microorganisms, viruses are obligate intracellular parasites, that is, they
depend on the biochemical machinery of the host cell for their replication [9]. Knowledge
of the structural (size and morphology) and genetic (nucleic acid type and structure)
characteristics of a virus provides information about how it replicates, spreads, and causes
disease [9]. The outer layer of the viron, the complete virus particle [9], is the structure in
charge of transport, protection and packaging during virus transmission, either from one
host to another and for extension within the host to the target cell. In addition, the
proteins adhered to the envelope intervene in the interaction between the virus and the
target cell, taking into account that the initial event in the viral, replication cycle is the
adsorption process by which the specific binding between a molecule present in the cell
membrane, the receptor, and the antireceptor, an external protein of the viron, also
called viral adhesion protein (PAV) [9] [10] is established. Consequently, removal or
alteration of the outer envelope results in inactivation of the virus.

4. Relationship between copper alloys and microorganisms

Metals have different properties that govern their interactions and reactivity with
microorganisms [11]. Although the antimicrobial mechanisms of the copper surface are
known, there are still some points that are not defined. For example, there is still no
consensus among scientists regarding the exact sequence of events that lead to "death or
contact inactivation" [12]. However, the importance of each phenomenon is likely to
depend on the type of microorganism. Literature reports that the redox and complex
formation properties are the main characteristics of copper ions that are highly harmful to
microorganisms because they participate in a wide spectrum of interactions with
biomolecules (including lipids, proteins and nucleic acids) [13] [14]. The damage is
produced by various structures and biochemical reactions resulting from a direct
interaction with the ions of this metal or also indirectly, by generating reactive oxygen
species (ROS); These species (oxygen ions, free radicals and both organic and inorganic
peroxides) constitute a group of free radicals that have the capacity to produce oxidative
damage because they are highly reactive against other species. This characteristic is due
to the fact that they present an unpaired electron, taking into account that elements are
more stable when they present their paired electrons in the orbitals [15]. Different ROS
are presented in Figure 1.
Figure 1. Generation of different reactive oxygen species. Image adapted from Klaus A. et
al. [16].

4.1. Copper Coordination Compounds

Both Cu (I) and Cu (II) show ease for the formation of coordination complexes, in which
the cation and the corresponding ligands act as Lewis acids and bases respectively. The
theory of acids and bases, hard and soft put forward by RG Pearson empirically classifies
Lewis acids and bases according to the stabilities of the complexes they form, resulting in
that hard acids bind to hard bases, just as soft acids bind to soft bases [17]. See Table 1.
Also, while Cu (I) binds with thiol and thioether groups; Cu (II) binds preferentially to
groups that have O and N as electron donor atoms and, in this case, ligands with S are less
frequent [18]. Despite these differences, both ionic species of copper have affinity for
organic ligands present in various proteins. Highlighting the fact that some studies affirm
that, in part, the antimicrobial property is due to its affinity with sulfur [19] [20] [21].

Cell membranes contain macromolecules with highly electronegative chemical groups that
serve as adsorption sites for metal ions [22] [23]. Due to its ability to coordinate metals, it
has been postulated that the cell membrane is a site where some metals exert their
toxicity [24] [25]. Copper ions have a higher affinity for metal binding sites in proteins,
compared to other transition metal ions, (determined by the Irvin-Williams series) and
therefore, if available, prone to coordinate in a variety of non-native biological sites,
replacing the original metals present in biomolecules, and contributing to the
antimicrobial property of copper [14]. This phenomenon is called ionic mimicry or
molecular mimicry, depending on whether metal ions or metal complexes are involved
respectively. The effect of the replacement of native metals can generate conformational
defects of nucleic acids or proteins, altering their functionality [25].

4.2. Oxide reduction

Copper is a transition metal with the following electron configuration [Ar] 3d10 4s1. In
biological systems, copper is part of numerous proteins, being the ions Cu (I) and Cu (II)
the ones that present biochemical relevance [27] [28] and are, in turn, the most frequent,
despite the fact that the oxidation states of this metal range from 0 to +4 [29] [30].

An important characteristic of metals is their ability to participate in oxidation-reduction

reactions [25]. The reduction potential is a thermodynamic parameter that determines the
tendency of a metallic species to acquire electrons from a donor and to reduce itself. The
donor species loses electrons and is oxidized; just as the reduced species is the one that
receives those electrons. Thus, reduction and oxidation always occur simultaneously, and
each individual reaction is called a half-reaction. The two half-reactions are balanced with
respect to the number of electrons they gain or donate, and the net change in electrical
charge can be calculated from the standard electrode potentials of each half-reaction [24].

Copper is the only element of the first series of block d that presents a stable +1 oxidation
state, except in aqueous medium. The relative stability of Cu (I) and Cu (II) in aqueous
solution is determined, mainly, by the following potential values:
+1 −¿⇌Cu s ¿
Cu(aq )+ e Eº = 0,52 V (1)
+1
−¿⇌Cu(aq )¿
Cu +2
(aq )+ e
Eº = 0,153 V (2)

With equations (1) and (2) we can obtain equation (3) of the process of dismutation of Cu
(I) in water and the corresponding equilibrium constant:

2 Cu+1 +2
(aq) ⇌Cu s +Cu (aq) Eº = 0,367 V 6,2
K ≅ 10 (3)

Because K >> 1 means that, in the equilibrium state, reaction (3) shows a strong shift to
the right, which implies low concentrations of Cu (I) ions, with cupric ion being the
predominant ionic species.

Among the proposed mechanisms that provide antimicrobial properties, the copper
dismutation capacity stands out; this is its ability to accept and donate an electron as it
moves between the Cu (I) and Cu (II) oxidation states. This gives rise to the production of
hydroxyl radicals through the Fenton (4) and Haber-Weiss (6) reactions where copper acts
as a catalyst [31]; This can be seen in Figure 2.
+2
−¿+ Cu ¿

H 2 O 2+Cu +¿→ ∙OH + OH ¿

(4)
+2 +¿ ¿
−¿+Cu → O2+ Cu ¿
∙ O2 (5)
−¿+ O2 ¿

∙ O−¿+H
2
2 O2 → ∙OH +OH ¿
(6)
The Fenton reaction occurs by the interaction of cuprous ions with oxidative
intermediates of cellular debris, molecular oxygen, or the virus envelope, thus producing
highly toxic hydroxyl radicals [32].

