PMC:7299399 / 55941-60310 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7299399","sourcedb":"PMC","sourceid":"7299399","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7299399","text":"Silver, copper, and zinc show intrinsic antimicrobial properties and are already used in medical equipment and in healthcare settings. For instance, Ag is used in wound dressing and in urinary and intravascular catheters. It is advantageous to use NPs composed of these metals rather than bulk materials or the metal ions themselves because NPs release the toxic metal ions slowly and progressively right where the antimicrobial action is needed and because NPs can accumulate within cells without being expelled by specialized efflux pumps. The antimicrobial property of Ag has been used since ancient times for medical applications154 and more recently in commercial products such as silver zeolites in paints155 and in food trays156 as biocide. The antiviral efficiency of Ag NPs has been demonstrated in a variety of viruses, including HIV-1,157 monkeypox virus,158 bacteriophages UZ1 and MS2,159,160 murine norovirus MNV1,159,160 HSV,161 HBV,162 and, recently, in porcine epidemic diarrhea virus (PEDV).163Antiviral properties of Ag NPs arise from three different mechanisms. First, Ag(0) NPs dissolve and release some toxic Ag(I) forms (including Ag+ ions), which could be responsible for their antiviral activity. As a soft metal, Ag shows strong affinity toward sulfur, and therefore, it interacts strongly with thiols from small molecules such as cysteine or glutathione or with sulfhydryl groups in the active sites of many enzymes. Ag(I) may interact with surface proteins of viruses or accumulate in host cells and further interact with thiol-containing enzymes that are involved in virus replication, thus hampering their functions. This hypothesis was proposed by Zodrow et al. to explain the antiviral property of Ag NPs for bacteriophage MS2 and by De Gusseme et al. in response to MNV-1 exposed to Ag NPs.159,164 Moreover, Ag2S nanoclusters (NCs) with diameters of 2.5 and 4 nm showed effective inhibition of PEDV replication in Vero cells via inhibition of the synthesis of viral negative-strand RNA and of virus budding from the cells, but not by preventing their anchorage on cell membranes or their intracellular penetration. Exposing cells to Ag+ ions at the same concentration did not inhibit virus replication, which led the authors to conclude that the antiviral property of Ag NCs was independent of the release of Ag(I).163 However, the mechanisms by which Ag+ ions and Ag NCs enter into cells are different and, consequently, their local distribution and handling within cells would also be different. This difference could lead to different modes of toxic action for Ag ions and Ag NCs toward the viruses that have infected cells. For instance, Ag NCs may aggregate in intracellular areas where vital steps of the viral cycle are performed, such as protein or genome production or assembly of nucleocapsids before their release into the extracellular space, whereas Ag(I) could aggregate in other areas of the cells or be rapidly eliminated. Second, the antiviral efficiency of Ag NPs would derive from physical interaction of Ag NPs with the surface of viruses, which would impede their docking on host cells and limit their infectivity. This mechanism was demonstrated by Elechiguerra et al. for HIV-1 exposed to 1–10 nm Ag NPs157 and by Orlowski et al. for HSV-2 exposed to 13, 33, and 46 nm Ag NPs coated with tannic acid.161 Elechiguerra et al. found that the optimal size of Ag NPs was around 10 nm, with larger or smaller NP sizes showing weaker physical interaction with the virus. In contrast, Orlowski et al. found that the larger the NP, the more effective its blocking was of virus attachment to host cell. The same mechanism, combined with the release of Ag(I), was also proposed by De Gusseme et al. to explain the reduced infectivity of MNV-1 virus when exposed to 11.2 nm biogenic Ag NPs.159 Finally, this docking of Ag NPs on the surface of viruses could be associated with the local release of ROS from the Ag NP surface, which would damage the envelope and/or membrane of the virus. Ag NPs are already used in wound dressings, catheters and other medical equipment; their use could also be envisaged to confer biocidal properties to paints used in healthcare settings, or to air filters or face masks. Ag NPs loaded on filters show effective antiviral activity against bacteriophage MS2, which drops with dust 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