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



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Received: 24 September 2020 Revised: 5 October 2020 Accepted: 6 October 2020 Published online: 15 October 2020
DOI: 10.1002/ctm2.212
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.
© 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics
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-
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. 1of4
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
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
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,
3Department of Dental Medicine, Graduate School of
Medical Science, Kyoto Prefectural University of Medicine,
Kyoto, Japan
Giuseppe Pezzotti, Ceramic Physics Laboratory, Kyoto
Institute of Technology, Sakyo-ku, Matsugasaki, Kyoto
606–8585, Japan.
Osam Mazda, Department of Immunology, Graduate
School of Medical Science, Kyoto Prefectural University
of Medicine, Kyoto, Japan.
Giuseppe Pezzotti
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:
2. Warnes SL, Little ZR, Keevil CW. Human coronavirus 229E
remains infectious on common touch surface materials. MBio.
3. Chin A, Chu J, Perera M, et al. Stability of SARS-CoV-2 in dif-
ferent environmental conditions. medRxivorg.2020;5247.https:
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:
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.
Additional supporting information may be found online
in the Supporting Information section at the end of the
... In previous papers [20][21][22], micrometric silicon nitride (Si 3 N 4 ) bioceramic particles were shown to be capable of instantaneously inactivating, upon contact, a host of different RNA viruses, including influenza strains, enteroviruses, caliciviruses, and several SARS-CoV-2 variants. Unlike ethanol (often used in combination with sodium hypochlorite), hydrogen peroxide, and ultraviolet light, the most popular virus-inactivating agents [12,17,23], the Si 3 N 4 antiviral chemistry presents the unique advantage of being completely compatible with human cells. ...
... Unlike ethanol (often used in combination with sodium hypochlorite), hydrogen peroxide, and ultraviolet light, the most popular virus-inactivating agents [12,17,23], the Si 3 N 4 antiviral chemistry presents the unique advantage of being completely compatible with human cells. Accordingly, Si 3 N 4 can continuously be used in contact with tissues and has been proposed as an alternative surface disinfectant against COVID-19 [20,21]. The discovery of the antiviral properties of Si 3 N 4 [20][21][22] added important functionality to the application of this non-oxide ceramic as a biomaterial [24,25]. ...
... Accordingly, Si 3 N 4 can continuously be used in contact with tissues and has been proposed as an alternative surface disinfectant against COVID-19 [20,21]. The discovery of the antiviral properties of Si 3 N 4 [20][21][22] added important functionality to the application of this non-oxide ceramic as a biomaterial [24,25]. ...
Full-text available
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.
... The differences in the molecular structure and symmetry between the SARS-CoV-2 Japanese isolate and the two sub-types of the Alpha variant were stunningly bold. In two additional studies, 12,13 we have proposed the exploitation of the surface chemistry of silicon nitride bioceramics in an aqueous environment as an instantaneous and powerful antiviral effect against SARS-CoV-2. Unlike other solid-state antiviral agents, 14 Si 3 N 4 is a compound fully biocompatible toward eukaryotic cells while effectively counteracting pathogens. ...
... Since ssRNA virions have no capacity to resist ammonia attack to their RNA and viral proteins, 19,20 they become instantaneously inactivated by the presence of a few volume percent of micrometer-sized Si 3 N 4 particles in aqueous solution. 12,13,15 This paper builds upon our previous studies of the SARS-CoV-2 virus with a new twofold purpose: (i) to extend the Raman spectroscopic identification of the virus to the Delta variant (TY11-927) found in Japan, as distinct from the Japanese Kappa isolate, and (ii) to test the viral inactivation activity of the Si 3 N 4 micrometric powder against the Delta variant, while delving into the molecular chemistry mechanisms behind its instantaneous inactivation pathway. Accordingly, we focus here on the confirmation of a direct link between Raman light and key structure/symmetry characteristics of virions' molecular structure as chemical fingerprints for different variants and degenerative effects on SARS-CoV-2 virions. ...
... Compared with the negative control (sham sample), the Si 3 N 4 powder produced 99.85% effective inactivation of SARS-CoV-2 TY11-927 virions. This result was similar to that previously reported for the JPN/TY/WK-521 variant with an effective inactivation of 99.28%.12,13 The combination of the TCID 50 assay, RT-PCR, and fluorescence spectroscopy results provides unequivocal evidence for the occurrence of SARS-CoV-2 Delta variant inactivation by Si 3 N 4 bioceramic powder. ...
Raman spectroscopy uncovered molecular scale markers of the viral structure of the SARS-CoV-2 Delta variant and related viral inactivation mechanisms at the biological interface with silicon nitride (Si3N4) bioceramics. A comparison of Raman spectra collected on the TY11-927 variant (lineage B.1.617.2; simply referred to as the Delta variant henceforth) with those of the JPN/TY/WK-521 variant (lineage B.1.617.1; referred to as the Kappa variant or simply as the Japanese isolate henceforth) revealed the occurrence of key mutations of the spike receptor together with profound structural differences in the molecular structure/symmetry of sulfur-containing amino acid and altered hydrophobic interactions of the tyrosine residue. Additionally, different vibrational fractions of RNA purines and pyrimidines and dissimilar protein secondary structures were also recorded. Despite mutations, hydrolytic reactions at the surface of silicon nitride (Si3N4) bioceramics induced instantaneous inactivation of the Delta variant at the same rate as that of the Kappa variant. Contact between virions and micrometric Si3N4 particles yielded post-translational deimination of arginine spike residues, methionine sulfoxidation, tyrosine nitration, and oxidation of RNA purines to form formamidopyrimidines. Si3N4 bioceramics proved to be a safe and effective inorganic compound for instantaneous environmental sanitation.