Figure 2. Scheme of the Haber-Weiss and Fenton reactions with copper as catalyst Image
adapted from [33].

Fujimori et. al. [34] observed the inactivation of the influenza A H1N1 strain (from the
2009 pandemic) by Cu (I) iodide nanoparticles that involved hydroxyl radicals and resulted
in the degradation of the viral proteins hemagglutinin and neuraminidase. They assumed
that, although there was no exogenous hydrogen peroxide to fuel the Fenton reaction, Cu
(I) reacted with molecular oxygen to generate the superoxide anion (equation (7)) and
subsequently form the hydrogen peroxide according to equation (8):
+2 −¿¿
+¿ →Cu +O 2 ¿
O2(aq) +Cu (7)
+ ¿→ H2 O 2 +O 2 ¿
−¿+H ¿
2 O2 (8)

Reactive oxygen species can induce oxidative stress and damage lipids, nucleic acids, and
proteins [35] [36]; mainly the hydroxyl radical, which is such a strongly oxidizing radical
that it can react with practically all biological molecules [37].

The relationship between free radicals and proteins is extraordinarily complex, even so, it
is known that some products such as protein hydroperoxides are generated from the
attacked proteins, which are relatively stable and can generate new radicals when they
react with transition metals [38] , for example, according to reactions (9) and (10) shown
below:

∙ OH + RSH → H 2 O+ RS ∙ (9)

∙ OH + R3 CH → H 2 O+ R3 C ∙ (10)

Another mechanism of action of copper ions has been shown to be the release of iron
resulting from the disruption of coordinated complexes with iron cations, for example
[4Fe-4S] present in some proteins [25] [26]. The iron ions released catalyze, like copper,
the Fenton reaction, leading to generating more radicals [26].
5. Laboratory studies that demonstrate the antimicrobial capacity of Copper

In 1983 Kuhn [39] compared the levels of bacterial contamination found in door knobs,
made of brass and stainless steel, finding a great difference between the two. Almost two
decades later Harold Michels et al. decided to explore this property in the laboratory and
determined a protocol for the assays [40], typically using the S304 stainless steel alloy as
the experimental control unit. Later, Espírito Santo et al. developed a so-called dry
inoculation method that used a smaller inoculum than the previous procedure, which is
considered wet [41]. The dry method improved the conditions of use of the real world
surface [8].

In general, microorganisms are inactivated upon exposure to copper within hours, but
parameters such as inoculation technique, incubation temperature, and copper content of
the alloy used were not systematically investigated, making comparisons difficult. direct
results between different studies, if not impossible. See Table 1.

Table 1. Summary of resistance of some microorganisms to contact with copper. Table

adapted from [26].

Species Application Method Killing Time

6
Salmonella enterica Wet, 4.5 X 10 CFU 4h
Campylobacter jejuni Wet, 4.5 X 106 CFU 8h
Escherichia coli O157 Wet, (3–4) X 107 CFU 65 min
Escherichia coli O157 Wet, 2.7 X 107 CFU 75 min
MRSA (NCTC10442) Wet, (1–1.9) X 107 CFU 45 min
EMRSA-1 (NCTC11939) Wet, (1–1.9) X 107 CFU 60 min
EMRSA-16 (NCTC13143) Wet, (1–1.9) X 105 CFU 90 min
Listeria monocytogenes Scott A Wet, 107 CFU 60 min
Candida albicans Wet, 105 CFU 60 min
Klebsiella pneumoniae Wet, 107 CFU 60 min
Pseudomonas aeruginosa Wet, 107 CFU 3h
Acinetobacter baumannii Wet, 107 CFU 3h
MRSA Wet, 107 CFU 3h
Influenza A virus (H1N1) Wet, 5 X 105 viruses 6h
Clostridium difficile (ATCC 9689) Wet, 2.2 X 105 CFU 24 - 48 h
Clostridium difficile NCTC11204/R20291 Wet, (1-5) X 106 CFU 30 min
Pseudomonas aeruginosa PAO1 Wet, 2.2 X 107 CFU 2h
MRSA NCTC 10442 Wet, 2 X 107 CFU 75 min
Escherichia coli W3110 Dry, 109 CFU 1min
Pantoea stewartii DSM30176 Dry, 109 CFU 1min
Pseudomonas oleovorans DSM 1045 Dry, 109 CFU 1min
Aspergillus flavus Wet, (2–300) X 105 spores 120 h
Aspergillus fumigatus Wet, (2–300) X 105 spores > 120 h
Fusarium culmonium Wet, (2–300) X 105 spores 24 h
Fusarium oxysporum Wet, (2–300) X 105 spores 24 h
Fusarium solani Wet, (2–300) X 105 spores 24 h
Penicillium crysogenum Wet, (2–300) X 105 spores 24 h
Candida albicans Wet, (2–300) X 105 spores 24 h
Enterococcus hirae ATCC 9790 Wet, 107 CFU 90 min
Different Enterococcus spp. Wet, 106 CFU 60 min
Candida albicans Dry, 106 CFU 5 min
Saccharomyces cerevisiae Dry, 106 CFU < 1 min

However, some general principles seem clear: higher copper content of alloys [40], higher
temperature [42] and higher relative humidity [43] increase the effectiveness of contact
removal. In contrast, treatments that reduce the rate of corrosion, such as the application
of corrosion inhibitors or a thick layer of copper oxide, decrease the antimicrobial
effectiveness of copper surfaces [44]. In addition to the microorganisms listed in Table 2,
copper surfaces and their alloys have demonstrated their antimicrobial effect against a
wide variety of other microbes including viruses, fungi, bacteria, with more being likely to
be added as researchers explore the potential of copper alloy surfaces to control infection
in healthcare facilities, schools and other public spaces and antimicrobial properties
become more widely known. The case of Deinococcus radiodurans is particularly
noteworthy, a bacterial species highly resistant to ionizing radiation, desiccation, oxidizing
and electrophilic agents, which presents a similar degree of sensitivity to exposure to
copper alloy surfaces than others. [41] [45].

