ArticlePDF Available

Instantaneous “catch‐and‐kill” inactivation of SARS‐CoV‐2 by nitride ceramics

Clinical and Translational Medicine

October 2020
10(6)

DOI:10.1002/ctm2.212

License
CC BY 4.0

Authors:

Giuseppe Pezzotti

Kyoto Institute of Technology

Masaharu Shin-Ya

Kyoto Prefectural University of Medicine

Show all 8 authorsHide

(A) TCID50/50 μL and % reduction plots by TCID50 assay (based on the Reed‐Muench method). (B) RT‐PCR tests to evaluate viral RNA using two sets of N gene primers; a comparison is given using evaluations of supernatants and powders with viral RNA from virions simply suspended in water. (C) Fluorescence micrographs inoculated VeroE6/TMPRSS2 cells after staining: red, green, and blue stains visualize viral protein, F‐actin, and cell nuclei, respectively. (D) Quantification of fluorescence microscopy data given as % infected cells on total cells, namely, the percent fraction of red‐stained cells with respect to the total number of blue‐stained nuclei, and the percent fraction of viable cells on total cells, namely, the percent fraction of green‐stained cells with respect to the total number of blue‐stained nuclei. Labels in inset specify statistics (unpaired two‐tailed Student's test with n = 3)

…

The “catch and kill” mechanism. Central panel: Draft of the electrochemical interaction between Si3N4 surface and SARS‐CoV‐2 virions (envelope and membrane proteins are electrostatically attracted at the negatively charged Si3N4 surface while protonated amines, which resemble cell lysine N‐terminal receptors, link with the spike protein and lock the virions; once the virion is “caught” and locked on the Si3N4 surface, eluted NH3 gas freely penetrates envelope proteins and “kills” it). Left panel: Draft of electrochemical “binding competitive” interactions between protonated amine groups on the surface of Si3N4 and lysine N‐terminals in cells. Right panel: RNA cleavage by ammonia species occurs in three successive steps including the deprotonation of backbone 2′‐hydroxyls, the formation of a transient pentaphosphate group, and the final RNA cleavage by alkaline transesterification

…

Figures - available from: Clinical and Translational Medicine

This content is subject to copyright. Terms and conditions apply.

Access to this full-text is provided by Wiley.

Learn more

Content available from Clinical and Translational Medicine

This content is subject to copyright. Terms and conditions apply.

Received: 24 September 2020 Revised: 5 October 2020 Accepted: 6 October 2020 Published online: 15 October 2020

DOI: 10.1002/ctm2.212

LETTER TO EDITOR

Instantaneous “catch-and-kill” inactivation of SARS-CoV-2

by nitride ceramics

Dear Editor,

We propose a nontoxic, sustainable alternative to con-

ventional surface disinfection, possibly useful in fighting

the present COVID-19 pandemics. The global spread of

COVID-19 has increased awareness of how the SARS-

CoV-2 virus is transmitted on surfaces.1Person to person

contagion can occur through contact with contaminated

surfaces. To limit this contagion pathway, regular surface

disinfection is recommended. Research indicates that

this virus can remain viable for 4 to 72 hours on plastic,

copper, and steel, and up to 7 days on surgical mask

material,2creating increased transmission risk in social

and medical environments. Presently, the application

of ethanol in combination with sodium hypochlorite

or hydrogen peroxide or the use of ultraviolet surface

irradiation effectively inactivates the virus. However, the

practical application of these methods, as well as other

antiviral protocols, is hindered by their toxic impact on

human health.3It is vital to develop surfaces, fabrics, and

other materials that could inherently inhibit viral spread

while concurrently being safe for humans.

One such material is silicon nitride (Si3N4), an FDA-

cleared bioceramic, which may be used in the human body.

It has superior antibacterial behavior and has been proven

safe for long-term use in humans. It possesses a unique sur-

face biochemistry that inhibits bacterial infections by long-

term elution of nitrogen (promptly converted into ammo-

nia) in minute concentrations that, unlike bacteria and

viruses, mammalian cells can easily metabolize.4Within 1

minute, influenza A and enterovirus were completely inac-

tivated by Si3N4bioceramic particles suspended in water.5

In this study, we exposed SARS-CoV-2 virions to the

above bioceramic as well as to aluminum nitride (AlN)

micrometric powders suspended in water. The nitrogen-

based ceramic, AlN, undergoes surface hydrolysis analo-

gous to that of Si3N4when in such a solution. We used two

controls, namely, a copper (Cu) particle suspension (a pos-

itive control, known to strongly inactivate pathogens and

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the

original work is properly cited.

viruses6) and a negative control expected to have no effect,

H2O. The supernatant virions were then inoculated into

VeroE6/TMPRSS2 cells. We expected comparable antiviral

behavior for Si3N4and AlN, as these nitride compounds

share the chemical similarity of N atoms with strong elec-

tronegativity.

