key: cord-0809227-ua7bo6e9
authors: Cortes, Aaron A.; Zuñiga, Jorge M.
title: The use of copper to help prevent transmission of SARS-Coronavirus and Influenza viruses. A general Review
date: 2020-08-15
journal: Diagn Microbiol Infect Dis
DOI: 10.1016/j.diagmicrobio.2020.115176
sha: 671fd16fc56c999551efb3efa3eef41ca1ad7e7f
doc_id: 809227
cord_uid: ua7bo6e9

OBJECTIVES: The SARS-CoV-2 is the causative agent of the COVID-19 disease a Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV). Its main transmission pathway is through large respiratory droplets, as well as direct and indirect contact. Copper in different format has been used in research and clinical settings to reduce the risk of bacterial and viral contamination. Therefore, this review aims to search for evidence about the biocidal properties of copper over coronaviridae family. METHODS: A literature review using PubMed and Ovid servers without date or language restrictions. The search was carried out on March 7(th), 2020 using the following search terms [Copper] Coronavirus OR CoV OR SARS OR MERS OR Influenza. RESULTS: Copper destroys the replication and propagation abilities of SARS-CoV, influenza and other respiratory viruses, having high potential disinfection in hospitals, communities, and households. Copper can eliminate pathogenic organisms such as coronavirus bacterial strains, influenza virus, HIV, and fungi after a short period of exposure. CONCLUSIONS: Copper seems to be an effective and low-cost complementary strategy to help to reduce the transmission of several infectious diseases by limiting nosocomial infectious transmission. Copper oxide or nano-compounds may be used as filters, face masks, clothing and hospital common surfaces to reduce viruses and bacterial incubation.

The SARS-CoV-2 is the causative agent of the COVID-19 disease. A coronaviridae enveloped positive-sense single-stranded RNA virus. Its main transmission pathway is through large respiratory droplets and direct and indirect contact. Phylogenetic analyses indicate a close relation to bat SARS-like and MERS-like coronavirus (Tang et al. 2020a ). The first 9 cases of SARS-CoV-2 were analysed, sequences of the virus were more than 99.98% similar between them. SARS-CoV-2 share at least 88% of genetic sequence similarities with SARS-Like Coronaviruses and share 79% similar sequence identity with SARS-CoV and MERS-COV about 50%, additionally, SARS-CoV-2 have similar receptor binding domain structure compared with SARS-CoV (Lu et al. 2020; Wang et al. 2020c ). Therefore, despite survival time and conditions affecting SARS-CoV-2 remains unknown, it is plausible to extrapolate knowledge from SARS-CoV family; it is a zoonotic bat originated virus; from the family of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) (Song et al. 2019) ; and capable of survive several days in the environment (Otter et al. 2016 ; European Centre for Disease Prevention and Control 2020).

The emergence of this novel coronavirus (SARS-CoV-2) on December 2019 in Wuhan, Hubei province of China, is having a significant impact over the world, counting and summing cases in every continent in only a few months (Tang et al. 2020a; Wang et al. 2020a ). According to the World Health Organization (WHO) situation report 179(World Health Organisation), up to 17 th July 2020 the pandemic have killed 585,727 people with cases reported in 216 countries. Due to its significant impact, the emergence of this novel coronavirus has been declared a global health emergency. The fast and worldwide spreading of the virus points at a human-to-human transmission.

J o u r n a l P r e -p r o o f Journal Pre-proof SARS-CoV gained attention after the 2003 pandemic (Drosten et al. 2003; Ksiazek et al. 2003 ) that killed 774 individuals in 24 countries and later in 2012 MERS-CoV killed 858 across 25 countries. Since then, some studies have described virus characteristics (Yip et al. 2007 ). Its influenza-like symptoms are non-specific and may include cough, breathing difficulties, runny nose, fever and headache. Laboratory exam shows lymphopenia and bilateral ground-glass opacity or consolidation CT scans, making difficult differential diagnostic against influenza or other respiratory viruses (Wang et al. 2020a) . Unlike influenza, these symptoms seem to last longer in SARS-CoV-2 infection (Tang et al. 2020a) , becoming a life-threatening condition for specific risk groups, such as immune-compromised and older patients. Several treatments are currently under study, being the most promising the use of remdesivir and chloroquine . Other medications are also under study with fewer positive results, such as hydroxychloroquine (Gao et al. 2020; Tang et al. 2020b ) and azithromycin (Gautret et al. 2020) in combination with hydroxychloroquine.

Since the 2019-nCoV-2 outbreak, extraordinary public health measures have been implemented around the globe to help reduce virus spreading. These measures mainly point at people's transport restriction including quarantine of suspicious cases, airport and public transport closure, massive events cancellation, and social distancing and isolation. Preventing campaign has been launched by several world-leading agencies(Public Health England; World Health Organisation; CDC 2020) and from almost every governmental Health Department. Preventing actions, such as frequent hand-washing, correct mouth-covering when coughing and use of masks are common indications have given way to increasingly restrictive measures aiming to social distancing and isolation. (Borkow et al. 2010 (Borkow et al. , 2011 Fujimori et al. 2012; Imai et al. 2012; Majbauddin et al. 2015; Warnes et al. 2015; Ito et al. 2016; Minoshima et al. 2016; Zerbib et al. 2020) . Copper has been used in clinical settings to reduce the risk of bacterial and viral contamination, complementing traditional protocols. Furthermore, the addition of copper nanoparticles to polymer/plastic matrices can also produce highly effective antimicrobial materials. This review highlights the results of the research studying the effect of copper over the coronaviruses and influenza, summarising the state-of-the-art related its antiviral properties.