Studies of viral sensitivity to copper alloy surfaces are still in the early stages of research,
their kinetics and inactivation mechanism are not well studied, also highlighting that only
a few viruses have been tested and they are divided into very different groups according
to their capsid type [8]. To determine whether the wide range of inactivation kinetics
exhibited by different viruses is a function of capsid or genome structure, studies would
have to be carried out with a larger group of related viruses using a single protocol [8]

5.1. Stability of coronaviruses on different surfaces

In a study by Warnes et al. [32] published in 2015, the inactivation of the human
coronavirus HCoV-229E is evaluated on surfaces of different materials, including
polytetrafluoroethylene (PTFE, also called Teflon), polyvinyl chloride (PVC), ceramic tiles,
glass, silicone rubber, stainless steel, copper, cupro-nickel and brass. The researchers
showed that this coronavirus remains active for several days on surfaces of common non-
biocidal materials and they emphasize that the inactivation resulting from contact with
copper is not only rapid, but is accompanied by massive structural damage to the viron
and irreversible destruction of the material. viral genetics [32]. On the other hand, Warnes
et al. demonstrated that copper ions and the generation of reactive oxygen species are
involved, either directly or indirectly, in the inactivation of HCoV-229E on copper surfaces
and copper alloys. In this case, they evaluated the inactivation of the virus on copper and
brass surfaces (70% copper), in the presence of ethylenediaminetetraacetic acid (also
called EDTA) and batocuproin disulfonate (BCS), which are chelating agents for Cu (II) and
Cu (I) ions respectively.

A recent study by Van Doremalen et al. [46] published in "The New England Journal of
Medicine" deserves a mention in this review. Investigators evaluated the stability of SARS-
CoV-2 on various surfaces and compared it to the stability of the coronavirus with which it
is most closely related, SARS-CoV-1 [47]. In the test they evaluated four surfaces: plastic,
stainless steel, copper and cardboard. As a result, they obtained that SARS-CoV-2 was
more stable in plastic and stainless steel than in copper and cardboard. With the
estimated half-life of SARS-CoV-2 being approximately 5.6 hours in stainless steel and 6.8
hours in plastic, compared to the half-life in contact with copper, which is below 2 hours
for both coronaviruses [ 46]. Some scientists believe that the differences in inactivation
times between the studies by Warnes et al. [32] and Van Doremalen et al. [46] are mainly
due to the fact that in each case they resorted to different techniques in the experimental
protocols. Although they were carried out with different viruses, it is unlikely that it is the
source of the observed differences because the inactivating property of copper extends to
all coronaviruses because this class of viruses are, in essence, structurally identical; which
is why it can be assumed that the efficacy of copper alloys against Hu-CoV-229E should
also be observed when testing with the rest of the coronaviruses.

6. The health of population and copper

Ancient civilizations were taking advantage of copper's antimicrobial properties long

before Louis Pasteur identified bacteria as disease-causing microorganisms. An example of
this is the case of an ancient Hindu tradition (more than 3,000 years old) that
recommends collecting and storing household water supplies in copper containers to
improve health. Recent studies confirm that overnight storage of contaminated water in
copper containers kills bacterial contaminants and makes the water safe to drink [8] [48]
[49]. Colonists in North America dumped silver coins into shipping containers to conserve
water, wine, milk, and vinegar, and Japanese soldiers used a similar strategy during World
War II to prevent the spread of dysentery. [50] [51]. One aspect to be highlighted is the
efficacy of copper in typical conditions of humidity and temperature in indoor
environments, which is much higher than that of other possible antimicrobial surfaces,
such as silver, under the same conditions [52] [43]. Since copper has been present in the
daily use elements of different civilizations for centuries [43], there are no records of
microorganisms that have developed sufficient resistance against the toxicity of this metal
[8]. Researchers consider that the hereditary mutations necessary for microorganisms to
develop this resistance is not only highly unlikely, but also unfeasible because it hinders
the survival of the organism [8] [53].

In 2008 the United States Environmental Protection Agency (EPA) approved the
registration of around 300 copper alloys as antimicrobial, at which point the study of the
biocidal properties of copper highlighted and began to take importance. Currently there
are more than 500 registered alloys classified into six groups. In all of them, copper is the
majority element (at least 60% by weight) and they must have lead, arsenic and chromium
contents below 0.09% by weight. The EPA strongly emphasizes that the use of these alloys
is a complement to and should not substitute for cleaning and disinfecting practices for
surfaces [54]. There are several studies that support this question, among them, Warnes
and Keevil [52] highlight in their results that the presence of certain polluting substances
can inhibit the access of copper ions to pathogens, affecting the efficiency of the copper
surface as biocidal surface. Also, previous studies found that in contaminated copper
coins, blood, pus, and natural dirt delayed the copper-killing mechanism, presumably due
to chelating action [55] [56]. It is important to avoid the use of products that contain
copper ion chelators, such as EDTA, because these partially and temporarily inhibit the
antimicrobial action. Rather, a good practice is to choose those cleaning and disinfection
products that work synergistically with copper alloys. In the case of viruses, disinfectant
agents weaken viral capsids and decrease inactivation time [6].

7. Copper applications in daily life

Copper can be incorporated into different areas of daily life, adapting to each particular
situation and in different ways [57], [54]. The application of thin copper coatings is
presented as an alternative [58]. Several electrochemical, plasma-based methods are also
available, including: plasma spray, arc spray, and cold spray [59] [60] [61] [62] [63] [64]. In
a study [59] they recorded that the use of these three techniques gives biocidal properties
to stainless steel substrates, but not with the same efficiency; concluding that it depends
on the ease of diffusion of copper ions towards the surface. Likewise, another notable
application is the use of this metal in paints. In fact, there are currently on the market
coatings for boat hulls that use copper-based additives to prevent the adherence of
microorganisms and crustaceans [49] [65] [66].

Nanotechnology can also take advantage of the antimicrobial properties of copper. In this
case, the properties of different nanoparticles are studied, including those of copper oxide
(CuONPs) [31] [25] [52]. The metallic nanoparticles (NPs) can be simple or compound and
of sizes between 1 to 100 nm; metallic nanomaterials (particularly those made of copper
and silver) can have strong antimicrobial properties [67] [68] [69]. A surprising capacity
recorded for many NPs is their ability to physically interact with the cell surfaces of some
bacteria [68] [70] [71]. In the case of NPs, the efficiency of biocidal activity is influenced by
several attributes that control the release of metal ions and those that are specific to the
particle, mainly size [72], shape [73], charge surface [74] and composition [25]. The
mechanism of action has also been associated with the generation of reactive oxygen
species [75] [76] and damage to the plasma membrane [68] [70] [73] [24].

