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

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
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© 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 a previous study on the effect of silicon nitride bioceramic powder on SARS-CoV-2, we found that simple contact of the powder with the virus in a dilute aqueous suspension resulted in instantaneous and complete inactivation of the virus. 1 The degree of instantaneous inactivation recorded was similarly observed for other single-stranded RNA (ssRNA) viruses. 2 Subsequently, it was hypothesized that the agent responsible for this effect is ammonia. Conversion into virucidal ammonia from ammonium increasingly occurs with increasing the pH of the aqueous environment. ...
... Such a two-steps antiviral mechanism has been branded as the "catch-and-kill" effect. 1 ...
... but yet suffices to fight viruses and other pathogens, while being retained over several runs of environmental exposure. 1,2,4,13 This behavior is consequence of the enhanced solubility of surface silanols in the alkaline environment developed when nitrogen leaves the solid surface. 96 In summary, the uniqueness of Si 3 N 4 as an antiviral compound is the result of two concurrent and synergic factors: the safety of its Si cation toward eukaryotic cells and the slow and durable kinetics of its hydrolytic reactions. ...
Full-text available
The hydrolytic processes occurring at the surface of silicon nitride (Si3N4) bioceramic have been indicated as a powerful pathway to instantaneous inactivation of SARS-CoV-2 virus. However, the virus inactivation mechanisms promoted by Si3N4 remain yet to be elucidated. In this study, we provide evidence of the instantaneous damage incurred on the SARS-CoV-2 virus upon contact with Si3N4. We also emphasize the safety characteristics of Si3N4 for mammalian cells. Contact between the virions and micrometric Si3N4 particles immediately targeted a variety of viral molecules by inducing post-translational oxidative modifications of S-containing amino acids, nitration of the tyrosine residue in the spike receptor binding domain, and oxidation of RNA purines to form formamidopyrimidine. This structural damage in turn led to a reshuffling of the protein secondary structure. These clear fingerprints of viral structure modifications were linked to inhibition of viral functionality and infectivity. This study validates the notion that Si3N4 bioceramic is a safe and effective antiviral compound; and a primary antiviral candidate to replace the toxic and allergenic compounds presently used in contact with the human body and in long-term environmental sanitation.
... This experiment is difficult to interpret because surface passivation also reduces the dissolution of Cu species. Pezzotti et al. [54] have recently described work where suspensions of both silicon nitrite (Si 3 N 4 ) and aluminum nitride (AlN) were shown to inactivate SARS-CoV-2. They hypothesize a similar method for inactivation via the reactive nitrogen species (RNS), ammonia, generated as the surface of the particles. ...
... Pezzotti et al. [54] measured the activity of silicon nitride (Si 3 N 4 ), copper (Cu), and aluminum nitride The effect of droplet drying on the surface. The concentration of dissolved species increases, and diffusion times get shorter. ...
... The authors reported 100% viral reduction with only 1 min of virus exposure to either Si 3 N 4 , Cu, or AlN. [54] with a viral culture that contained 2 Â 10 4 PFU/mL. They employed Si 3 N 4 concentration from 5 up to 20 w/v%. ...
The COVID-19 pandemic had a major impact on life in 2020 and 2021. One method of transmission occurs when the causative virus, SARS-CoV-2, contaminates solids. Understanding and controlling the interaction with solids is thus potentially important for limiting the spread of the disease. We review work that describes the prevalence of the virus on common objects, the longevity of the virus on solids, and surface coatings that are designed to inactivate the virus. Engineered coatings have already succeeded in producing a large reduction in viral infectivity from surfaces. We also review work describing inactivation on facemasks and clothing, and discuss probable mechanisms of inactivation of the virus at surfaces.
... Such a two-steps virion/surface interaction has been found very effective also in the case of SARS-CoV-2 virions, which could be inactivated up to > 99% within exposure times as short as 1 min. This composite antiviral mechanism was branded as the "catch-and-kill" effect 15 . Regarding possible differences in genomic structures (i.e., the above item (ii)), the heterogeneity observed here among ssRNA viruses toward Si 3 N 4 inactivation is likely also contributed by differences in sequence and length of the genome 61 . ...
... The former mechanism is related to electrostatic attraction exerted by deprotonated surface silanols at the Si 3 N 4 surface, while both the latter two ones arise from molecular infiltrations of eluted NH 3 . The present study is in line with our previously published data [12][13][14][15] , and it specifically confirms our recently published data on the inactivation of SARS-CoV-2 by nitride ceramics 15 . The efficacy of Si 3 N 4 as a solid-state virus inactivator relies on RNS rather than ROS species [12][13][14] . ...
... The former mechanism is related to electrostatic attraction exerted by deprotonated surface silanols at the Si 3 N 4 surface, while both the latter two ones arise from molecular infiltrations of eluted NH 3 . The present study is in line with our previously published data [12][13][14][15] , and it specifically confirms our recently published data on the inactivation of SARS-CoV-2 by nitride ceramics 15 . The efficacy of Si 3 N 4 as a solid-state virus inactivator relies on RNS rather than ROS species [12][13][14] . ...
