WO2022005550A1 - Systems and methods for rapid inactivation of sars-cov-2 by silicon nitride and aluminum nitride - Google Patents
Systems and methods for rapid inactivation of sars-cov-2 by silicon nitride and aluminum nitride Download PDFInfo
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- WO2022005550A1 WO2022005550A1 PCT/US2021/027263 US2021027263W WO2022005550A1 WO 2022005550 A1 WO2022005550 A1 WO 2022005550A1 US 2021027263 W US2021027263 W US 2021027263W WO 2022005550 A1 WO2022005550 A1 WO 2022005550A1
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Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
- A01N59/06—Aluminium; Calcium; Magnesium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A41—WEARING APPAREL
- A41D—OUTERWEAR; PROTECTIVE GARMENTS; ACCESSORIES
- A41D31/00—Materials specially adapted for outerwear
- A41D31/04—Materials specially adapted for outerwear characterised by special function or use
- A41D31/30—Antimicrobial, e.g. antibacterial
Definitions
- the present disclosure generally relates to rapid inactivation of a virus, and in particular to systems and methods for rapid capture and inactivation of SARS-CoV-2 by silicon nitride and/or aluminum nitride.
- SARS-CoV-2 The novel coronavirus, SARS-CoV-2, has led to a worldwide pandemic and raised interest in the surface-mediated transmission of viral diseases. Respiratory aerosols and droplets, and contaminated surfaces facilitate viral spread from person to person leading to recommendations of social distancing, wearing of masks, hand-washing, and regular surface disinfection. Data suggest that the SARS- CoV-2 virus can remain viable on copper, plastic, steel, and cardboard surfaces for 4-72 hours after contact, and up to 7-days on surgical masks. Viral persistence on these and other materials presents a risk for the social and nosocomial propagation of COVID-19, the disease caused by SARS-CoV-2.
- the object may comprise silicon nitride or aluminum nitride, wherein the silicon nitride or aluminum nitride successively binds (i.e. captures) and then inactivates the virus.
- the silicon nitride or the aluminum nitride may be present on the surface of the object as a coating or may be incorporated into the object.
- the silicon nitride is present at a concentration from about 1 wt.% to about 30 wt.%.
- the object may contact the virus for at least one minute or for at least 30 minutes.
- the virus may be at least 75% inactivated after contact with the object for at least 1 minute.
- the object may comprise paper, cardboard, polymers, fabric, plastic, ceramic, stainless steel, and/or metal.
- the object is a protective gown, a body cover, a head cover, a shoe cover, a face mask, a face shield, an eye protector, gloves, a surgical gown, a surgical drape, or a cubicle curtain.
- the object is a face mask filter, a respirator filter, an air filtration filter, or an air ventilation filter.
- the object is a knob, a handle, a railing, a bed frame, a bed tray, a table, a chair, an equipment rack, or a cart.
- the object may be composition such as a slurry, suspension, gel, paint, or toothpaste.
- the article comprises silicon nitride or aluminum nitride.
- the silicon nitride or the aluminum nitride may be incorporated into the article or may be coated onto the surface of the article.
- the silicon nitride or aluminum nitride may be present at a concentration of about 1 wt.% to about 30 wt.%.
- the article may be a body cover, a head cover, a shoe cover, a face mask, a face and eye protector, or gloves.
- the article is operable to bind/capture and then inactivate the SARS-CoV-2 virus upon contact with the virus.
- FIGS. 2A-2D are graphical representations that show viral RNA that has underwent severe degradation after exposure to copper or nitride particles.
- FIG. 2A and FIG. 2B virus suspensions were exposed to Cu, AIN and S13N4 powders for 1 minute, and viral RNA in supernatants and on particles were evaluated using viral N gene “set 1” and “set 2” primers, respectively. Data collected on supernatants and pellet samples are given in comparison with the amount of viral N gene RNA in suspension that was left untreated.
- FIG. 2C and FIG. 2D results of RT-PCR tests after 10-minute exposure of supernatants to Cu, AIN and S13N4 powders for viral N gene “set 1” and “set 2” primers are shown, respectively.
- FIGS. 3A-3E are images showing S13N4 suppressed virus infection without affecting cell viability in which Cu killed the cells.
- VeroE6/TMPRSS2 cells were inoculated with (FIG. 3A) unexposed virions, and virions 10-minute UTE- exposed to Si 3 N (FIG. 3B), AIN (FIG. 3C), and Cu (FIG. 3D).
- FIGS. 5A-5G are graphical representations of Raman spectra for: (a) uninfected cells (FIG. 5A) (i.e. , unexposed to virions), and cells infected with SARS-CoV-2 virions exposed for 10 minutes to (b) S13N4 (FIG. 5B), (c) AIN (FIG.