An increasing number of studies indicate that ion release is crucial in the efficiency of
antimicrobial nanoparticles [75] [77] [78]. Silver NPs synthesized and preserved in
anaerobic chambers do not oxidize and, therefore, do not release ions; circumstances in
which Ag nanoparticles of all sizes did not demonstrate biocidal activity [78]. In contrast,
other investigators have found that the leaching of copper oxide metal complexes by
bacterial amino acids is necessary for its antimicrobial toxicity [75]. Strategically
engineered nanoparticles, in which the release of ions is controlled or targeted to specific
bacterial cells, have numerous antimicrobial applications and access a global market for
nanoparticles in biotechnology and pharmaceuticals, valued at $ 17.5 billion in 2011 [79].

One aspect to highlight about NPs is their ability to be integrated into polymeric matrices.
Among the advantages of the development of composite materials is the wide spectrum
of properties that can be covered. In the particular case, polymeric matrices with copper
nanoparticles emerge as a way to expand the applications of biocidal metals that becomes
even more relevant when contemplating the constant growth of the polymer market. This
growth is due to its properties such as: chemical, radiation and heat resistance, rigidity,
clarity, barrier behavior for gases and liquids, impact, flexibility and moderate cost [25]
[80]. For example, polypropylene products are widely used in medical devices, packaging
products, and delivery systems for solid and liquid pharmaceuticals [80].

Continuing with composite materials, one of the new technological platforms for the use
of antimicrobial copper is its use in textile fibers, as well as in latex, nylon, cotton, among
others, which are also polymeric products [25] [81] [82]. This is very advantageous for the
design of clothing mainly for health center staff (both those who work there and for
patients), bedding, chinstraps, gloves, to name a few examples.
8. Conclusions

In this review, an investigation based on the recent literature regarding the mechanisms
and phenomena by which copper is an antimicrobial metal and, consequently, produces
the inactivation of coronaviruses is carried out. Actions regarding the use of Copper that
help reduce the transmission of SARS-CoV-2 have been taken and also analyzed.

The most significant topics of the review are shown below

• The biocidal activity of copper focuses on two main properties, its ease of complex
formation and its redox properties. The ions of this metal are highly damaging to
microorganisms due to their interactions with various molecules, such as lipids,
proteins and nucleic acids. The damage is generated both by mechanisms resulting
from a direct interaction with this metal ions, and indirectly due to the generation of
reactive oxygen species.
• Regarding the formation of coordination complexes, both Cu (I) and Cu (II) ions are easy
to form and both ionic species show affinity with organic ligands present in various
proteins. Therefore, they are prone to coordinate in non-native sites contributing to
the antimicrobial property of copper. Added to this, the virus membrane presents
macromolecules with highly electronegative chemical groups that serve as adsorption
sites for these ions.
• On the other hand, due to the oxido-reduction capacity of copper ions, one of the
phenomena that stands out is the generation of ROS, indicating the hydroxyl radical,
strongly oxidizing, which reacts with practically all biological molecules. ROS, together
with the action of copper ions, generate oxidative stress that damages the envelope
and viral RNA.
• The mechanism that acts with the greatest speed is related to the action of ions and,
secondly, to reactive oxygen species, emphasizing that, by reducing the copper content
of the alloy, ROS take a greater role in inactivation. The fact that the inactivation of this
virus results from morphological changes accompanied by irreversible damage due to
the destruction of the viral genome is also emphasized.

Bearing in mind the resurgence of old diseases, together with the appearance of new
diseases (such as Covid-19), and the generalized resistance to antibiotics, the therapeutic
options against bacterial pathogens are reduced; This, added to the increase in the
immunocompromised population, has required prevention strategies to control infections.
Unfortunately, it is a utopia to seek the eradication of nosocomial infections, it is an
inherent risk of staying in a hospital or health center. However, it means that measures to
reduce the number of infections must be improved, continuously allocating resources and
efforts focused on the search for new prevention methods, knowing that the higher the
microbial load the possibility of contracting a disease is favored.

Bibliography

[1] A. R. Fehr and S. Perlman, "Coronaviruses: An Overview of Their Replication and

Pathogenesis," Methods in Molecular Biology, vol. 1282, pp. 1-23, 2015. DOI:
10.1007/978-1-4939-2438-7_1

[2] C. Ogimi, Y. J. Kim, E. T. Martin, H. J. Huh, C. H. Chiu and J. A. Englund, "What’s New
With the Old Coronaviruses?," Journal of the Pediatric Infectious Diseases Society, vol. 9,
no. 2, p. 210–217, 2020. DOI: 10.1093/jpids/piaa037

[3] J. M. van den Brand, S. L. Smits and B. L. Haagmans, "Pathogenesis of Middle East
respiratory syndrome coronavirus," The Journal of Pathology, vol. 235, no. 2, pp. 175-84,
2015. DOI: 10.1002/path.4458

[4] B. A. Wevers and L. van der Hoek, "Recently discovered human coronaviruses,"
Clinics in laboratory medicine, vol. 29, no. 4, pp. 715-724, 2009. DOI:
10.1016/j.cll.2009.07.007

[5] J. A. Englund, Y. J. Kim and K. McIntosh, "Human Coronaviruses, Including Middle

East Respiratory Syndrome Coronavirus," in Feigin and Cherry's Textbook of Pediatric
Infectious Diseases, 8 ed., Elsevier, 2019.

[6] World Health Organization, "Origin of SARS-CoV-2 (26 March 2020)," 2020,
reference number: WHO/2019-nCoV/FAQ/Virus_origin/2020.1.
https://apps.who.int/iris/handle/10665/332197 (accessed 12 July 2020).

