Antiviral Activity of Zinc Oxide Nanoparticles against SARS-CoV-2.

The highly contagious SARS-CoV-2 virus is primarily transmitted through respiratory droplets, aerosols, and contaminated surfaces. In addition to antiviral drugs, the decontamination of surfaces and personal protective equipment (PPE) is crucial to mitigate the spread of infection. Conventional approaches, including ultraviolet radiation, vaporized hydrogen peroxide, heat and liquid chemicals, can damage materials or lack comprehensive, effective disinfection. Consequently, alternative material-compatible and sustainable methods, such as nanomaterial coatings, are needed. Therefore, the antiviral activity of two novel zinc-oxide nanoparticles (ZnO-NP) against SARS-CoV-2 was investigated in vitro. Each nanoparticle was produced by applying highly efficient "green" synthesis techniques, which are free of fossil derivatives and use nitrate, chlorate and sulfonate salts as starting materials and whey as chelating agents. The two "green" nanomaterials differ in size distribution, with ZnO-NP-45 consisting of particles ranging from 30 nm to 60 nm and ZnO-NP-76 from 60 nm to 92 nm. Human lung epithelial cells (Calu-3) were infected with SARS-CoV-2, pre-treated in suspensions with increasing ZnO-NP concentrations up to 20 mg/mL. Both "green" materials were compared to commercially available ZnO-NP as a reference. While all three materials were active against both virus variants at concentrations of 10-20 mg/mL, ZnO-NP-45 was found to be more active than ZnO-NP-76 and the reference material, resulting in the inactivation of the Delta and Omicron SARS-CoV-2 variants by a factor of more than 106. This effect could be due to its greater total reactive surface, as evidenced by transmission electron microscopy and dynamic light scattering. Higher variations in virus inactivation were found for the latter two nanomaterials, ZnO-NP-76 and ZnO-NP-ref, which putatively may be due to secondary infections upon incomplete inactivation inside infected cells caused by insufficient NP loading of the virions. Taken together, inactivation with 20 mg/mL ZnO-NP-45 seems to have the greatest effect on both SARS-CoV-2 variants tested. Prospective ZnO-NP applications include an antiviral coating of filters or PPE to enhance user protection.

Green Synthesized Zinc Oxide Nanoparticles Based on Cestrum diurnum L. of Potential Antiviral Activity against Human Corona 229-E Virus.

SARS-CoV-2 has caused more than 596 million infections and 6 million fatalities globally. Looking for urgent medication for prevention, treatment, and rehabilitation is obligatory. Plant extracts and green synthesized nanoparticles have numerous biological activities, including antiviral activity. HPLC analysis of C. dirnum L. leaf extract showed that catechin, ferulic acid, chlorogenic acid, and syringic acid were the most major compounds, with concentrations of 1425.16, 1004.68, 207.46, and 158.95 µg/g, respectively. Zinc nanoparticles were biosynthesized using zinc acetate and C. dirnum extract. TEM analysis revealed that the particle size of ZnO-NPs varied between 3.406 and 4.857 nm. An XRD study showed the existence of hexagonal crystals of ZnO-NPs with an average size of 12.11 nm. Both ZnO-NPs (IC50 = 7.01 and CC50 = 145.77) and C. dirnum L. extract (IC50 = 61.15 and CC50 = 145.87 µg/mL) showed antiviral activity against HCOV-229E, but their combination (IC50 = 2.41 and CC50 = 179.23) showed higher activity than both. Molecular docking was used to investigate the affinity of some metabolites against the HCOV-229E main protease. Chlorogenic acid, solanidine, and catchin showed high affinity (-7.13, -6.95, and -6.52), compared to the ligand MDP (-5.66 Kcal/mol). Cestrum dinurum extract and ZnO-NPs combination should be subjected to further studies to be used as an antiviral drug.