- FIG. 5C Raman spectrum of cells infected by unexposed virions (negative control).
- FIG. 5F a plot of the average intensity of the two tryptophan T 1 and T2 bands (at 756 and 875 cm-1 , respectively) as a function of fraction of infected cells by virions unexposed and exposed for 10-min to different particles (cf. labels); in the inset, the structure of N’-formylkynurenine, an intermediate in the catabolism of tryptophan upon enzymatic IDO reaction.
- FIG. 5G a graphical representation shows three possible conformations of tyrosine-based peptides that can justify the disappearance of ring vibrations in tyrosine (Ty2 band) upon chelation of Cu(ll) ions.
- FIG. 6 is a schematic model illustrating a chemical and electrical charge similarity between the protonated amine groups, Si-NH3 + , at the surface of S13N4 and the N-terminal of lysine, C-NH3 + in cells (left panel); and, the interaction of SARS-CoV-2 viruses with the charged molecular species at the surface of S13N4 (specifically, at protonated amines charging plus) and the eluted species NH3/NH4 + (central panel).
- the eluted N leaves 3+ charged vacancies on the solid surface (violet-colored sites), which stem together with negatively charged silanols.
- silicon nitride includes a-Si3N4, b- SisN4, SiYAION, b-SiYAION, SiYON, SiAION, or combinations thereof.
- inactivate refers to viral inactivation in which the virus is stopped from contaminating the product or subject either by removing virus completely or rendering them non-infectious.
- object refers to materials, compositions, devices, surface coatings, and/or composites.
- the apparatus may include various medical devices or equipment, examination tables, clothing, filters, personal protective equipment such as masks and gloves, catheters, endoscopic instruments, commonly-touched surfaces where viral persistence may encourage the spread of disease, and the like.
- the apparatus may be metallic, polymeric, and/or ceramic (ex. silicon nitride and/or other ceramic materials).
- contact means in physical contact or within close enough proximity to a composition or apparatus to be affected by the composition or apparatus.
- PPE personal protective equipment
- body covers head covers, shoe covers, face masks, eye protectors, face and eye protectors, and gloves.
- a method for inactivating the SARS-CoV-2 virus by contacting the virus with an object or composition comprising silicon nitride and/or aluminum nitride.
- the silicon nitride and/or aluminum nitride successively binds (i.e. captures) and then inactivates the virus (e.g. “catch and kill”).
- Silicon nitride possesses a unique surface chemistry which is biocompatible and provides a number of biomedical applications including 1 ) concurrent osteogenesis, osteoinduction, osteoconduction, and bacteriostasis, such as in spinal and dental implants; 2) killing of both gram-positive and gram-negative bacteria according to different mechanisms; 3) inactivation of human and animal viruses, bacteria, and fungi; and 4) polymer- or metal-matrix composites, natural or manmade fibers, polymers, or metals containing silicon nitride powder retain key silicon nitride bone restorative, bacteriostatic, antiviral, and antifungal properties.
- Silicon nitride is a non-oxide ceramic compound that has been used in many industries since the 1950s.
- Clinical data for S13N4 implants compare favorably with other spine biomaterials, such as allograft, titanium, and polyetheretherketone.
- S13N4 implants have a lower incidence of bacterial infection (i.e., less than 0.006%) when compared to other implant materials (2.7% to 18%).
- S13N4 This property reflects the complex surface biochemistry of S13N4 that elutes minute amounts of nitrogen, which is converted to ammonia, ammonium, and other reactive nitrogen species (RNS) that inhibit bacteria.
- RNS reactive nitrogen species
- Silicon nitride may be antipathogenic due to release of nitrogen containing species when in contact with an aqueous medium, or biologic fluids and tissues.
- the surface chemistry of silicon nitride may be shown as follows:
- the present disclosure compares the effects of exposing SARS- CoV-2 to aqueous suspensions of S13N4 and aluminum nitride (AIN) particles and two controls, (i.e. , a suspension of copper (Cu) particles (positive control) and a sham suspension of SARS-CoV-2 virions without any antiviral agent (negative control)).
- Copper (Cu) was chosen as a positive control because of its well-known ability to inactivate a variety of microbes, including viruses.
- Aluminum nitride was included in the testing because, like S13N4, it is a nitrogen-based compound whose surface hydrolysis in aqueous solution leads to the elution of nitrogen, with an attendant increase in pH. Since comparable antiviral and antibacterial phenomena are believed to be operative for all nitride-based compounds, AIN was used to provide additional insight into the antipathogenic mechanisms of nitrogen-containing inorganic materials.