[7] J. A. Otter, S. Yezli, J. A. Salkeld and G. L. French, "Evidence that contaminated

surfaces contribute to the transmission of hospital pathogens and an overview of
strategies to address contaminated surfaces in hospital settings," American journal of
infection control, vol. 41, no. 5, pp. S6-S11, 2013. DOI: 10.1016/j.ajic.2012.12.004

[8] J. A. Otter, C. Donskey, S. Yezli, S. Douthwaite, S. D. Goldenberg and D. J. Weber,

"Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings:
the possible role of dry surface contamination," Journal of Hospital Infection, vol. 92, no.
3, pp. 235-250, 2016. DOI: 10.1016/j.jhin.2015.08.027

[9] S. F. Dowell, J. M. Simmerman, D. D. Erdman, J. S. J. Wu, A. Chaovavanich, M. Javadi,

Y. J. Yang, L. J. Anderson, S. Tong and M. S. Ho, "Severe Acute Respiratory Syndrome
Coronavirus on Hospital Surfaces," Clinical Infectious Diseases, vol. 39, no. 5, pp. 652-657,
2004. DOI: 10.1086/422652
[10] M. E. El Zowalaty and J. D. Järhult, "From SARS to COVID-19: A previously unknown
SARS-CoV-2 virus of pandemic potential infecting humans–Call for a One Health
approach," One Health, vol. 9, no. 100124, 2020. DOI: 10.1016/j.onehlt.2020.100124

[11] M. Nicas and D. Best, "A Study Quantifying the Hand-to-Face Contact Rate and Its
Potential Application to Predicting Respiratory Tract Infection," Journal of Occupational
and Environmental Hygiene, vol. 5, no. 6, pp. 347-352, 2008. DOI:
10.1080/15459620802003896

[12] G. Kampf, D. Todt, S. Pfaender and E. Steinmann, "Persistence of coronaviruses on

inanimate surfaces and their inactivation with biocidal agents," Journal of Hospital
Infection, vol. 104, no. 3, pp. 246-251, 2020. DOI: 10.1016/j.jhin.2020.01.022

[13] M. Zambon, "Influenza and other emerging respiratory viruses," Medicine, vol. 42,
no. 1, pp. 45-51, 2014. DOI: 10.1016/j.mpmed.2013.10.017

[14] H. T. Michels and C. A. Michels, "Copper alloys-The new ‘old’ weapon in the fight
against infectious disease," Microbiology, vol. 10, p. 23, 2016.

[15] S. Warnes, Z. R. Little and C. W. Keevil, "Human Coronavirus 229E Remains Infectious
on Common Touch Surface Materials," MBio, vol. 6, no. 6, p. 10, 2015. DOI:
10.1128/AEM.00597-11

[16] R. Hong, T. Y. Kang, C. A. Michels and N. Gadura, "Membrane Lipid Peroxidation in

Copper Alloy-Mediated Contact Killing of Escherichia coli," Applied and environmental
microbiology, vol. 78, no. 6, pp. 1776-1784, 2012. DOI: 10.1128/AEM.07068-11

[17] P. R. Murray, K. S. Rosenthal and M. A. Pfaller, Microbiología Médica, 8th ed. ed.,
Elsevier Health Sciences, 2017. ISBN: 9788491130765

[18] J. A. Basualdo, C. E. Coto and R. A. Torres, Microbiología biomédica: bacteriología,

micología, virología, parasitología-inmunología. 2da ed., Atlante Argentina, 2006. ISBN:
9789509539471

[19] K. L. Haas and K. J. Franz, "Application of Metal Coordination Chemistry to Explore

and Manipulate Cell Biology," Chemical reviews, vol. 109, no. 10, pp. 4921-4960, 2009.
DOI: 10.1021/cr900134a

[20] M. Vincent, R. E. Duval, P. Hartemann and M. Engels-Deutsch, "Contact killing and

antimicrobial properties of copper," Journal of Applied Microbiology, vol. 124, pp. 1032-
1046, 2017. DOI: 10.1111/jam.13681

[21] J. J. Martínez Medina, "Síntesis, caracterización fisicoquímica, determinaciones

biológicas (in vitro) y estudios teóricos de complejos de Cu(II) y VO(IV) con ligandos
antioxidantes y/o antimicrobianos," Disertación doctoral no publicada, Universidad
Nacional de La Plata, 2018.
[22] A. G. Dalecki, C. L. Crawford and F. Wolschendorf, "Copper and Antibiotics:
Discovery, Modes of Action, and Opportunities for Medicinal Applications," Advances in
microbial physiology, vol. 70, pp. 193-260, 2017. DOI: 10.1016/bs.ampbs.2017.01.007

[23] C. C. Carvajal, "Especies reactivas del oxígeno: formación, funcion y estrés

oxidativo," Medicina Legal de Costa Rica, vol. 36, no. 1, pp. 91-100, 2019. ISSN 2215-5287

[24] M. Konigsberg-Fainstein, Radicales libres y estrés oxidativo: Aplicaciones médicas,

México D. F.: Manual Moderno, 2008. ISBN 978-970-729-321-2

[25] P. Atkins, T. Overton, J. Rourke, M. Weller and F. Armstrong, Shriver & Atkins,
Inorganic Chemistry, 4th Ed., Oxford University Press, 2006.

[26] J. A. McCleverty and T. J. Meyer, Comprehensive Coordination Chemistry II, from

biology to nanotechnology. Vol. 6, Elsevier Science, 2004.

[27] M. L. Workentine, J. J. Harrison, P. U. Stenroos, H. Ceri and R. J. Turner,

"Pseudomonas fluorescens’ view of the periodic table," Environmental Microbiology, vol.
10, no. 1, pp. 238-250, 2008. DOI: 10.1111/j.1462-2920.2007.01448.x

[28] D. H. Nies, "Efflux-mediated heavy metal resistance in prokaryotes," FEMS

microbiology reviews, vol. 27, no. 2-3, pp. 313-339, 2003. DOI: 10.1016/S0168-
6445(03)00048-2

[29] J. J. Harrison, H. Ceri and R. J. Turner, "Multimetal resistance and tolerance in

microbial biofilms," Nature reviews. Microbiology, vol. 5, no. 12, p. 928–938, 2007. DOI:
10.1038/nrmicro1774

[30] P. Parikh, D. Zala and B. A. Makwana, "Biosynthesis of Copper Nanoparticles and