Figure 1A shows results for TCID50 assay in case of viri-

ons exposed to Si3N4, AlN, and Cu powders in 15 wt.%

at 1-minute inactivation time. Compared with the water-

exposed negative control (sham sample), these three pow-

ders produced equally effective inactivation of SARS-CoV-

2 virions (>99%). We then examined fragmentation of viral

RNA upon 1-minute contact with the powders by means

of RT-PCR experiments on the virions N-gene sequence

(Figure 1B). Unlike the case of powder-unexposed con-

trol supernatant (sham sample), the viral RNA underwent

nearly complete fragmentation when exposed to Cu, and

was significantly damaged after both AlN and Si3N4con-

tact. Viral RNA on pelleted powders, after 1-minute expo-

sure, was not detectable for any of the three powders

(Figure 1B). Experiments repeated at 10-minute exposure

revealed substantial RNA cleavage for all powders tested

(see Supporting Information).

Figure 1C shows immunofluorescence imaging results

on inoculated cells. The envelope antibody of the

anti-SARS coronavirus stained red; viable cell F-actin

(phalloidin-stained) green; and cell nuclei (DAPI-stained)

blue. Micrographs showing fluorescence in Figure 1C com-

pare the sham (negative) control VeroE6/TMPRSS2 cell

population with populations inoculated with supernatant

virions exposed to Si3N4, AlN, and Cu (see labels). The

synthesis of viral protein, visualized by red-fluorescent

signals, imaged the sham sample cells extensively infected

by the virus. As expected, as-cultured VeroE6/TMPRSS2

cells unexposed to virions (mock sample) showed no

red staining. A striking result was that cells inoculated

with supernatant treated with Si3N4and, to a lesser

extent, with AlN, were viable and showed a low fraction

Clin. Transl. Med. 2020;10:e212. wileyonlinelibrary.com/journal/ctm2 1of4

https://doi.org/10.1002/ctm2.212

2of4 LETTER TO EDITOR

FIGURE 1 (A) TCID50/50 μL and % reduction plots by TCID50 assay (based on the Reed-Muench method). (B) RT-PCR tests to evaluate

viral RNA using two sets of N gene primers; a comparison is given using evaluations of supernatants and powders with viral RNA from virions

simply suspended in water. (C) Fluorescencemicrographs inoculated VeroE6/TMPRSS2 cells after staining: red, green, and blue stains visualize

viral protein, F-actin, and cell nuclei, respectively. (D) Quantification of fluorescence microscopy data given as % infected cells on total cells,

namely, the percent fraction of red-stained cells with respect to the total number of blue-stained nuclei, and the percent fraction of viable cells

on total cells, namely, the percent fraction of green-stained cells with respect to the total number of blue-stained nuclei. Labels in inset specify

statistics (unpaired two-tailed Student’s test with n =3)

of infected cells. On the other hand, cells infected with

Cu-treated viral supernatant were essentially dead (see

complete lack of F-actin), clearly indicating that it was

free copper ions in the cells having toxic effects, and not

viral infection, that caused cell death.7We confirmed this

using in situ Raman spectroscopy (see Supporting Infor-

mation). In a quantitative plot of fluorescence microscopy

results (Figure 1D), ∼35% fraction of cells in the sham

sample (negative control) were infected. Comparatively,

cells inoculated with Si3N4supernatants showed only

2% infection and with AlN supernatants showed 8%

infection (see Supporting Information for experimental

procedures).

Our work revealed two pivotal aspects of Si3N4sur-

face chemistry that likely play fundamental roles in

inactivating SARS-CoV-2: (a) protonation of the amino

groups creates Si3N4surface sites Si–NH3+that resem-

ble N-terminals of lysine, C–NH3+, the cell side viral

receptor; and, (b) hydrolytically eluted ammonia from

the Si3N4surface as a strong virucidal compound.

