Mechanism of Antimycotic Activity of Nanomaterials

Enormous literature on antifungal potential of nanoscale silver [52–54,59,83,84], copper/copper oxide [59,62], and zinc/zinc oxide [40] materials exists (Figure 3). The fundamental benefit of the nanoparticulate fungicide is the performance of these formulations equivalent or superior to the respective bulk salt formulations at relatively lower application doses thereby effectively addressing the phyto- and ecotoxicity issues posed due to the release of the metal cations [85]. There exist multiplexed nanomaterial–fungal cell interactions. The nanomaterial internalization in the fungal cell occurs through three possible mechanisms; (i) nonspecific but direct internalization of the small-sized, mostly, spherical nanoparticles, (ii) specific receptor-mediated adsorption followed by internalization of the NPs, or (iii) internalization of dissolved metal/nonmetal ions through membrane-spanning ion transport proteins (Figure 3). Nanomaterials particularly the metal/metal oxide and nonmetal oxide nanoparticles can curb fungal growth through mechanisms that can be dichotomized as (a) antimycotic effect due to generation of ROS and dissolution of the nanoparticles in the cell environment to release specific ions leading to metal/nonmetal ion toxicity and (b) regulation of the mycotoxin-producing genes for decreased or no expression. A detailed illustration of the same for zinc nanomaterials will be incorporated in Section 3.

**Figure 3.** Effect of application of different types of nanoparticles on cellular components and organelles in a fungal cell.

#### Mechanism of Antiviral Activity of Nanomaterials

– – The M/MO/NM/NMO nanomaterials possess antiviral activity against microbial [86], animal [87–90], and human viruses [91–97] as depicted in several published reports. The green synthesized (microbial/plant cell extract-derived) nanoparticles particularly silver [98] and gold nanoparticles [99] or their composites [98] have been documented to exhibit virus-neutralizing or -inhibiting properties. Likewise, the role of zinc nanomaterials for the virostatic effect [100], virus neutralization, and for immune-modulatory significance against the emerging COVID-19 causative agent [101] has been well identified.

−1 −1 The application of nanomaterials for the control and treatment of viral disorders in crop plants has also been evaluated and established through molecular biology and in planta assays [45]. One-week preapplication of silver NPs at low concentration (50 ppm) on tomato plants decreased the disease severity and induced systemic resistance against two common tomato viruses, namely, Tomato mosaic virus, and Potato virus Y [102]. However, another in planta study showed significant inhibition of Tomato spotted wilt virus on foliar spray of AgNPs (200 ppm) 1 day after artificial inoculation of the TSWV, whereas the lowest and substantially low inhibition was recorded when AgNPs were applied along with and before the virus inoculation, respectively [103]. Similar results have been documented by Elbeshehy et al. [104] on foliar spray treatment of biogenically synthesized AgNPs derived from cell-free extracts of three *Bacillus* bacteria species (*B. pumilus, B. persicus*, and *B. licheniformis*). Complete inhibition of typical disease symptoms was recorded when the AgNPs were applied (concentration: 0.1 µg µL −1 ) 24 h postinoculation with bean yellow mosaic virus in fava bean cv. Giza 3 variety, whereas weak symptoms were recorded when AgNPs formulation was sprayed on foliage simultaneously to that of swab inoculation of the fava bean plants. Low concentration of fungus generated AgNPs formulation (derived from *Curvularia lunata* cell extracts, concentration: 100 ppm) on spray treatment on the foliage of approximately 1 month (35 days) old tobacco plants (*Nicotiana tabacum* cv. *Xanthi* nc) followed by mechanical inoculation of two leaves (5th and 6th true leaf) with PVY-Ros1 virus after 2 days resulted in 2.67-fold decrease in the appearance of characteristic red lesions/infection loci in AgNP-treated plants. Development of nano-Ag composites can further improve the antiviral activity, for instance, graphene oxide-AgNP composite treatment (at 1 µg mL −1 ) reduced the visible symptoms of disease caused by Tomato bushy stunt virus in test lettuce plants [105].

Apart from silver NPs, daily foliar spraying treatment for approximately 2 weeks (12 days) of micronutrient iron oxide NPs (Fe3O<sup>4</sup> NPs, size: 20 nm, concentration: 100 µg mL−<sup>1</sup> ) enhanced the resistance of tobacco plants against Tobacco mosaic virus [106]. Another report involved daily foliar spray treatment on *Nicotiana benthamiana* plants with Fe2O<sup>3</sup> (concentration: 50 mg L−<sup>1</sup> ) or TiO<sup>2</sup> NPs (concentration: 200 mg L−<sup>1</sup> ) (amount: 5 mL) for 21 days. When these plants were challenged with Turnip mosaic virus (green fluorescent protein-tagged TuMV), the plants exhibited significant inhibition in the proliferation of the inoculated TuMV, particularly decrease in coat protein content as identified through a decrease in the fluorescent intensity of GFP marker in new emerging leaves [107].