Their Antimicrobial Activity," Inst Post Studies Res KSV Uni. India, pp. 1-15, 2014. DOI:
10.4236/oalib.preprints.1200067

[31] A. Parra, M. Toro, R. Jacob, P. Navarrete, M. Troncoso, G. Figueroa and A. Reyes-

Jara, "Antimicrobial effect of copper surfaces on bacteria isolated from poultry meat,"
Brazilian journal of microbiology, vol. 49, no. 1, pp. 113-118, 2018. DOI:
10.1016/j.bjm.2018.06.008

[32] J. A. Lemire, J. J. Harrison and R. J. Turner, "Antimicrobial activity of metals:

mechanisms, molecular targets and applications," Nature Reviews Microbiology, vol. 11, p.
371–384, 2013. DOI: 10.1038/nrmicro3028

[33] H. Palza, "Antimicrobial polymers with metal nanoparticles," International journal of

molecular sciences, vol. 16, no. 1, pp. 2099-2116, 2015. DOI: 10.3390/ijms16012099v
[34] G. Grass, C. Rensing and M. Solioz, "Metallic Copper as an Antimicrobial Surface,"
Applied and environmental microbiology, vol. 77, no. 5, pp. 1541-1547, 2011. DOI:
10.1128/AEM.02766-10

[35] M. Vallet, J. Faus, E. García-España and J. Moratal, Introducción a la Química

Bioinorgánica, Madrid: Editorial Síntesis, 2003.

[36] W. Kaim, B. Schwederski and A. Klein, Bioinorganic Chemistry: Inorganic Elements in

the Chemistry of Life: An Introduction and Guide, John Wiley & Sons, 2013.

[37] C. Housecroft and A. G. Sharpe, Inorganic Chemistry, Pearson Prentice Hall, 2005.

[38] L. Beyer and V. Fernández Herrero, Química Inorgánica, Barcelona: Ariel Ciencia,
2000.

[39] T. Ishida, "Antiviral Activities of Cu(2+) Ions in Viral Prevention, Replication, RNA
Degradation, and for Antiviral Efficacies of Lytic Virus, ROS-Mediated Virus, Copper
Chelation," World Scientific News, vol. 99, pp. 148-168, 2018.

[40] C. Boonla, "Oxidative Stress in Urolithiasis”, in Reactive Oxygen Species (ROS) in

Living Cells, InTech Open Science, 2018, pp. 129-159. DOI: 10.5772/intechopen.75366

[41] Y. Fujimori, T. Sato, T. Hayata, T. Nagao, M. Nakayama, T. Nakayama, R. Sugamata

and K. Suzuki, "Novel antiviral characteristics of nanosized copper(I) iodide particles
showing inactivation activity against 2009 pandemic H1N1 influenza viruS," Applied and
Environmental Microbiology, vol. 78, pp. 951-955, 2012. DOI: 10.1128/AEM.06284-11

[42] S. Shleeva, J. Tkac, A. Christenson, T. Ruzgas, A. Yaropolov, J. Whittaker and L.

Gorton, "Direct electron transfer between copper-containing proteins and electrodes,"
Biosensors & bioelectronics, vol. 20, no. 12, pp. 2517-2554, 2005. DOI:
10.1016/j.bios.2004.10.003

[43] S. Prabhu and E. K. Poulose, "Silver nanoparticles: Mechanism of antimicrobial

action, synthesis, medical applications, and toxicity effects," International nano letters,
vol. 2, no. 1, p. 32, 2012. DOI: 10.1186/2228-5326-2-32

[44] G. Buettner and B. Jurkiewicz, "Catalytic metals, ascorbate and free radicals:
Combinations to avoid," Radiation research, vol. 145, no. 5, pp. 532-541, 1996. DOI:
10.2307/3579271

[45] A. Vicedo Tomey and Y. Vicedo Ortega, "Relaciones del estrés oxidativo con el
catabolismo de proteínas," Revista Cubana de Investigaciones Biomédicas, vol. 19, no. 3,
pp. 206-212, 2000. ISSN 0864-0300.

[46] P. J. Kuhn, "Doorknobs: a source of nosocomial infection?," Diagnostic Medicine, vol.

6, no. 8, pp. 62-63, 1983.
[47] S. A. Wilks, H. T. Michels and C. W. Keevil, "The survival of Escherichia coli O157 on a
range of metal surfaces.," International Journal of Food Microbiology, vol. 105, no. 3, pp.
445-454, 2005. DOI: 10.1016/j.ijfoodmicro.2005.04.021

[48] C. Espírito Santo, E. W. Lam, C. G. Elowsky, D. Quaranta, D. W. Domaille, E. W. Lam,

C. G. Elowsky, D. Quaranta, D. W. Domaille, C. J. Chang and G. Grass, "Bacterial killing by
dry metallic copper surfaces," Applied and environmental microbiology, vol. 77, no. 3, pp.
794-802, 2011. DOI: 10.1128/AEM.01599-10

[49] J. Elguindi, J. Wagner and C. Rensing., "Genes involved in copper resistance influence
survival of Pseudomonas aeruginosa on copper surfaces.," Journal of applied
microbiology, vol. 106, no. 5, pp. 1448-1455, 2009. DOI: 10.1111/j.1365-
2672.2009.04148.x

[50] H. T. Michels, J. O. Noyce and C. W. Keevil., "Effects of temperature and humidity on

the efficacy of methicillin-resistant Staphylococcus aureus challenged antimicrobial
materials containing silver and copper," Letters in Applied Microbiology, vol. 49, no. 2, pp.
191-195, 2009. DOI: 10.1111/j.1472-765X.2009.02637.x

[51] J. Elguindi, S. Moffitt, H. Hasman, C. Andrade, S. Raghavan and C. Rensing, "Metallic

copper corrosion rates, moisture content, and growth medium influence survival of
copper-resistant bacteria.," Applied microbiology and biotechnology, vol. 89, no. 6, pp.
1963-1970, 2011. DOI: 10.1007/s00253-010-2980-x

[52] M. J. Daly, "A new perspective on radiation resistance based on Deinococcus

radiodurans," Nature Reviews Microbiology, vol. 7, no. 3, pp. 237-245, 2009. DOI:
10.1038/nrmicro2073

[53] N. Van Doremalen, T. Bushmaker, D. H. Morris, M. G. Holbrook, A. Gamble, B. N.