... In total, 1 mole of AlN reacts with 3 mole of water and produces 1 mole of aluminum hydroxide and 1 mole of (NH 3 ). This reaction was considered as the overall hydrolysis reaction as given below [11,31,32,[35][36][37][38]: ...
... In another comprehensive study, the author claimed the ammonium ion, (NH 4 + ) can only diffuse into the cytoplasmic space through ion channels and the tiny (NH 3 ) molecules can freely penetrate through the membrane [36,[40][41][42][43]. Therefore, based on the previous studies and the results obtained, it can be speculated that the mechanism of antibacterial action is the elution of ammonia (NH 3 ) and ammonium ion (NH 4 + ) during hydrolysis of AlN, as shown in Equations (1)-(3), diffuses into the bacterial cell and damages the DNA as well as causing cell lysis [35][36][37][38][39][40][41][42][43]. ...
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Cellulose acetate (CA) is a synthetic compound that is derived from the acetylation of cellulose. CA is well known as it has been used for many commercial products such as textiles, plastic films, and cigarette filters. In this research, antibacterial CA composites were produced by addition of aluminum nitride (AlN) at different weight percentage, from 0 wt. % to 20 wt. %. The surface characterization was performed using laser microscope, Raman and FTIR spectroscopy. The mechanical and thermal properties of the composite were analyzed. Although the mechanical strength tended to decrease as the concentration of AlN increased and needed to be optimized, the melting temperature (Tm) and glass transition temperature (Tg) showed a shift toward higher values as the AlN concentration increased leading to an improvement in thermal properties. AlN additions in weight percentages >10 wt. % led to appreciable antibacterial properties against S. epidermidis and E. coli bacteria. Antibacterial CA/AlN composites with higher thermal stability have potential applications as alternative materials for plastic packaging in the food industry.
... Each sample was chilled on ice, and 50 µL of the sample was added to the VeroE6/TMPRSS2 cells in each well (in advance, the VeroE6/TMPRSS2 cells had been seeded into 96-well plates at 5 × 10 4 /100 µL/well (N = 4) and cultured for 24 h). After culture for 3 days, the cytopathic effect (CPE) (cell death caused by Omicron variants of SARS-CoV-2) was observed under a phase contrast microscope [17]. ...
Full-text available
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.
... Other new materials appear in the literature that claim attention. Si 3 N 4 particles have been recently reported as effective against virus including SARS-CoV-2 [80]. These non-oxide particles are safe toward mammalian cells. ...
The resistance that microorganisms develop to antibiotics is a worldwide challenge. The antimicrobial agents as disinfectants for surface treatments are widespreadly used to prevent the proliferation of microorganisms, but their use should be repeated over time to ensure a complete microbe-free surface. Surfaces with permanent antimicrobial properties suppose a recent demand in materials science for functional polymeric coatings, metals, treated wood or ceramic glazed tiles. Whereas polymeric coating has been extensively studied, the antimicrobial functionality on ceramic glazed surfaces is not completely achieved. This work reviews glazed ceramic tiles developments in antimicrobial and virucidal surfaces. The main antimicrobial physical or chemical mechanisms have been described as the base to develop active glazed surfaces. The main tests required to evaluate the antimicrobial response in glazed ceramic tiles are also summarized. The high temperature required in the ceramic processing is the key point to achieve a micro/nanostructure that potentiates the antimicrobial and virucidal response of the glazed surfaces. A discussion on recent developments as well as the main routes and challenges to obtain permanent surfaces with antimicrobial and virucidal response is provided.
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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.
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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.
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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.
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Medical-grade masks and N95 respirators containing non-woven fibers are designed to prevent the spread of airborne diseases. While they effectively trap respiratory droplets and aerosols, they cannot lyse entrapped pathogens. Embedded antimicrobial agents such as silver, copper, zinc, iodine, peptides, quaternary ammonium salts, or nanoparticles have been used to overcome this limitation. However, their effectiveness remains debatable because these materials can be toxins, allergens, irritants, and environmental hazards. Recently, silicon nitride (Si 3 N 4 ) was found to be a potent antipathogenic compound, and it may be an ideal agent for masks. In powder or solid form, it is highly effective in inactivating bacteria, fungi, and viruses while leaving mammalian tissue unaffected. The purpose of this study was to serially assess the antiviral efficacy of Si 3 N 4 against SARS-CoV-2 using powders, solids, and embedded nonwoven fabrics. Si 3 N 4 powders and solids were prepared using conventional ceramic processing. The “pad-dry-cure” method was used to embed Si 3 N 4 particles into polypropylene fibers. Fabric testing was subsequently conducted using industrial standards—ISO 18184 for antiviral effectiveness, ASTM F2299 and EN 13274-7 for filtration efficiency, EN 14683 for differential pressure drop, and ISO 18562-2 for particle shedding. A modification of ISO 18562-3 was also employed to detect ammonia release from the fabric. Antiviral effectiveness for Si 3 N 4 powders, solids, and embedded fabrics were 99.99% at ≤ 5 min, ~ 93% in 24 h, and 87% to 92% in 120 min, respectively. Results of the standard mask tests were generally within prescribed safety limits. Further process optimization may lead to commercial Si 3 N 4 -based masks that not only “catch” but also “kill” pathogenic microbes.
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Stability of SARS-CoV-2 in different environmental conditions.
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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.
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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.
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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.
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 (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.
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.
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.