Figure 2(center) draws the interaction between virus and

bioceramic surface in aqueous environment. At pH 7.4,

positively charged viral envelope/membrane proteins are

strongly attracted to the Si3N4surface (see Supporting

Information). The left panel depicts similarity between

protonated amine and the lysine N-terminal. As is the

case with hepatitis B and influenza A,5,8 an extremely

effective “competitive binding” effect on SARS-CoV-2

occurs. Once in contact with the virus, eluted ammonia

gas penetrates the virions and cuts through the RNA

backbone9(see Figure 2, right panel). The combination of

RT-PCR results and fluorescence microscopy suggest that

SARS-CoV-2 inactivation takes place through a sequence

of events: virions are first electrically trapped, locked

by “competitive binding,” and then killed by “ammonia

poisoning.” Such a scenario could be referred to as “catch

and kill.”

Results confirm SARS-CoV-2 inactivation was almost

instantaneous upon contact with Cu, AlN, and Si3N4,but

only the latter compound proved completely safe to host

cells. The bioceramic, Si3N4, is thus a primary candidate to

replace toxic and allergenic compounds in long-term envi-

ronmental sanitation.10 The use of micron-sized Si3N4par-

ticles in disinfectant sprays or their direct embedment in

personal protective equipment fabrics (facemasks, surgical

drapes, and other garments) in hospitals could limit viral

LETTER TO EDITOR 3of4

FIGURE 2 The “catch and kill” mechanism. Central panel: Draft of the electrochemical interaction between Si3N4surface and SARS-

CoV-2 virions (envelope and membrane proteins are electrostatically attracted at the negatively charged Si3N4surface while protonated amines,

which resemble cell lysine N-terminal receptors, link with the spike protein and lock the virions; once the virion is “caught” and locked on

the Si3N4surface, eluted NH3gas freely penetrates envelope proteins and “kills” it). Left panel: Draft of electrochemical “binding competitive”

interactions between protonated amine groups on the surface of Si3N4and lysine N-terminals in cells. Right panel: RNA cleavage by ammonia

species occurs in three successive steps including the deprotonation of backbone 2′-hydroxyls, the formation of a transient pentaphosphate

group, and the final RNA cleavage by alkaline transesterification

transmission for both health workers and patients. As nei-

ther anion- nor cation-side surface chemistry of Si3N4will

affect human health, even in the long term, this bioceramic

has potential as an invaluable tool in fighting the SARS-

CoV-2 pandemic.

Giuseppe Pezzotti1,2

Eriko Ohgitani2

Masaharu Shin-Ya2

Tetsuya Adachi3

Elia Marin1,3

Francesco Boschetto1,3

Wenliang Zhu1

Osam Mazda2

1Ceramic Physics Laboratory, Kyoto Institute of

Technology, Kyoto, Japan

2Department of Immunology, Graduate School of Medical

Science, Kyoto Prefectural University of Medicine, Kyoto,

Japan

3Department of Dental Medicine, Graduate School of

Medical Science, Kyoto Prefectural University of Medicine,

Kyoto, Japan

Correspondence

Giuseppe Pezzotti, Ceramic Physics Laboratory, Kyoto

Institute of Technology, Sakyo-ku, Matsugasaki, Kyoto

606–8585, Japan.

Email: pezzotti@kit.ac.jp

Osam Mazda, Department of Immunology, Graduate

School of Medical Science, Kyoto Prefectural University

of Medicine, Kyoto, Japan.

Email: mazda@koto.kpu-m.ac.jp

ORCID

Giuseppe Pezzotti https://orcid.org/0000-0002-9663-

2429

REFERENCES

1. Kampf G, Todt D, Pfaender S, Steinmann E. Persistence

of coronaviruses on inanimate surfaces and their inac-

tivation with biocidal agents. J Hosp Infect.2020;104:

246-251.

2. Warnes SL, Little ZR, Keevil CW. Human coronavirus 229E

remains infectious on common touch surface materials. MBio.

2015;6:1-10.

4of4 LETTER TO EDITOR

3. Chin A, Chu J, Perera M, et al. Stability of SARS-CoV-2 in dif-

ferent environmental conditions. medRxivorg.2020;5247.https:

//doi.org/10.1101/2020.03.15.20036673.

4. Pezzotti G, Nitride S. A bioceramic with a gift. ACS Appl Mater

Interfaces. 2019;11:26619-26636.

5. Pezzotti G, et al. Sci Rep. 2020. under review.

6. Grass G, Rensing C, Solioz M. Metallic copper as an

antimicrobial surface. Appl Environ Microbiol.2011;77:

1541-1547.

7. Balamurugan K, Schaffner W. Copper homeostasis in eukary-

otes: teetering on a tightrope. Biochim Biophys Acta – Mol Cell

Res. 2006;1763:737-746.

8. Ye X, et al. Sci Rep. 2016;6:1-11.

9. Decrey L, Kazama S, Udert KM, Kohn T. Ammonia as an in situ

sanitizer: inactivation kinetics and mechanisms of the ssRNA

virus MS2 by NH3.Environ Sci Technol. 2015;49:1060-1067.

