RNA-dependent RNA-polymerase (RdRp) and 3C-like proteinase (3CL pro ) are two main enzymes that play a key role in the replication of SARS-CoV-2. Zinc (Zn) has strong immunogenic properties and is known to bind to a number of proteins, modulating their activities. Zn also has a history of use in viral infection control. Thus, the present study models potential Zn binding to RdRp and the 3CL pro . Through molecular modeling, the Zn binding sites in the aforementioned two important enzymes of viral replication were found to be conserved between severe acute respiratory syndrome (SARS)-coronavirus (CoV) and SARS-CoV-2. The location of these sites may influence the enzymatic activity of 3CL pro and RdRp in coronavirus disease 2019 (COVID-19). Since Zn has established immune health benefits, is readily available, non-expensive and a safe food supplement, with the comparisons presented here between SARS-CoV and COVID-19, the present study proposes that Zn could help ameliorate the disease process of COVID-19 infection.

Wounds continue to be a serious medical concern due to their increasing incidence from injuries, surgery, burns and chronic diseases such as diabetes. Delays in the healing process are influenced by infectious microbes, especially when they are in the biofilm form, which leads to a persistent infection. Biofilms are well known for their increased antibiotic resistance. Therefore, the development of novel wound dressing drug formulations and materials with combined antibacterial, antibiofilm and wound healing properties are required. Nanomaterials (NM) have unique properties due to their size and very large surface area that leads to a wide range of applications. Several NMs have antimicrobial activity combined with wound regeneration features thus give them promising applicability to a variety of wound types. The idea of NM-based antibiotics has been around for a decade at least and there are many recent reviews of the use of nanomaterials as antimicrobials. However, far less attention has been given to exploring if these NMs actually improve wound healing outcomes. In this review, we present an overview of different types of nanomaterials explored specifically for wound healing properties combined with infection control.

Metal-based antimicrobials have been used for thousands of years to treat and prevent bacterial infections. Currently, both silver and copper are used in health care and industry to prevent and treat the spread of harmful bacteria. However, like most antimicrobial agents, their efficacy against polymicrobial infections has not been fully elucidated. Coinfection with Pseudomonas aeruginosa and Staphylococcus aureus and the resulting interactions have been implicated in higher virulence, antibiotic resistance, and increased chronic infections. Here, the influence of secreted compounds from P. aeruginosa on metal antimicrobial tolerance in S. aureus was examined. This study determined that multiple compounds from P. aeruginosa increase the tolerance of S. aureus to copper and/or silver when cultured in simulated wound fluid. The presence of these secreted compounds from P. aeruginosa during exposure of S. aureus to copper or silver increased the MIC from 500 μM to 2,000 μM for copper and 16 to 63 μM for silver. The contribution of specific compounds to S. aureus tolerance was determined using gene deletion and disruption mutants, and metabolite analysis. Compounds identified as potential contributors were then individually added to S. aureus during metal exposure. Copper tolerance in S. aureus was found to be increased by amino acids and dihydroaeruginoate (Dha) secreted by P. aeruginosa. The silver tolerance provided to S. aureus was influenced only by two amino acids, serine and threonine, as well as the Pseudomonas quinolone signal (PQS) molecules from P. aeruginosa. IMPORTANCE Alternative antimicrobials, such as metals, are one of the methods currently used to help mitigate antibiotic resistance. Metal-based antimicrobials such as copper and silver are used currently both to prevent and to treat infections. Although the efficacy of these antimicrobials has been determined in single-species culture, bacteria rarely exist in a single-species group in the environment. Both Pseudomonas aeruginosa and Staphylococcus aureus are often found associated with each other in severe chronic infections displaying increased virulence and antibiotic tolerance. In this study, we determined that multiple compounds secreted by P. aeruginosa are able to increase the tolerance of S. aureus to both copper and silver. This work demonstrates the expansive chemical communication occurring in polymicrobial infections between bacteria.

This chapter describes the antimicrobial uses of metals and metal-based compounds. It follows the historical use of metal-based antimicrobials (MBAs), their decline with the emergence of antibiotics and subsequent rediscovery with the advent of antibiotic resistance. Here, the potential mechanisms of metal toxicity are discussed, including binding biochemistries, production of reactive oxygen/nitrogen species, inhibition of protein/enzyme activity, interaction with the lipid cell membrane and effects on nutrient uptake and DNA damage. The potential of MBA nanoparticles, their use and the mechanisms of toxicity are briefly discussed. Current applications and formulations of a wide range of MBAs are examined and the consequences associated with their use provides the reader with recognition of our responsibility to prevent misuse.

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