**4. Metals**

Metals such as copper, silver, and gold have been recognized since ancient times as having some health benefits, and the antibacterial properties of metals have since been well-studied [29]. In contrast, the mechanisms of metal inactivation of specific viruses remain unclear, although a number have been proposed and evaluated. Certain metals in trace amounts are critical to the function of viral proteins and genetic processes; however, levels in excess cause structural damage and affect viability [14]. The presence of these metals stimulates the generation of reactive oxygen species and damages viral envelopes as well as nucleocapsid proteins [30]. Metals can be incorporated into plastics and fabrics, used as actives in coating formulations, and fashioned directly into surfaces for direct use (e.g., copper sheets for incorporation into high-touch surfaces).

### **4.1 Copper**

The antimicrobial properties of copper have been extensively studied, with efficacy demonstrated over a broad range of temperature and humidity values [1]. The proposed antiviral mechanisms of solid-state copper, copper oxides, and copper alloys against enveloped and non-enveloped viruses have been thoroughly reviewed [31]. Copper (I), (II), (III) ions act directly by denaturing viral surface proteins, and indirectly by the formation of reactive oxygen species that damage viral RNA and DNA. Copper surfaces inactivated infectious influenza A (H1N1) within 6 hours by 3 to 4 log10, relative to virus levels remaining on stainless steel coupons [32]. Although copper has demonstrated broad-spectrum antimicrobial activity, it may be impractical to replace bulk materials within high-traffic areas (e.g., clinical settings) with copper products or components. The recent development of cold- and thermally-applied copper sprays, as well as fixed copper nanoparticle coatings and paints, enables continuously active disinfection measures against a spectrum of viruses [16]. Copper nanoparticles in the oxide form have shown promise against herpes simplex virus, human norovirus, and influenza A (H1N1) [31]. When applied using the cold spray technique, copper nanoparticles reduced infectious influenza A virus particles to levels below detection within 10 minutes [33].