10. Scholar PG. Eur J Pharm Med Res. 2018;5:232-237.

SUPPORTING INFORMATION

Additional supporting information may be found online

in the Supporting Information section at the end of the

article.

Available via license: CC BY

Content may be subject to copyright.

Instantaneous Inactivation of Herpes Simplex Virus by Silicon Nitride Bioceramics

Article

Full-text available

Aug 2023
INT J MOL SCI

Hydrolytic reactions taking place at the surface of a silicon nitride (Si3N4) bioceramic were found to induce instantaneous inactivation of Human herpesvirus 1 (HHV-1, also known as Herpes simplex virus 1 or HSV-1). Si3N4 is a non-oxide ceramic compound with strong antibacterial and antiviral properties that has been proven safe for human cells. HSV-1 is a double-stranded DNA virus that infects a variety of host tissues through a lytic and latent cycle. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) tests of HSV-1 DNA after instantaneous contact with Si3N4 showed that ammonia and its nitrogen radical byproducts, produced upon Si3N4 hydrolysis, directly reacted with viral proteins and fragmented the virus DNA, irreversibly damaging its structure. A comparison carried out upon testing HSV-1 against ZrO2 particles under identical experimental conditions showed a significantly weaker (but not null) antiviral effect, which was attributed to oxygen radical influence. The results of this study extend the effectiveness of Si3N4’s antiviral properties beyond their previously proven efficacy against a large variety of single-stranded enveloped and non-enveloped RNA viruses. Possible applications include the development of antiviral creams or gels and oral rinses to exploit an extremely efficient, localized, and instantaneous viral reduction by means of a safe and more effective alternative to conventional antiviral creams. Upon incorporating a minor fraction of micrometric Si3N4 particles into polymeric matrices, antiherpetic devices could be fabricated, which would effectively impede viral reactivation and enable high local effectiveness for extended periods of time.

Milk Casein Inhibits Effect of Black Tea Galloylated Theaflavins to Inactivate SARS-CoV-2 In Vitro

Article

Full-text available

Sep 2023

Continuing caution is required against the potential emergence of SARS-CoV-2 novel mutants that could pose the next global health and socioeconomical threats. If virus in saliva can be inactivated by a beverage, such a beverage may be useful because the saliva of infected persons is the major origin of droplets and aerosols that mediate human-to-human viral transmission. We previously reported that SARS-CoV-2 was significantly inactivated by treatment in vitro with tea including green tea and black tea. Catechins and its derived compounds galloylated theaflavins (gTFs) bound to the receptor-binding domain (RBD) of the S-protein and blocked interaction between RBD and ACE2. Black tea is often consumed with sugar, milk, lemon juice, etc., and it remains unclarified whether these ingredients may influence the anti-SARS-CoV-2 effect of black tea. Here, we examined the effect of black tea on Omicron subvariants in the presence of these ingredients. The infectivity of Omicron subvariants was decreased to 1/100 or lower after treatment with black tea for 10 s. One or two teaspoons of milk (4~8 mL) completely blocked the anti-viral effect of a cup of tea (125 mL), whereas an addition of sugar or lemon juice failed to do so. The suppressive effect was dose-dependently exerted by milk casein but not whey proteins. gTFs were coprecipitated with casein after acidification of milk-supplemented black tea, strongly suggesting the binding of gTFs to casein. The present study demonstrates for the first time that an addition of milk cancelled the anti-SARS-CoV-2 effect of black tea due to binding of casein to gTFs.

The Antipathogenic Properties of Silicon Nitride

Chapter

Oct 2024

Silicon nitride demonstrates exceptional biocompatibility in experimental studies. These data have supported its use in human spinal fusion implants where excellent clinical outcomes include a possible reduction in infection risk. This observation relates to an intriguing property of silicon nitride—its remarkable ability to eradicate bacteria, viruses, and fungi while being safe enough to use as an implant. As described in this chapter, several experimental investigations have shown that silicon nitride exhibits potent antibacterial activity against a variety of bacterial strains, including gram-positive and gram-negative species. This effect arises from a surface chemical reaction that releases nitrogen moieties that are converted to reactive nitrogen species that, in turn, disrupt prokaryotic cell membranes and metabolic processes, and cause cell lysis. Similar mechanisms explain the antiviral efficacy of silicon nitride against several viruses. In vitro studies have shown nearly instantaneous viral inactivation upon contact, including several variants of the SARS-CoV-2 virus. The antipathogenic effects of silicon nitride extend to fungi, such as Candida albicans, a common dental pathogen. Silicon nitride’s antifungal activity is also due to the release of reactive nitrogen species that disrupt fungal cell membranes and inhibit biofilm formation. This antifungal effect manifests itself against Plasmopara viticola, an agricultural fungus that infects grape plants. In summary, the surface chemistry that explains silicon nitride’s osteopromotive properties also contributes to its ability to resist bacteria, viruses, and fungi. Further research into this area will hopefully lead to new strategies to combat infections and surface contamination, thereby discouraging the spread of human infectious diseases.

