Strawberry and Ginger Silver Nanoparticles as Potential Inhibitors for SARS-CoV-2 Assisted by In Silico Modeling and Metabolic Profiling

Abstract

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.

Nanotechnology Applications of Flavonoids for Viral Diseases

“…Green silver NPs prepared with silver nitrate and methanolic extracts of strawberry (Fragaria ananassa Duch.) or ginger (Zingiber officinale Roscoe) have been reported for their strong anti-viral activity against SARS-CoV-2, a finding in agreement with binding of the common phytochemical neohesperidin with both human AAK1 (AP2 associated kinase 1) protein and SARS-CoV-2 NSP16 protein [316]. Green silver NPs prepared with silver nitrate and Curcuma longa L. (Zingiberaceae) tuber powder extracts have been mentioned as being of potential use for biomedical purposes [317]; notably, curcumin, a polyphenolic phytochemical ((1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), also called diferuloylmethane) found in Curcuma longa tubers, is regarded as a potential treatment for COVID-19 [318].…”

Antiviral Properties of Silver Nanoparticles against SARS-CoV-2: Effects of Surface Coating and Particle Size

“…Jeremiah et al evaluated AgNPs with different sizes and concentrations and found that 1–10 ppm of the particles with a diameter of approximately 10 nm could effectively neutralize extracellular SARS-CoV-2, and cytotoxicity was observed at >20 ppm [ 19 ]. Al-Sanea et al applied strawberry and ginger extracts in the fabrication of AgNPs, to enable the anti-SARS-CoV-2 activity [ 38 ]. Surface modification of AgNPs can significantly affect their biocompatibility and their interaction with cells [ 39 ].…”

Ginger from Farmyard to Town: Nutritional and Pharmacological Applications

“…To further evaluate the antiviral activity, in silico molecular docking study was conducted to examine the potential phytochemicals that might bind to and inhibit SARS-CoV-2 proteins. Among 30 compounds, neohesperidin showed better binding affinity to SARS-CoV-2 NSP16 protein (Al-Sanea et al, 2021).…”