PubMed and Ovid servers were used without date or language restrictions. The PICOS method was followed to identify suitable terms. Table I Figure 1 describes the search phases. Most of the research about the use of copper or copper alloy is related to influenza virus.

Noyce (Noyce et al. 2007 ) studied the effect of copper over influenza virus: 20µl of virus (10 8 particles) were inoculated into copper or stainless steel; about 500,000 virus particle remained infectious after 24 hours incubation on stainless steel, on the other hand, after 6 hours on copper incubation only 500 particles remained viable. Similarly to Zerbib (Zerbib et al. 2020 ) study;

influenza may not be prevented by replacing steel fittings with copper; however, copper may reduce transmission. Miyamoto (Miyamoto et al. 1998 ) in a laboratory model, demonstrated that copper chelates inhibit apoptosis of the influenza virus, and such effect is independent of the influenza type. Additionally, copper chelates inhibited viruses release during apoptosis.

Minoshima (Minoshima et al. 2016 these properties can be applied to filters, masks and clothing by mixing or coating polymers base materials. Ito (Ito et al. 2016 ) in a laboratory model shown that sodium copper chlorophyllin had antiviral effect against influenza and HIV. Copper chlorophyllin inhibits the virus-to-cell interaction on the cell surface and this mechanism has been described for several microbes (Benati et al. 2009; Majbauddin et al. 2015) .

Few but conclusive studies have focused on the antiviral properties of copper against coronavirus. Han(Han et al. 2005 ) studied the effect of metal catalysts of Cu/Al203 against SARS-CoV, baculovirus and E. Coli. After 5 minutes of exposure, the infectivity dropped down to undetectable levels. SARS-CoV inactivation was achieved only when the loading viruses on the surfaces were exposed to air. Considering that central air conditioning systems are known pathways for infectious agents; the author concludes that the capacity to inactivate viruses or bacteria in the air filtered by AC systems depends on the efficient usage of oxygen, having the potential to disinfect the air in community settings and health services.

Human SARS and MERS coronavirus, as well as H1N1, H5N1 and H5N7 influenza viruses share an important number of characteristics. These viruses are RNA respiratory viruses from zoonotic origins that have mutated for human-to-human transmission by droplets of about 5µm of diameter. These droplets may directly contact the nose, mouth or eyes of the recipient. Indirect contact, involving contaminated surfaces (Bridges et al. 2003; Boone and Gerba 2007) is also a predominant transmission route (Brankston et al. 2007; Spicknall et al. 2010) . These respiratory viruses are the main cause of deaths among any other infectious agent (Warnes et al. 2015) .

One of the causes of the high rate of transmission of respiratory viruses relates with it capability to survive on dry surfaces for more than five days on a variety of daily use surfaces, such as ceramic tiles, glass, rubber and stainless steel (Warnes et al. 2015) . Nevertheless, it has also been reported that, depending on the surface, the SARS coronavirus, MERS coronavirus and HCoV can remain infectious for up to 9 days, and for up to 28 days at 4°C (Kampf et al. 2020) . Thus, the virus can survive for a considerably long time until a person touches a surface contaminated by respiratory droplets from an infected individual. In 2015 the study by Warnes (Warnes et al. 2015) showed conclusive results related to the effect of copper on HCoV 229E. HCoV 229E remain infectious for at least 5 days on nonmetal surfaces such as Teflon, PVC, ceramic tiles, glass, silicone rubber and stainless steel. On the other hand, when exposed to copper (metal surface) and copper alloy (Cu/Zn brasses) after 10 minutes of exposition viral genomes and morphology were irreversibly affected. Warnes described rapid damage to the surface proteins and membrane, breaking the envelope or losing its capacity of self-containing folding upon itself. Coronavirus genomic RNA after copper exposure revealed nonspecific fragmentation, and this pattern of damage increased as exposure time increased.

Some application designs of this knowledge have been successfully tested; Borkow (Borkow et al. 2010 ) developed a face mask impregnated with copper oxide and tested its antiviral effects against influenza (H1N1 and H9N2 Based on the reviewed literature; copper nanoparticles together with efficient usage of oxygen appears to be the most effective formulation against Coronaviruses.

The described data appears to support the use of copper in different presentations to actively inactivate viruses (and a wide range of microorganisms) and seems to be an effective and low-cost complementary strategy to help reducing transmission of several infectious diseases such as the coronavirus. Nevertheless, and despite the genetic similarities, more research would be beneficial to support its usage with the new SARS-Cov-2.

However, the described data support the incorporation of copper alloys or impregned copper materials on health services as a complementary strategy that may help reduce bacterial and viral load, therefore; limiting nosocomial infections and reducing transmission from touching surfaces in the communal city or home areas (Prado J et al. 2012; Warnes et al. 2015) .

Additionally, copper oxide or nano-compounds may be used as filters, face masks, clothing and hospital common use devices to reduce viruses and bacterial incubation (Fujimori et al. 2012 ).

Some copper product application has been tested with conclusive results, describing copper potent antiviral properties, reducing disease spreading by limiting environmental contamination and subsequent infections (Borkow et al. 2010 ).

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