A Critical Review of Two Bioceramics for Total Hip Arthroplasty

Chapter

Oct 2024

Ceramic materials have played an important role in the development of modern total hip replacements. Following the introduction of the modular low-friction total hip (THA) in the 1960s, subsequent improvements have addressed the various failure modes for this prosthetic implant. Over the past two decades, clinical practitioners have generally moved away from hard-on-hard articulation couples (i.e., metal-on-metal or ceramic-on-ceramic (CoC)) to hard-on-soft bearing pairs (i.e., ceramic or metal on advanced polyethylene). Zirconia-toughened alumina (ZTA) femoral heads have emerged as a preferred choice due to their demonstrably improved strength, toughness, and polyethylene wear resistance, as supported by significant clinical data. Yet, despite these advancements, the longevity of modern THA has not improved significantly over that of the earliest cemented hip systems. This review chapter compares the performance of two biomaterials, ZTA and silicon nitride, for use in total hip arthroplasty. While silicon nitride currently lacks clinical data in THA due to its FDA approval for spinal fusion devices only, in vitro studies suggest potential advantages. These include the possible development of future THA designs that exceed the lifespan of young, active patients, and potentially reduce the need for revision surgeries due to polyethylene wear, deep infections, and other complications typically encountered after 15–20 years of service. The mechanical properties of silicon nitride femoral heads are at least as favorable as ZTA, with greater resistance to hydrothermally induced degradation. Silicon nitride also has a bioactive surface chemistry that makes the material highly biocompatible, and resistant to bacterial infection. In articulation against the most advanced polyethylene liner, silicon nitride exhibits wear properties comparable to, if not superior to ZTA. Additionally, it possesses the potential to mitigate long-term polyethylene oxidation and embrittlement, a contributing factor to THA failure. While ZTA femoral heads boast established clinical success, advancements in bearing materials are crucial for extending THA longevity to match the lifespans of the most demanding patients. In this context, silicon nitride emerges as a promising candidate, supported by its favorable in vitro performance.

Processing of Silicon Nitride Bioceramics

Chapter

Oct 2024

Bryan Jay McEntire

Due to its tailorable composition and microstructure, silicon nitride (Si3N4) has emerged as a promising material with diverse applications ranging from precision high-speed bearings to biomedical implants. This review explores the manufacturing processes for silicon nitride components, highlighting key production methods such as reaction bonding (RBSN), hot-pressing (HPSN), sintering (SSN), gas-pressure sintering (GPSN), and hot-isostatic pressing (HIPSN). RBSN is a legacy, but still a frequently used process that involves the in situ nitridation of pre-formed silicon shapes. More recent processes require synthesized Si3N4 powders as the starting raw material. Powder synthesis methods include direct silicon powder nitridation, carbothermal silica reduction, and diimide decomposition, with the latter offering exceptional quality for biomedical implants. Upon receipt of Si3N4 raw materials, multiple additional manufacturing steps are required to produce useful components. Various types and amounts of sintering aids are combined with the Si3N4 powder, followed by mixing or comminution. Aqueous-based slurries are often employed to improve homogeneity, followed by spray- or freeze-drying. Component forming occurs by several methods, including dry- or isostatic-pressing, slip- or pressure-casting, extrusion, injection molding, and various additive manufacturing techniques. Densification is accomplished using any number of the aforementioned methods, but it is important to note that each technique has its own specific parameters and process requirements. Additional steps such as machining, polishing, proof testing, and non-destructive evaluation are well-established production or inspection processes. In vitro and in vivo animal studies demonstrate silicon nitride’s biocompatibility and its ability to promote osteoprogenitor cell differentiation and healing. These findings are further supported by clinical data on silicon nitride spinal fusion implants. Continuous research and clinical advancements position silicon nitride as a crucial biomaterial with the potential to significantly improve human health and functional outcomes.