A review on 2D-ZnO nanostructure based biosensors: from materials to devices

During the COVID'19 outbreak, biosensing devices won increasing relevance, demonstrating their potential in the medical diagnostic field. Hence, the present review reports on the main advances in 2D-ZnO nanostructure-based biosensors. So far, bulk ZnO has shown potential for biosensing, optical, and power electronic applications, mainly based on its wide band gap. In the post graphene era, its 2-D allotropes like ZnO sheets and ZnO nanoribbons have outperformed the bulk ZnO structures for specific applications. ZnO demonstrates various stable and feasible morphologies: nanotubes, nanowires, nanorods, nanosheets, nanoparticles, and nanobelts. As a matrix layer in biosensing applications, ZnO strongly binds to biomolecules due to its high isoelectric point (IEP) and shows a strong sensitivity due to the high surface-to-volume ratio. Further, ZnO nanostructures used as a matrix layer play an important role in inhibiting specific biological interactions and hence improve the sensitivity of sensing devices. Further, bioselective layers are typically immobilized onto ZnO either by direct adsorption or by covalent binding. ZnO based biosensors are categorized into optical, piezoelectric, and electrochemical biosensors, among others, based on their biosensing mechanism. In particular, electrochemical sensors produce signals via an electrical pathway for detecting and monitoring the target molecules. Optical sensors produce signals based on luminescence or reflectance, among others. Piezoelectric biosensors produce signals by mass loading of the piezoelectric material. ZnO-based FET biosensors are also reported, showing sensing application by the change in the channel's conductance. Further, recent literature on the detection of COVID-19 using ZnO nanostructures is presented.

Investigating the Antibacterial Activity and Safety of Zinc Oxide Nanoparticles versus a Commercial Alcohol-Based Hand-Sanitizer: Can Zinc Oxide Nanoparticles Be Useful for Hand Sanitation?

Hand hygiene is the key factor to control and prevent the spread of infections, for example, hospital-acquired infections (HAIs). People commonly use alcohol-based hand sanitizers to assure hand hygiene. However, frequent use of alcohol-based hand sanitizers in a pandemic situation (e.g., COVID-19) was associated with serious drawbacks such as skin toxicity including irritation, skin dermatitis, and skin dryness or cracking, along with peeling, redness, or itching with higher possibility of infection. This demands the development of alternative novel products that are effective as alcohol-based hand sanitizers but have no hazardous effects. Zinc oxide nanoparticles (ZnO-NPs) are known to have broad-spectrum antimicrobial activity, be compatible with the biological system and the environment, and have applicable and economic industrial-scale production. Thus, ZnO-NPs might be a good candidate for hand sanitation. To the best of our knowledge, the antibacterial activity of ZnO-NPs in comparison to alcohol-based hand sanitizers has not yet been studied. In the present work, a comparative study of the antibacterial activity of ZnO-NPs vs. Sterillium, a commercial alcohol-based hand sanitizer that is commonly used in Egyptian hospitals, was performed against common microorganisms known to cause HAIs in Egypt, including Acinetobacter baumannii, Klebsiella pneumoniae, Methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus aureus. The safety profiles of ZnO-NPs and Sterillium were also assessed. The obtained results demonstrated the superior antibacterial activity and safety of ZnO-NPs compared to Sterillium. Therefore, ZnO-NPs could be a promising candidate for hand sanitation in comparison to alcohol-based hand sanitizers; however, several studies related to long-term toxicity and stability of ZnO-NPs and investigations into their antimicrobial activity and safety in healthcare settings are still required in the future to ascertain their antimicrobial activity and safety.

Antifungal Effect of Nanoparticles against COVID-19 Linked Black Fungus: A Perspective on Biomedical Applications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that has caused a 'coronavirus disease 2019' (COVID-19) pandemic in multiple waves, which threatens human health and public safety. During this pandemic, some patients with COVID-19 acquired secondary infections, such as mucormycosis, also known as black fungus disease. Mucormycosis is a serious, acute, and deadly fungal infection caused by Mucorales-related fungal species, and it spreads rapidly. Hence, prompt diagnosis and treatment are necessary to avoid high mortality and morbidity rates. Major risk factors for this disease include uncontrolled diabetes mellitus and immunosuppression that can also facilitate increases in mucormycosis infections. The extensive use of steroids to prevent the worsening of COVID-19 can lead to black fungus infection. Generally, antifungal agents dedicated to medical applications must be biocompatible, non-toxic, easily soluble, efficient, and hypoallergenic. They should also provide long-term protection against fungal growth. COVID-19-related black fungus infection causes a severe increase in fatalities. Therefore, there is a strong need for the development of novel and efficient antimicrobial agents. Recently, nanoparticle-containing products available in the market have been used as antimicrobial agents to prevent bacterial growth, but little is known about their efficacy with respect to preventing fungal growth, especially black fungus. The present review focuses on the effect of various types of metal nanoparticles, specifically those containing silver, zinc oxide, gold, copper, titanium, magnetic, iron, and carbon, on the growth of various types of fungi. We particularly focused on how these nanoparticles can impact the growth of black fungus. We also discussed black fungus co-infection in the context of the global COVID-19 outbreak, and management and guidelines to help control COVID-19-associated black fungus infection. Finally, this review aimed to elucidate the relationship between COVID-19 and mucormycosis.

