Protective hybrid coating containing silver, copper and zinc cations effective against human immunodeficiency virus and other enveloped viruses

Hodek et al. BMC Microbiology (2016) 16:56 DOI 10.1186/s12866-016-0675-x RESEARCH ARTICLE Open Access Protective hybrid coating containing silver, copper and zinc cations effective against human immunodeficiency virus and other enveloped viruses Jan Hodek1, Veronika Zajícová2, Irena Lovětinská-Šlamborová2,3, Ivan Stibor2,4, Jana Müllerová2,4 and Jan Weber1* Abstract Background: Healthcare-acquired infections by pathogenic microorganisms including viruses represent significant health concern worldwide. Next to direct transmission from person-to-person also indirect transmission from contaminated surfaces is well documented and important route of infections. Here, we tested antiviral properties of hybrid coating containing silver, copper and zinc cations that was previously shown to be effective against pathogenic bacteria including methicillin-resistant Staphylococcus aureus. Hybrid coatings containing silver, copper and zinc cations were prepared through radical polymerization via sol-gel method and applied on glass slides or into the wells of polymethylmethacrylate plates. A 10 μl droplet of several viruses such as human immunodeficiency virus type 1 (HIV-1), influenza, dengue virus, herpes simplex virus, and coxsackievirus was added to coated and uncoated slides or plates, incubated usually from 5 to 240 min and followed by titer determination of recovered virus. Results: Scanning electron microscopy analysis showed better adhesion of coatings on glass surfaces, which resulted in 99.5–100 % HIV-1 titer reduction (3.1 ± 0.8 log10TCID50, n = 3) already after 20 min of exposure to coatings, than on coated polymethylmethacrylate plates with 75–100 % (1.7 ± 1.1 log10TCID50, n = 3) and 98–100 % (2.3 ± 0.5 log10TCID50, n = 3) HIV-1 titer reduction after 20 and 120 min of exposure, respectively. Slower virucidal kinetics was observed with other enveloped viruses, where 240 min exposure to coated slides lead to 97 % (dengue), 100 % (herpes simplex) and 77 % (influenza) reduction in virus titers. Interestingly, only marginal reduction in viral titer after 240 min of exposure was noticed for non-enveloped coxsackie B3 virus. Conclusions: Our hybrid coatings showed virucidal activity against HIV and other enveloped viruses thus providing further findings towards development of broad-spectrum antimicrobial coating suitable for surfaces in healthcare settings. Keywords: Hybrid coating, Virucidal effect, HIV, Enveloped viruses Background Healthcare–associated infections (HAIs) by pathogenic bacteria, viruses and other microorganisms constitute significant cause of morbidity and mortality worldwide. Although exact statistical data are lacking, 1.7 million HAIs were estimated to occur in 2002 in U.S. hospitals alone [1]. More recent survey indicates that everyday approximately 1 of every 25 patients in U.S. acute care * Correspondence: 1 Institute of Organic Chemistry and Biochemistry AS CR, Flemingovo nam. 2, 166 10 Prague 6, Czech Republic Full list of author information is available at the end of the article hospitals has at least one HAI [2]. Next to direct transmission from person-to-person indirect transmission from contaminated surfaces is also well documented and important route of infections. Self-decontaminating surfaces would represent additional safety measure towards preventing transmission in healthcare settings. In recent years a growing interest is seen in the use of organic-inorganic hybrid materials in medicine, for example antibacterial protective coatings applied on number of devices used in healthcare [3–7], micro and/or nano needles for transdermal drug delivery [8], antibacterial protective coatings on the surface of artificial joints [9], or dental implants [10]. © 2016 Hodek et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Hodek et al. BMC Microbiology (2016) 16:56 Hybrid materials are very conveniently prepared by sol-gel method, which can be briefly described as a special process of glass and ceramics manufacture at room or slightly elevated temperature. This technique became an independent and a very comprehensive discipline, documented by numerous books [11–15] and reviews [16, 17]. With the introduction of organically-modified silicates (ORMOSILs) the sol-gel products started to be an interesting precursor for number of hybrid materials applicable in medicine. Specifically 3-(trimethoxysilyl)propyl methacrylate (TMSPM) either in the pure form or in addition to tetrafunctional silica precursors such as tetraethylorthosilicate (TEOS) or tetramethylorthosilicate (TMOS) allows large variations in optical, mechanical and chemical properties and can be tailored for specific uses [18, 19]. In addition, the sol-gel process allows the encapsulation of different nanoparticles with known antimicrobial activity e.g. metallic nanoparticles such as Ag, Cu, Zn, Au etc. [4, 20]. From metal nanomaterials with biocidal properties, silver and copper received the most attention. Next to well documented bactericidal activities both silver and copper showed potent virucidal properties [21]. Several studies have confirmed anti-HIV activity of silver nanoparticles [22–24] inhibiting most likely entry step by binding directly with gp120 [25]. Furthermore, silver nanoparticles were shown to inhibit herpes simplex virus type 1 [26] and 2 [27], vaccinia virus [28], respiratory syncytial virus [29], influenza A [30], tacaribe virus [31] and hepatitis B virus [32]. Virucidal activity of copper in the form of copper oxide was evaluated in variety of materials such as fibers, latex, filter matrices and other polymeric materials [33, 34]. Copper oxide-containing filters effectively neutralized HIV-1 in medium and breastmilk and reduced cell-associated HIV in dose-dependent manner [35, 36]. In addition, these filters reduced infectious viral titers of several DNA and RNA viruses, among others yellow fever virus, influenza A virus, measles virus, respiratory syncytial virus, adenovirus type 1 and cytomegalovirus [37]. Recently, it was shown that cuprous compounds deactivate more efficiently bacteriophages and bacteria than cupric compounds [38]. Photoactivation of titanium dioxide by UV generates reactive oxygen molecules on the surface of TiO2 and has been shown to effectively inactivate influenza A virus [39], HIV-1 [40], and murine norovirus [40, 41]. Halogen and interhalogen TiO2 nanoparticles, except for chlorinated adduct, completely in (...truncated)