The Future of Silicon Nitride: Biomedical Applications and Beyond

Chapter

Oct 2024

This closing chapter highlights silicon nitride’s continued development, clinical translation, and industrial adoption (Si3N4). The surface chemistry of Si3N4, addressed in earlier chapters makes it truly “a bioceramic with a gift” that has a positive impact on mammalian cells and a negative impact on pathogens such as bacteria, fungi, and viruses. While the adoption of Si3N4 into biomedical implants is still early, the material is attracting attention for its unique combination of biocompatibility, osteoconductivity, and antibacterial properties. Going further, Si3N4’s hardness and wear resistance make it suitable for implants that replace diseased hip, knee, and shoulder joints, as well as high-performance surgical instruments such as dental drills. In these applications, Si3N4’s high-fracture toughness, strength, hardness, wear resistance, and low-friction coefficient are ideal. Si3N4 is friendly toward all radiographic imaging modalities, with minimal to no image distortion, facilitating accurate placement and monitoring of implants. Si3N4’s antipathogenic properties will likely find application in wound dressings, antimicrobial filters that decrease viral propagation, antifungal agents, antimicrobial surfaces in public-use places, and antimicrobial fabrics for surgical gowns, masks, and drapes. Preliminary research has already set forth the foundation for these antimicrobial applications. Future Si3N4 applications will also likely address brain-computer interfaces, neural prosthetics, and bone replacements in neurosurgery. Biodegradable Si3N4 particles could target drug delivery to remote anatomic sites. Beyond healthcare, Si3N4 is already used widely in industrial and aerospace applications, and will likely have future uses in quantum computing, and beyond. Hopefully, this closing chapter will encourage collaboration across research, engineering, and technical teams to come up with rewarding discoveries and scientific achievements.

Raman Multi-Omic Snapshot and Statistical Validation of Structural Differences between Herpes Simplex Type I and Epstein–Barr Viruses

Article

Full-text available

Oct 2023
INT J MOL SCI

Raman spectroscopy was applied to study the structural differences between herpes simplex virus Type I (HSV-1) and Epstein–Barr virus (EBV). Raman spectra were first collected with statistical validity on clusters of the respective virions and analyzed according to principal component analysis (PCA). Then, average spectra were computed and a machine-learning approach applied to deconvolute them into sub-band components in order to perform comparative analyses. The Raman results revealed marked structural differences between the two viral strains, which could mainly be traced back to the massive presence of carbohydrates in the glycoproteins of EBV virions. Clear differences could also be recorded for selected tyrosine and tryptophan Raman bands sensitive to pH at the virion/environment interface. According to the observed spectral differences, Raman signatures of known biomolecules were interpreted to link structural differences with the viral functions of the two strains. The present study confirms the unique ability of Raman spectroscopy for answering structural questions at the molecular level in virology and, despite the structural complexity of viral structures, its capacity to readily and reliably differentiate between different virus types and strains.

Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2

Article

Full-text available

Oct 2023

The Omicron subvariants of SARS-CoV-2 have multiple mutations in the S-proteins and show high transmissibility. We previously reported that tea catechin (−)-epigallocatechin gallate (EGCG) and its derivatives including theaflavin-3,3’-di-O-digallate (TFDG) strongly inactivated the conventional SARS-CoV-2 by binding to the receptor binding domain (RBD) of the S-protein. Here we show that Omicron subvariants were effectively inactivated by green tea, Matcha, and black tea. EGCG and TFDG strongly suppressed infectivity of BA.1 and XE subvariants, while effect on BA.2.75 was weaker. Neutralization assay showed that EGCG and TFDG inhibited interaction between BA.1 RBD and ACE2. In silico analyses suggested that N460K, G446S and F490S mutations in RBDs crucially influenced the binding of EGCG/TFDG to the RBDs. Healthy volunteers consumed a candy containing green tea or black tea, and saliva collected from them immediately after the candy consumption significantly decreased BA.1 virus infectivity in vitro. These results indicate specific amino acid substitutions in RBDs that crucially influence the binding of EGCG/TFDG to the RBDs and different susceptibility of each Omicron subvariant to EGCG/TFDG. The study may suggest molecular basis for potential usefulness of these compounds in suppression of mutant viruses that could emerge in the future and cause next pandemic.