In Silico Studies on Zinc Oxide Based Nanostructured Oil Carriers with Seed Extracts of Nigella sativa and Pimpinella anisum as Potential Inhibitors of 3CL Protease of SARS-CoV-2.

Coming into the second year of the pandemic, the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants continue to be a serious health hazard globally. A surge in the omicron wave, despite the discovery of the vaccines, has shifted the attention of research towards the discovery and use of bioactive compounds, being potential inhibitors of the viral structural proteins. The present study aimed at the green synthesis of zinc oxide (ZnO) nanoparticles with seed extracts of Nigella sativa and Pimpinella anisum-loaded nanostructured oil carriers (NLC)-using a mixture of olive and black seed essential oils. The synthesized ZnO NLC were extensively characterized. In addition, the constituent compounds in ZnO NLC were investigated as a potential inhibitor for the SARS-CoV-2 main protease (3CLpro or Mpro) where 27 bioactive constituents, along with ZnO in the nanostructure, were subjected to molecular docking studies. The resultant high-score compounds were further validated by molecular dynamics simulation. The study optimized the compounds dithymoquinone, δ-hederin, oleuropein, and zinc oxide with high docking energy scores (ranging from -7.9 to -9.9 kcal/mol). The RMSD and RMSF data that ensued also mirrored these results for the stability of proteins and ligands. RMSD and RMSF data showed no conformational change in the protein during the MD simulation. Histograms of every simulation trajectory explained the ligand properties and ligand-protein contacts. Nevertheless, further experimental investigations and validation of the selected candidates are imperative to take forward the applicability of the nanostructure as a potent inhibitor of COVID-19 (Coronavirus Disease 2019) for clinical trials.

Natural Rubber (NR) Latex Films with Antimicrobial Properties for Stethoscope Diaphragm Covers

Systematic disinfection of the stethoscope diaphragm is required to ensure that it does not act as a vector for cross-transmission of health-related diseases. Thus, an antimicrobial latex film could be used as a cover to inhibit pathogenic bacteria from growing on its surface. The aim of this work is to determine the antimicrobial activity and mechanical properties of antimicrobial natural rubber (NR) latex films with different types of antimicrobial agents (mangosteen peel powder (MPP), zinc oxide nanoparticles (ZnO NP), and povidone-iodine (PVP-I)). The antimicrobial loading was varied from 0.5, to 1.0, and 2.0 phr to monitor the effective inhibition of Gram-negative bacteria and fungi growth. For MPP and PVP-I antimicrobial agents, a loading of 2.0 phr showed good antimicrobial efficacy with the largest zone of inhibition. Simultaneously, ZnO NP demonstrated excellent antimicrobial activity at low concentrations. The addition of antimicrobial agents shows a comparable effect on the mechanical properties of NR latex films. In comparison to control NR latex film (29.41 MPa, 48.49 N/mm), antimicrobial-filled films have significantly greater tensile and tear strengths (MPP (33.84 MPa, 65.21 N/mm), ZnO NP (31.79 MPa, 52.77 N/mm), and PVP-I (33.25 MPa, 50.75 N/mm). In conclusion, the addition of antimicrobial agents, particularly ZnO NP, can be a better choice for NR latex films because they will serve as both an activator and an antimicrobial. In a clinical context, with regard to frequently used medical equipment such as a stethoscope, such an approach offers significant promise to aid infection control.

Development of Eco-Friendly Nanomembranes of Aloe vera/PVA/ZnO for Potential Applications in Medical Devices.

Due to the current COVID-19 pandemic, there is a crucial need for the development of antimicrobial and antiviral personal protective equipment such as facemasks and gowns. Therefore, in this research we fabricated electrospun nanofibers composite with polyvinyl alcohol, aloe vera, and zinc oxide nanoparticles for end application in medical devices. Electrospun nanofibers were made with varying concentrations of aloe vera (1%, 2%, 3%, 4%) having a constant concentration of ZnO (0.5%) with varying concentrations of ZnO nanoparticles (1%, 2%, 3%, 4%) having a constant concentration of aloe vera (0.5%). To check the morphology and composition, all prepared nanofibers were subjected to different characterization techniques, such as Scanning Electron Microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FTIR). In addition, its antimicrobial activity was checked both with qualitative and quantitative approaches against gram-positive (Staphylococcus aureus) bacteria and gram-negative (Escherichia coli) bacteria. The results suggest that increasing ZnO concentration kills and inhibits bacterial growth more proficiently compared to increasing aloe vera concentration in electrospun nanofibers; the highest antimicrobial was found with 4% ZnO, killing almost 100% of gram-positive (Staphylococcus aureus) bacteria and 99.2% of gram-negative (Escherichia coli) bacteria. These fabricated nanofibers have potential applications in medical devices and would help control the spread of many diseases.

