SARS-CoV-2 (COVID-19), a novel coronavirus causing life-threatening pneumonia, caused a pandemic starting in 2019 and caused unprecedented economic and health crises all over the globe. This requires the rapid discovery of anti-SARS-CoV-2 drug candidates to overcome this life-threatening pandemic. Strawberry (Fragaria ananassa Duch.) and ginger (Zingiber officinale) methanolic extracts were used for silver nanoparticle (AgNPs) synthesis to explore their SARS-CoV-2 inhibitory potential. Moreover, an in silico study was performed to explore the possible chemical compounds that might be responsible for the anti-SARS-CoV-2 potential. The characterization of the green synthesized AgNPs was carried out with transmission electron microscope (TEM), Fourier-transform infrared, spectroscopy ultraviolet-visible spectroscopy, zeta potential, and a dynamic light-scattering technique. The metabolic profiling of strawberry and ginger methanolic extract was assessed using liquid chromatography coupled with high-resolution mass spectrometry. The antiviral potential against SARS-CoV-2 was evaluated using an MTT assay. Moreover, in silico modeling and the molecular dynamic study were conducted via AutoDock Vina to demonstrate the potential of the dereplicated compounds to bind to some of the SARS-CoV-2 proteins. The TEM analysis of strawberry and ginger AgNPs showed spherical nanoparticles with mean sizes of 5.89 nm and 5.77 nm for strawberry and ginger, respectively. The UV-Visible spectrophotometric analysis showed an absorption peak at λmax of 400 nm for strawberry AgNPs and 405 nm for ginger AgNPs. The Zeta potential values of the AgNPs of the methanolic extract of strawberry was −39.4 mV, while for AgNPs of ginger methanolic extract it was −42.6 mV, which indicates a high stability of the biosynthesized nanoparticles. The strawberry methanolic extract and the green synthesized AgNPs of ginger showed the highest antiviral activity against SARS-CoV-2. Dereplication of the secondary metabolites from the crude methanolic extracts of strawberry and ginger resulted in the annotation of different classes of compounds including phenolic, flavonoids, fatty acids, sesquiterpenes, triterpenes, sterols, and others. The docking study was able to predict the different patterns of interaction between the different compounds of strawberry and ginger with seven SARS-CoV-2 protein targets including five viral proteins (Mpro, ADP ribose phosphatase, NSP14, NSP16, PLpro) and two humans (AAK1, Cathepsin L). The molecular docking and dynamics simulation study showed that neohesperidin demonstrated the potential to bind to both human AAK1 protein and SARS-CoV-2 NSP16 protein, which makes this compound of special interest as a potential dual inhibitor. Overall, the present study provides promise for Anti-SARS-CoV-2 green synthesized AgNPs, which could be developed in the future into a new anti-SARS-CoV-2 drug.

Microbial resistance, oxidative stress, and inflammatory conditions are among the leading causes of death worldwide. In the current work, silver nanoparticles (AgNPs) were biosynthesized using the aqueous extracts of parsley, corn silk (CS), gum Arabic (GA) or combination of the three extracts. The formed nanoparticles were characterized using three techniques including transmission electron microscopy (TEM), UV-visible spectrophotometer and Fourier-transform infrared spectroscopy (FTIR). The antioxidant, anti-inflammatory, and antimicrobial activities were tested for the formed nanoparticles, the aqueous extracts of each of the three plants and their combination. Oxidative stress was induced by alloxan which promoted the development of diabetes mellitus in rats. Inflammation was induced by injecting carrageenan in rats' paws. Pathogenic microorganisms causing serious urinary tract infection (UTI) were selected for the antimicrobial assay. All aqueous extracts and the biosynthesized AgNPs showed variable degrees of antioxidant, anti-inflammatory and antimicrobial activities, however, the AgNPs biosynthesized by the combination of the three aqueous extracts was the most effective one. LC/MS was done to identify the compounds present in the crude extracts that may be responsible for the observed biological activities. LC/MS resulted in the identification of 13 compounds. Docking experiments on COX-1 (cyclooxygenase-1) and COX-2 (cyclooxygenase-2) were performed to determine the compounds responsible for the antiinflammatory activity of the extracts. The results showed that silver nanoparticles synthesized by the combination of the three aqueous extracts are considered promising candidates for the development of antioxidant, anti-inflammatory and antimicrobial agents. photochemical [10], electrochemical [7, 11], reverse micelle [12], thermal decomposition [13], radiation [7,14] and microwave-assisted [7] methods. Most of these methods require the use of hazardous chemicals and high energy for the preparation of nanoparticles. Biological synthesis of nanoparticles involves the use of natural materials such as plants, bacteria, fungi [1,5,15]. The use of plants for the synthesis of nanoparticles have an advantage over other biological methods as it does not involve the use of cell culture, and does not need longer incubation time required for the reduction of metal ions [16,17]. Plants are known to contain various secondary metabolites such as alkaloids, terpenoids, flavonoids and tannins which provide suitable reducing and surface agents for the nanoparticle synthesis and stabilization. Biopolymers such as cellulose, chitosan, alginate, dextran and tree gums are another family of natural sources which were used for the reduction and stabilization of nanoparticles [17,18].Recently, pathogenic bacteria and fungi such as Staphylococci spp., Enterococci spp., Klebsiella pneumoniae, and Pseudomonas spp. demonstrated resistance to commercially available antimicrobial agents at an increasing rate and has become a global thr...

Gum Arabic (GA), parsley, and corn silk have been traditionally used for renal failure patients worldwide. This study aimed at probing the mechanism of the combined extracts, namely, GA (3 g/kg/day), parsley (1 g/kg/day), and corn silk (200 mg/kg/day), as nephroprotective agents in mice after amikacin (1.2 g/kg) single dose through exploration of their action on G-protein coupled receptors (GPR) 41 and 43 and the ensuing lysosomal biogenesis. Western blotting was employed for renal levels of bcl-2-associated X protein (BAX) and cytosolic cathepsin D; cell death markers, nuclear transcription factor EB (TFEB), and lysosomal associated membrane protein-1 (LAMP-1); and lysosomal biogenesis indicators. Liquid chromatography–mass spectrometry (LC-MS) and docking were also employed. After amikacin treatment, BAX and cathepsin D levels were upregulated while LAMP-1 and nuclear TFEB levels were inhibited. The combined extracts inhibited BAX and cytosolic cathepsin D but upregulated LAMP-1 and nuclear TFEB levels. Docking confirmed GPR modulatory signaling. The combined extracts showed GPR signal modulatory properties that triggered lysosome synthesis and contributed to reversing the adverse effects of amikacin on renal tissues.