Silicon nitride as a biomaterial

Article

Full-text available

Aug 2023

Giuseppe Pezzotti

Three decades of research in the last century developed silicon nitride (Si3N4) as one of the strongest and toughest ceramic material for structural applications; but in this century, we newly discovered its gifted surface biochemistry. In an aqueous environment, Si3N4 undergoes surface hydrolysis with the slow but continuous elution of both silicon and nitrogen. A unique environment is created, which greatly enhances healing of soft and osseous tissues, inhibits bacterial biofilm formation, and eradicates viruses. The discovery of Si3N4’s biochemistry opens new paths in a wide array of different disciplines inside and outside of the physical body, including orthopedics, dentistry, virology, agronomy, and environmental remediation. In the biomedical field, it paves the way for a new generation of monolithic, composite, or coated implants for bone healing, including spinal arthrodesis, joint arthroplasty, craniomaxillofacial and dental devices. This review describes Si3N4’s surface chemistry in an aqueous environment in comparison with oxide ceramics. It discusses the pH-dependent elution kinetics of ammonia and ammonium as the main phenomenon behind its unparalleled behavior and demonstrates its friendly nature to mammalian cells while concurrently lysing invasive pathogens. Finally, a wider perspective is offered for future applications of Si3N4 in disease diagnosis and therapies, personal healthcare, agriculture, food and water safety, and environmental protection.

Preparation of AlN–Al2O3 composites exhibiting antibacterial and water purification properties

Article

Jun 2023
J EUR CERAM SOC

Stability of SARS-CoV-2 in different environmental conditions – Authors' reply

Article

Full-text available

Aug 2020

Stability of SARS-CoV-2 in different environmental conditions

Article

Full-text available

Apr 2020

Stability of SARS-CoV-2 in different environmental conditions

Preprint

Full-text available

Mar 2020

Stability of SARS-CoV-2 in different environmental conditions.

Terrestrial mountain islands and Pleistocene climate fluctuations as motors for speciation: A case study on the genus Pseudovelia (Hemiptera: Veliidae)

Article

Full-text available

Sep 2016

This study investigated the influences of geographic isolation and climate fluctuation on the genetic diversity, speciation, and biogeography of the genus Pseudovelia (Hemiptera: Veliidae) in subtropical China and tropic Indo-China Peninsula. Species nucleotide and haplotype diversities decreased with reduction in species distribution limits. The gene tree was congruent with the taxonomy of monophyly, except for four species, P. contorta, P. extensa, P. tibialis tibialis, and P. vittiformis. The conflicts between the genes and species tree could be due to long-term isolation and incomplete lineage sorting. Diversification analysis showed that the diversification rate (0.08?sp/My shifted to 0.5?sp/My) changed at 2.1?Ma, which occurred in the early Pleistocene period. Ancestral area reconstruction suggested that subtropical species possibly evolved from the tropics region (i.e., Indo-China Peninsula). Results implied that narrow endemics harbored relatively low genetic diversity because of small effective population and genetic drift. Radiation of subtropical Pseudovelia species was rapidly promoted by Pleistocene climate fluctuations and geographic isolation. The acute rising of the Hengduan Mountain with the entire uplift of the Qinghai-Tibet Plateau induced the initial differentiation of Pseudovelia species. These results highlighted the importance of geographical isolation and climate changes in promoting speciation in mountain habitat islands.

Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials

Article

Full-text available

Nov 2015

Importance: Respiratory viruses are responsible for more deaths globally than any other infectious agent. Animal coronaviruses that "host jump" to humans result in severe infections with high mortality, such as severe acute respiratory syndrome (SARS) and, more recently, Middle East respiratory syndrome (MERS). We show here that a closely related human coronavirus, 229E, which causes upper respiratory tract infection in healthy individuals and serious disease in patients with comorbidities, remained infectious on surface materials common to public and domestic areas for several days. The low infectious dose means that this is a significant infection risk to anyone touching a contaminated surface. However, rapid inactivation, irreversible destruction of viral RNA, and massive structural damage were observed in coronavirus exposed to copper and copper alloy surfaces. Incorporation of copper alloy surfaces in conjunction with effective cleaning regimens and good clinical practice could help to control transmission of respiratory coronaviruses, including MERS and SARS.

Metallic Copper as an Antimicrobial Surface

Article

Full-text available

Dec 2010
APPL ENVIRON MICROB

Bacteria, yeasts, and viruses are rapidly killed on metallic copper surfaces, and the term "contact killing" has been coined for this process. While the phenomenon was already known in ancient times, it is currently receiving renewed attention. This is due to the potential use of copper as an antibacterial material in health care settings. Contact killing was observed to take place at a rate of at least 7 to 8 logs per hour, and no live microorganisms were generally recovered from copper surfaces after prolonged incubation. The antimicrobial activity of copper and copper alloys is now well established, and copper has recently been registered at the U.S. Environmental Protection Agency as the first solid antimicrobial material. In several clinical studies, copper has been evaluated for use on touch surfaces, such as door handles, bathroom fixtures, or bed rails, in attempts to curb nosocomial infections. In connection to these new applications of copper, it is important to understand the mechanism of contact killing since it may bear on central issues, such as the possibility of the emergence and spread of resistant organisms, cleaning procedures, and questions of material and object engineering. Recent work has shed light on mechanistic aspects of contact killing. These findings will be reviewed here and juxtaposed with the toxicity mechanisms of ionic copper. The merit of copper as a hygienic material in hospitals and related settings will also be discussed.