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Surface inactivation of human microbial pathogens has a long history. The Smith Papyrus (2600 ~ 2200 B.C.) described the use of copper surfaces to sterilize chest wounds and drinking water. Brass and bronze on doorknobs can discourage microbial spread in hospitals, and metal-base surface coatings are used in hygiene-sensitive environments, both as inactivators and modulators of cellular immunity. A limitation of these approaches is that the reactive oxygen radicals (ROS) generated at metal surfaces also damage human cells by oxidizing their proteins and lipids. Silicon nitride (Si 3 N 4 ) is a non-oxide ceramic compound with known surface bacterial resistance. We show here that off-stoichiometric reactions at Si 3 N 4 surfaces are also capable of inactivating different types of single-stranded RNA (ssRNA) viruses independent of whether their structure presents an envelop or not. The antiviral property of Si 3 N 4 derives from a hydrolysis reaction at its surface and the subsequent formation of reactive nitrogen species (RNS) in doses that could be metabolized by mammalian cells but are lethal to pathogens. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) tests of viral RNA and in situ Raman spectroscopy suggested that the products of Si 3 N 4 hydrolysis directly react with viral proteins and RNA. Si 3 N 4 may have a role in controlling human epidemics related to ssRNA mutant viruses.
... 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.
... In aqueous suspension, Si3N4 slowly and continuously elutes sili-4 con and nitrogen through a hydrolytic process. This peculiar chemistry leads to the healing of soft and osseous tissue while eradicating bacteria and viruses [22,23]. The effect is explainable in terms of the pH-dependent kinetics of two nitrogen species, NH3 and NH4 + . ...
... Like DNA damage in bacteria and RNA cleavage in viruses, which we recorded in our previously published studies [22,23,[25][26][27], the endocytotic formation of RNS at the biological interface with Si3N4 is a key factor in candidacidal action. Nevertheless, the metabolic response of C. albicans to Si3N4 shows different patterns and obeys candidacidal mechanisms dissimilar from those active in the case of bacteria and viruses. ...
Previous studies using gram-positive and -negative bacteria demonstrated that hydrolysis of silicon nitride (Si3N4) in aqueous suspensions elutes nitrogen and produces gaseous ammonia while buffering pH. According to immunochemistry assays, fluorescence imaging, and in situ Raman spectroscopy, we demonstrate here that the antipathogenic surface chemistry of Si3N4 can be extended to polymethylmethacrylate (PMMA) by compounding it with a minor fraction (∼8 vol.%) of Si3N4 particles without any tangible loss in bulk properties. The hydrolytic products, which were eluted from partly exposed Si3N4 particles at the composite surface, exhibited fungicidal action against Candida albicans. Using a specific nitrative stress sensing dye and highly resolved fluorescence micrographs, we observed in situ congestion of peroxynitrite (ONOO⁻) radicals in the mitochondria of the Candida cells exposed to the PMMA/Si3N4 composite, while these radicals were absent in the mitochondria of identical cells exposed to monolithic PMMA. These in situ observations suggest that the surface chemistry of Si3N4 mimics the antifungal activity of macrophages, which concurrently produce NO radicals and superoxide anions (O2•⁻) resulting in the formation of candidacidal ONOO⁻. The fungicidal properties of PMMA/Si3N4 composites could be used in dental appliances to inhibit the uncontrolled growth of Candida albicans and ensuing candidiasis while being synergic with chemoprophylaxis. STATEMENT OF SIGNIFICANCE : In a follow-up of previous studies of gram-positive and gram-negative bacteria, we demonstrate here that the antipathogenic surface chemistry of Si3N4 could be extended to polymethylmethacrylate (PMMA) containing a minor fraction (∼8 vol.%) of Si3N4 particles without tangible loss in bulk properties. Hydrolytic products eluted from Si3N4 particles at the composite surface exhibited fungicidal action against Candida albicans. Highly resolved fluorescence microscopy revealed congestion of peroxynitrite (ONOO⁻) radicals in the mitochondria of the Candida cells exposed to the PMMA/Si3N4 composite, while radicals were absent in the mitochondria of identical cells exposed to monolithic PMMA. The fungicidal properties of PMMA/Si3N4 composites could be used in dental appliances to inhibit uncontrolled growth of Candida albicans and ensuing candidiasis in synergy with chemoprophylaxis.
... 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.
... Chilled on ice, 100 µL of each sample was added to the VeroE6/TMPRSS2 cells that had been seeded into 96-well-plates at 5 × 10 4 /100 µL/well a day before. After culture for 4 days, cells were washed, fixed, and stained with crystal violet solution to estimate CPE as described [27]. ...