Nanoformulation Composed of Ellagic Acid and Functionalized Zinc Oxide Nanoparticles Inactivates DNA and RNA Viruses.

The COVID-19 pandemic has strongly impacted daily life across the globe and caused millions of infections and deaths. No drug therapy has yet been approved for the clinic. In the current study, we provide a novel nanoformulation against DNA and RNA viruses that also has a potential for implementation against COVID-19. The inorganic-organic hybrid nanoformulation is composed of zinc oxide nanoparticles (ZnO NPs) functionalized with triptycene organic molecules (TRP) via EDC/NHS coupling chemistry and impregnated with a natural agent, ellagic acid (ELG), via non-covalent interactions. The physicochemical properties of prepared materials were identified with several techniques. The hybrid nanoformulation contained 9.5 wt.% TRP and was loaded with up to 33.3 wt.% ELG. ELG alone exhibited higher cytotoxicity than both the ZnO NPs and nanoformulation against host cells. The nanoformulation efficiently inhibited viruses, compared to ZnO NPs or ELG alone. For H1N1 and HCoV-229E (RNA viruses), the nanoformulation had a therapeutic index of 77.3 and 75.7, respectively. For HSV-2 and Ad-7 (DNA viruses), the nanoformulation had a therapeutic index of 57.5 and 51.7, respectively. In addition, the nanoformulation showed direct inactivation of HCoV-229E via a virucidal mechanism. The inhibition by this mechanism was > 60%. Thus, the nanoformulation is a potentially safe and low-cost hybrid agent that can be explored as a new alternative therapeutic strategy for COVID-19.

Green synthesis of zinc oxide nanoparticles using Anoectochilus elatus, and their biomedical applications.

Zinc and its derivatives requirement increased to enhance human immunity against the different pandemics, including covid-19. Green synthesis is an emerging field of research. Zinc oxide (ZnO) nanoparticles have been prepared from Anoectochilus elatus and characterized using absorption, vibrational and electron microscope analysis. They were carried for antibacterial, inflammatory control tendency, and potential antioxidant activities. The brine shrimp lethal assay tested the biologically derived nanomaterial toxicity and the lethal concentration (LC50) is 599.79 µg/ml. The inhibition against the important disease-causing pathogens was measured against four-gram negative, gram-positive bacteria and two fungus pathogens. The nanomaterial exposed inhibition zone for gram-positive bacteria between 17 mm and 25 mm. The inhibition zone against gram-negative bacteria exists between 19 mm and 24 mm. The anti-inflammatory activity was assessed by inhibition of protein denaturation and protease inhibitory activity using nanomaterial. The antioxidant activity was examined using four assays for the therapeutic activities. The average size range of 60-80 nm nanoparticles has prepared and exposed the good biological activity between 50 µg/ml and 100 µg/ml. The comparative results of anti-inflammatory and antioxidant assay results with standards such as Aspirin and vitamin C exposed that two to three times higher concentrations are required for the fifty percent of inhibitions. The prepared low-cost nanoparticle has exhibited excellent biological activity without any side effects and may enhance immunity.

Antiviral zinc oxide nanoparticles mediated by hesperidin and in silico comparison study between antiviral phenolics as anti-SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus (COVID-19), is the virus responsible for over 69,613,607 million infections and over 1,582,966 deaths worldwide. All treatment measures and protocols were considered to be supportive only and not curative. During this current coronavirus pandemic, searching for pharmaceutical or traditional complementary and integrative medicine to assist with prevention, treatment, and recovery has been advantageous. These phytopharmaceuticals and nutraceuticals can be more economic, available, safe and lower side effects. This is in silico comparison study of ten phenolic antiviral agents against SARS-CoV-2, as well as isolation of the most active metabolite from natural sources. Zinc oxide nanoparticles (ZnO NPs) were also then prepared using these metabolite as a reducing agent. All tested compounds showed predicted anti-SARS-CoV-2 activity. Hesperidin showed the highest docking score, this leads us to isolate it from the orange peels and we confirmed its structure by conventenional spectroscopic analysis. In addition, synthesis of hesperidin zinc oxide nanoparticles was characterized by UV, IR, XRD and TEM. In vitro antiviral activity of hesperidin and ZnO NPs was evaluated against hepatitis A virus as an example of RNA viruses. However, ZnO NPs and hesperidin showed antiviral activity against HAV but ZnO NPs showed higher activity than hesperidin. Thus, hesperidin and its mediated ZnO nanoparticles are willing antiviral agents and further studies against SARS-CoV-2 are required to be used as a potential treatment.