Williamson, A. Tamin, J. Harcourt, N. J. Thornburg, S. I. Gerber, J. O. Lloyd-Smith, E. Wit
and V. J. Munster, "Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-
CoV-1," New England Journal of Medicine, vol. 382, no. 16, pp. 1564-1567, 2020. DOI:
10.1056/NEJMc2004973

[54] A. Wu, Y. Peng, B. Huang, X. Ding, X. Wang, P. Niu, J. Meng, Z. Zhu, Z. Zhang, J. Wang,
J. Sheng, L. Quan, Z. Xia, W. Tan, G. Cheng and T. Jiang, "Genome Composition and
Divergence of the Novel Coronavirus (2019-nCoV) Originating in China," Cell Host &
Microbe, vol. 27, no. 3, pp. 325-328, 2020. DOI: 10.1016/j.chom.2020.02.001

[55] B. P. V. Sudha, S. Ganesan, G. P. Pazhani, T. Ramamurthy, G. B. Nair and P.

Venkatasubramanian, "Storing drinking-water in copper pots kills contaminating
diarrhoeagenic bacteria," Journal of Health, Population, and Nutrition, vol. 30, no. 1, pp.
17-21, 2012. DOI: 10.3329/jhpn.v30i1.11271
[56] V. J. Prado, R. A. Vidal and D. T. Claudia, "Aplicación de la capacidad bactericida del
cobre en la práctica médica," Revista médica de Chile, vol. 140, no. 10, pp. 1325-1332,
2012. DOI: 10.4067/S0034-98872012001000014

[57] J. W. Alexander, "History of the medical use of silver," Surgical Infections, vol. 10, no.
3, pp. 289-292, 2009. DOI: 10.1089/sur.2008.9941

[58] G. Borkow and J. Gabbay, "Copper, an ancient remedy returning to fight microbial,
fungal and viral infections," Current Chemical Biology, vol. 3, no. 3, pp. 272-278, 2009.
DOI: 10.2174/187231309789054887

[59] S. L. Warnes and C. W. Keevil, "Mechanism of copper surface toxicity in vancomycin-

resistant enterococci following wet or dry surface contact," Applied and Environmental
Microbiology, vol. 77, no. 17, pp. 6049-6059, 2011. DOI: 10.1128/AEM.00597-11

[60] United States Environmental Protection Agency, "Antimicrcobial Copper Alloys -

Group I and Associated Fabricated Products Master Label," Reg. No. 82012-1, 2014.
https://pdf4pro.com/cdn/united-states-environmental-protection-959a6.pdf (accessed 12
July 2020).

[61] C. E. Espirito Santo, P. V. Morais and G. Grass, "Isolation and characterization of

bacteria resistant to metallic copper surfaces," Applied and environmental microbiology,
vol. 76, no. 5, pp. 1341-1348, 2010. DOI: 10.1128/AEM.01952-09

[62] O. Tolba, A. Loughrey, C. E. Goldsmith, B. C. Millar, P. J. Rooney and J. E. Moore,

"Survival of epidemic strains of nosocomial- and community-acquired methicillin-resistant
Staphylococcus aureus on coins," American journal of infection control, vol. 35, no. 5, pp.
342-346, 2007. DOI: 10.1016/j.ajic.2006.10.015

[63] Z. Ibrahim, A. J. Petrusan, P. Hooke and S. M. Hinsa-Leasure, "Reduction of bacterial

burden by copper alloys on high-touch athletic center surfaces," American journal of
infection control, vol. 46, no. 2, pp. 197-201, 2018. DOI: 10.1016/j.ajic.2017.08.028

[64] D. A. Montero, C. Arellano, M. Pardo, R. Vera, R. Gálvez, M. Cifuentes, M. A.

Berasain, M. Gómez, C. Ramírez and R. M. Vidal, "Antimicrobial properties of a novel
copper- based composite coating with potential for use in healthcare facilities,"
Antimicrobial Resistance and Infection Control, vol. 8, no. 3, 2019. DOI: 10.1186/s13756-
018-0456-4

[65] V. K. Champagne and D. J. Helfritch, "A demonstration of the antimicrobial

effectiveness of various copper surfaces," Journal of Biological Engineering, vol. 7, no. 8,
2013. DOI: 10.1186/1754-1611-7-8

[66] W. Zhang, Y. Zhang, J. Ji, J. Zhao, Q. Yan and P. Chu, "Antimicrobial properties of
copper plasma-modified polyethylene.," Polymer, vol. 47, pp. 7441-7445, 2006. DOI:
10.1016/j.polymer.2006.08.057
[67] S. Cometa, R. Iatta, M. Ricci, C. Ferretti and E. de Giglio, "Analytical characterization
and antimicrobial properties of novel copper nanoparticles-loaded electrosynthesised
hydrogel coatings.," Journal of Bioactive and Compatible Polymers, vol. 28, no. 5, pp. 508-
522, 2013. DOI: 10.1177/0883911513498960

[68] F. Pishbin, V. Mouriño, J. Gilchrist, D. McComb, S. Kreppel, V. Salih, M. Ryan and A.

Boccaccini, "Single-step electrochemical deposition of antimicrobial orthopaedic coatings
based on a bioactive glass/chitosan/nano-silver composite system.," Acta biomaterialia,
vol. 9, no. 7, pp. 7469-7479, 2013. DOI: 10.1016/j.actbio.2013.03.006

[69] V. Kumar, C. Jolivalt, J. Pulpytel, R. Jafari and F. Arefi-Khonsari, "Development of

silver nanoparticle loaded antibacterial polymer mesh using plasma polymerization
process," Journal of Biomedical Materials Research, vol. 101, no. 4, pp. 1121-1132, 2013.
DOI: 10.1002/jbm.a.34419

[70] E. De Giglio, D. Cafagna, S. Cometa, A. Allegretta, A. Pedico, L. Giannossa, L.