Full-text available
Potential effects of tea and its constituents on SARS-CoV-2 infection were assessed in vitro. Infectivity of SARS-CoV-2 was decreased to 1/100 to undetectable levels after a treatment with black tea, green tea, roasted green tea, or oolong tea for 1 min. An addition of (−) epigallocatechin gallate (EGCG) significantly inactivated SARS-CoV-2, while the same concentration of theasinensin A (TSA) and galloylated theaflavins including theaflavin 3,3′-di-O-gallate (TFDG) had more remarkable anti-viral activities. EGCG, TSA, and TFDG at 1 mM, 40 µM, and 60 µM, respectively, which are comparable to the concentrations of these compounds in tea beverages, significantly reduced infectivity of the virus, viral RNA replication in cells, and secondary virus production from the cells. EGCG, TSA, and TFDG significantly inhibited interaction between recombinant ACE2 and RBD of S protein. These results suggest potential usefulness of tea in prevention of person-to-person transmission of the novel coronavirus.
... Chilled on ice, 100 µL of each sample was added to the VeroE6/TMPRSS2 cells that had been seeded into 96-well-plates at 5 × 10 4 /100 µL/well a day before. After culture for 4 days, cells were washed, fixed and stained with crystal violet solution to estimate CPE as described [14]. ...
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Saliva plays major roles in the human-to-human transmission of SARS-CoV-2. If the virus in saliva in SARS-CoV-2-infected individuals can be rapidly and efficiently inactivated by a beverage, the ingestion of the beverage may attenuate the spread of virus infection within a population. Recently, we reported that SARS-CoV-2 was significantly inactivated by treatment with black tea, green tea, roasted green tea and oolong tea, as well as their constituents, (-) epigallocatechin gallate (EGCG), theasinensin A (TSA), and galloylated theaflavins. However, it remains unclear to what extent tea inactivates the virus present in saliva, because saliva contains various proteins, nitrogenous products, electrolytes, and so on, which could influence the antivirus effect of tea. Here, we assessed whether tea inactivated the SARS-CoV-2 which was added in human saliva. A virus was added in healthy human saliva in vitro, and after treatment with black tea or green tea, the infectivity of the virus was evaluated by TCID50 assays. The virus titer fell below the detectable level or less than 1/100 after treatment with black tea or green tea for 10 s. The black tea-treated virus less remarkably replicated in cells compared with the untreated virus. These findings suggest the possibility that the ingestion of tea may inactivate SARS-CoV-2 in saliva in infected individuals, although clinical studies are required to determine the intensity and duration of the anti-viral effect of tea in saliva in humans.
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The Raman spectrum of living cells and microorganisms contains highly specific fingerprint-like signatures, useful in unequivocally identifying different species and interpreting physiological and metabolic responses to environmental stressors. In situ Raman imaging with dedicated highly sensitive instruments can translate selected spectroscopic fingerprints into vivid snapshots of molecular species or specific physiological reactions. Time-lapse experiments, crucial in characterizing growth-dependent phenomena and metabolic response to drugs or substrates, are possible because Raman imaging is life compatible. This review covers miscellaneous examples of Raman analyses and imaging of eukaryotic cells, bacteria, and viruses. Fundamental microbiological analyses covered here include (i) identification of different species of cells, bacteria, and viruses; (ii) characterization of the metabolic responses of cells and bacteria to different substrates; (iii) time-lapse analyses of cell metabolic reactions upon viral inoculation; (iv) chemical imaging of axon sprouting in neuronal cells; and (v) visualization of the myelinating activity of living Schwann cells in coculture with neuronal cells. The spectroscopic findings displayed here, which are based on a machine learning approach applied to Raman analysis and imaging, demonstrate the invaluable potential for Raman spectroscopy in biophysics research. © 2021 The Author. Journal of Raman Spectroscopy published by John Wiley & Sons Ltd.
Infectious diseases caused by viruses are a global health concern and have become prominent in light of the recent COVID‐19 pandemic. Considering the limitations of drugs and prophylactic methods used in current medicine, antiviral materials are a useful strategy in preventing the spread of viruses and enhancing treatment efficiency. Thus, this review highlights the state‐of‐the‐art antiviral materials, describes the scientific landscape of the primary antiviral materials used based on bibliometric analysis, presents their mechanisms of action, and discusses their clinical applications. The mechanisms of action underlying the broad‐spectrum antiviral properties of metals, ceramics, polymers, and composites are also discussed. Polyanions, polycations, oxides, and metal‐based materials, from bulk to nanoparticles, have good potential in antiviral applications that may help prepare the world for future viral breakouts. Recent progress in materials designed against viruses is reviewed here with respect to the main antiviral mechanisms and applications of metals, polymers, ceramics, and composites. Antiviral materials discussed in the literature from bulk to nanoparticles are presented, guided by bibliometric analysis. Metal‐based surfaces and nanoparticles, oxides, carbon nanostructures, polycations, and polyanions are some promising materials explored with a broad‐spectrum of antiviral activity.
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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.
Stability of SARS‐CoV‐2 in different environmental conditions
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