Persistence of coronaviruses on inanimate surfaces and its inactivation with biocidal agents

Article

Feb 2020
J HOSP INFECT

Currently, the emergence of a novel human coronavirus, temporary named 2019-nCoV, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for 2019-nCoV, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread. FREE ACCESS ON JOURNAL HOMEPAGE

Silicon Nitride: A Bioceramic with a Gift

Article

Jun 2019

Giuseppe Pezzotti

Silicon nitride (Si3N4) has been recently recognized for its peculiar surface chemistry for medical applications. When immersed in an aqueous environment, the slow elution of silicon and nitrogen from its surface enhances healing of soft and osseous tissue, inhibits bacterial biofilm formation, and eradicates viruses. These benefits permit it to be used in a wide array of different disciplines inside and outside of the human body including orthopedics, dentistry, virology, agronomy, and environmental remediation. Given the global public health threat posed by mutating viruses and bacteria, silicon nitride offers a valid and straightforward alternative approach to fighting these pathogens. However, there is a conundrum behind these recent discoveries: How can this unique bioceramic be both friendly to mammalian cells while concurrently lysing invasive pathogens? This unparalleled characteristic can be explained by the pH-dependent kinetics of two ammonia species – NH4+ and NH3 – both of which are leached from the wet Si3N4 surface.

Ammonia as an In Situ Sanitizer: Inactivation Kinetics and Mechanisms of the ssRNA Virus MS2 by NH 3

Article

Dec 2014

Sanitizing human and animal waste (e.g., urine, fecal sludge, or grey water) is a critical step in reducing the spread of disease and ensuring microbially safe reuse of waste materials. Viruses are particularly persistent pathogens and can be transmitted through inadequately sanitized waste. However, adequate storage or digestion of waste can strongly reduce the number of viruses due to increases in pH and uncharged aqueous ammonia (NH3), a known biocide. In this study we investigated the kinetics and mechanisms of inactivation of the single-stranded RNA virus MS2 under temperature, pH and NH3 conditions representative of waste storage. MS2 inactivation was mainly controlled by the activity of NH3 over a pH range of 7.0-9.5 and temperatures lower than 40 °C. Other bases (e.g., hydroxide, carbonate) additionally contributed to the observed reduction of infective MS2. The loss in MS2 infectivity could be rationalized by a loss in genome integrity, which was attributed to genome cleavage via alkaline transesterification. The contribution of each base to genome transesterification, and hence inactivation, could be related to the base pKa by means of a Bronsted relationship. The Bronsted relationship in conjunction with the activity of bases in solution enabled an accurate prediction of MS2 inactivation rates.

Copper homeostasis in eukaryotes: Teetering on a tightrope

Article

Aug 2006
Biochim Biophys Acta

The transition metal copper is an essential trace element for both prokaryotes and eukaryotes. However, intracellular free copper has to be strictly limited due to its toxic side effects, not least the generation of reactive oxygen species (ROS) via redox cycling. Thus, all organisms have sophisticated copper homeostasis mechanisms that regulate uptake, distribution, sequestration and export of copper. From insects to mammals, metal-responsive transcription factor (MTF-1), a zinc finger transcription factor, controls expression of metallothioneins and other components involved in heavy metal homeostasis. In the fruit fly Drosophila, MTF-1 paradoxically acts as an activator under both high and low copper concentrations. Namely, under high copper conditions, MTF-1 activates metallothioneins in order to protect the cell, while under low copper conditions MTF-1 activates the copper importer Ctr1B in order to acquire scarce copper from the surroundings. This review highlights the current knowledge of copper homeostasis in eukaryotes with a focus on Drosophila and the role of MTF-1.

Instantaneous “catch‐and‐kill” inactivation of SARS‐CoV‐2 by nitride ceramics

Figures

Recommended publications

Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride

Silicon nitride: a potent solid-state bioceramic inactivator of ssRNA viruses

Mechanisms of instantaneous inactivation of SARS-CoV-2 by silicon nitride bioceramic

Surface functionalization of PEEK with silicon nitride