Sabbatini, M. Mattioli-Belmonte and R. Iatta, "An innovative, easily fabricated, silver
nanoparticle-based titanium implant coating: Development and analytical
characterization," vol. 405, pp. 805-816, 2013. DOI: 10.1007/s00216-012-6293-z

[71] M. A. Champ, "The Need for the Formation of an Independent," Marine Pollution
Bulletin, vol. 38, no. 4, pp. 239-246, 1999. DOI:10.1016/S0025-326X(98)90196-5

[72] T. Vance, A. Yunnie and C. Zanghí, "Marine Coating Testing Five Years in a Tidal
Stream - Final Report Coppercoat (PMA 139)," Marzo 2018. https://www.fleiss-
yachtzubehoer.de/media/Coppercoat%20Refernzbilder/5%20Jahres%20Test/PMA139-
Final-Report-Coppercoat_March.pdf [Accessed 10 August 2020].

[73] I. Sondi and B. Salopek-Sondi, "Silver nanoparticles as antimicrobial agent: a case

study on E. coli as a model for Gram-negative bacteria," Journal of colloid and interface
science, vol. 275, no. 1, pp. 177-182, 2004. DOI: 10.1016/j.jcis.2004.02.012

[74] P. K. Stoimenov, R. L. Klinger, G. L. Marchin and K. J. Klabunde, "Metal Oxide

Nanoparticles as Bactericidal Agents," Langmuir, vol. 18, no. 17, pp. 6679-6686, 2002. DOI:
10.1021%2Fla0202374

[75] J. P. Ruparelia, A. K. Chatterjee, S. P. Duttagupta and S. Mukherji, "Strain specificity

in antimicrobial activity of silver and copper nanoparticles," Acta Biomaterialia, vol. 4, no.
3, pp. 707-716, 2008. DOI: 10.1016/j.actbio.2007.11.006

[76] S. Bandyopadhyay, J. R. Peralta-Videa, G. Plascencia-Villa, M. Jose-Yacaman and J. L.

Gardea-Torresdey, "Comparative toxicity assessment of CeO2 and ZnO nanoparticles
towards Sinorhizobium meliloti, a symbiotic alfalfa associated bacterium: use of advanced
microscopic and spectroscopic techniques," Journal of hazardous materials, Vols. 241-241,
p. 379–386, 2012. DOI: 10.1016/j.jhazmat.2012.09.056
[77] B. Luef, S. C. Fakra, R. Csencsits, K. C. Wrighton, K. H. Williams, M. J. Wilkins, K. H.
Downing, P. E. Long, L. R. Comolli and J. F. Banfield, "Iron-reducing bacteria accumulate
ferric oxyhydroxide nanoparticle aggregates that may support planktonic growth," The
ISME journal, vol. 7, no. 2, pp. 338-350, 2013. DOI: 10.1038/ismej.2012.103

[78] J. R. Morones, J. L. Elechiguerra, A. Camacho, K. Holt, J. B. Kouri, J. T. Ramírez and M.

J. Yacaman, "The bactericidal effect of silver nanoparticles," Nanotechnology, vol. 16, no.
10, pp. 2346-2353, 2005. DOI: 10.1088/0957-4484/16/10/059

[79] S. Pal, Y. K. Tak and J. M. Song, "Does the antibacterial activity of silver nanoparticles
depend on the shape of the nanoparticle? A study of the Gram-negative bacterium
Escherichia coli," Applied and environmental microbiology, vol. 73, no. 6, pp. 1712-1720,
2007. DOI: 10.1128/AEM.02218-06

[80] A. M. El Badawy, R. G. Silva, B. Morris, K. G. Scheckel, M. T. Suidan and T. M.

Tolaymat, "Surface charge-dependent toxicity of silver nanoparticles," Environmental
science & technology, vol. 45, no. 1, pp. 283-287, 2011. DOI: 10.1021/es1034188

[81] C. Gunawan, W. Y. Teoh, C. P. Marquis and R. Amal, "Cytotoxic origin of copper(II)

oxide nanoparticles: comparative studies with micron-sized particles, leachate, and metal
salts," ACS Nano, vol. 5, no. 9, pp. 7214-7225, 2011. DOI: 10.1021/nn2020248

[82] G. Applerot, J. Lellouche, A. Lipovsky, Y. Nitzan, R. Lubart, A. Gedanken and E. Banin,

"Understanding the antibacterial mechanism of CuO nanoparticles: revealing the route of
induced oxidative stress.," Small, vol. 8, no. 21, pp. 3326-3337, 2012. DOI:
10.1002/smll.201200772

[83] G. A. Sotiriou and S. E. Pratsinis, "Antibacterial activity of nanosilver ions and

particles," Environmental Science & Technology, vol. 44, no. 14, pp. 5649-5654, 2010. DOI:
10.1021/es101072s

[84] Z. M. Xiu, Q. B. Zhang, H. L. Puppala, V. L. Colvin and P. J. Alvarez, "Negligible

particle-specific antibacterial activity of silver nanoparticles.," Nano letters, vol. 12, no. 8,
pp. 4271-4275, 2012. DOI: 10.1021/nl301934w

[85] J. Highsmith, "Nanoparticles in biotechnology, drug development and drug delivery.

Report No. BIO113A," BCC Research: Market Forecasting, 2012, 2014.

[86] V. Sastri, “Plastic in Medical Devices: Properties, Requirements and Applications”,

1st Ed., Burlington, MA, USA,: Elsevier, 2010.

[87] K. Maldonado-Lara, G. Luna-Bárcenas, E. Luna-Hernández, F. Padilla-Vaca, E.

Hernández-Sánchez, R. Betancourt-Galindo, J. Menchaca-Arredondo and B. L. España-
Sánchez, "Preparación y Caracterización de Nanocompositos Quitosano-Cobre con
Actividad Antibacteriana para aplicaciones en Ingeniería de Tejidos," Revista mexicana de
ingeniería biomédica, vol. 38, no. 1, pp. 306-313, 2017. DOI: 10.17488/RMIB.38.1.26
[88] A. Lazary, I. Weinberg, J. J. Vatine, A. Jefidoff, R. Bardenstein, G. Borkow and N.
Ohana, "Reduction of healthcare-associated infections in a long-term care brain injury
ward by replacing regular linens with biocidal copper oxide impregnated linens,"
International journal of infectious diseases, vol. 24, pp. 23-29, 2014. DOI:
10.1016/j.ijid.2014.01.022