- compounds capable of endogenous nitrogen- release can inactivate the SARS-CoV-2 virus at least as effectively as Cu.
- multiple antiviral mechanisms may be operative, such as RNA fragmentation, and in the case of Cu and AIN, direct metal ion toxicity; but while Cu and AIN supernatants demonstrated cellular lysis, S13N4 may provoke no metabolic alterations.
- the Raman spectrum of VeroE6 cells exposed to the S13N4 viral supernatant was like that of the uninfected sham.
- the antiviral effect may be related to the electrical attraction (including “competitive binding” to an envelope glycoprotein hemagglutinin in the case of influenza virus) and viral RNA fragmentation by reactive nitrogen species (RNS). These phenomena are due to the slow and controlled elution of nitrogen from Si3N4’s surface which forms ammonia (NH3) and ammonium (NH4 + ) moieties coupled with the release of free electrons and negatively charged silanols in aqueous solution.
- electrical attraction including “competitive binding” to an envelope glycoprotein hemagglutinin in the case of influenza virus
- RNS reactive nitrogen species
- an object, article, or composition comprising silicon nitride or aluminum nitride may be operable to successively bind a virus (e.g. SARS-Cov-2) and then inactivate the virus.
- a virus e.g. SARS-Cov-2
- the antiviral effectiveness of S13N4 may be comparable to Cu. While Cu is an essential trace element for human health and an electron donor/acceptor for several key enzymes by altering redox states between Cu + and Cu 2+ , these properties can also cause cellular damage. Its use as an antiviral agent is limited by allergic dermatitis, hypersensitivity, and multi-organ dysfunction. In contrast, the safety of S13N4 as a permanently-implanted material during spine fusion surgery is well established by experimental and clinical data. Therefore, an object, article, or composition comprising silicon nitride may be as effective at inactivating a virus as Cu without the negative effects of Cu.
- S13N4 is well-known for its capabilities as an industrial material.
- S13N4 prosthetic hip bearings and spinal fusion implants were initially developed because of the superior strength and toughness of S13N4. Later studies showed other properties of S13N4 that are favored in designing orthopaedic implants, such as enhanced osteoconductivity, bacteriostasis, improved radiolucency, lack of implant subsidence, and wear resistance. Therefore, SbN s surface chemistry, topography, and hydrophilicity contribute to a dual effect (i.e. , upregulation of osteogenic activity to promote spinal fusion while simultaneously preventing bacterial adhesion and biofilm formation). In addition to its proven record as a bioimplant, an advantage of S13N4 is its versatility of manufacture.
- Sintered powders of S13N4 have been incorporated into other materials, such as polymers, other ceramics, bioglass, and metals, to create composite structures that maintain the index osteogenic and antibacterial properties of monolithic S13N4.
- Three-dimensional additive deposition of S13N4 may enable the manufacture of protective surfaces in health care that reduce fomite-mediated transmission of microbial disease.
- Incorporation of S13N4 particles into the fabric of personal protective equipment, such as face masks, protective gowns, and surgical drapes could contribute to health workers as well as patient safety.
- S13N4 inactivates the SARS-CoV-2 virus in a matter of minutes following exposure.
- the mechanism of action may be shared with other nitrogen-based compounds that express trace amounts of surface disinfectants, such as aluminum nitride.
- the object used to bind and inactivate the SARS-CoV-2 virus is a device or apparatus that may include a silicon nitride and/or aluminum nitride composition on at least a portion of a surface of the object.
- the silicon nitride or aluminum nitride coating may be applied to the surface of the object as a powder.
- the silicon nitride or aluminum nitride powder may be filled, embedded, or impregnated in at least a portion of the object.
- the powder may have particles in the micron, submicron or nanometer size range.
- the average particle size may range from about 100 nm to about 5 pm, from about 300 nm to about 1.5 pm, or from about 0.6 pm to about 1.0 pm.
- the silicon nitride or aluminum nitride may be incorporated into the device.
- an object may incorporate a silicon nitride and/or aluminum nitride powder within the body of the object.
- the device may be made of silicon nitride.
- the object may be made of aluminum nitride.
- the object can comprise a slurry or suspension of aluminum nitride or silicon nitride particles.
- the object may further comprise other materials including, but not limited to, paper, cardboard, fabric, plastic, ceramic, polymers, stainless steel, metal, or a combination thereof.
- Some non-limiting examples of the object may include surgical gowns, surgical drapes, shoe covers, cubicle curtains, tubing, clothing, gloves, eye protectors, masks including surgical masks and face shields, PPE, tables such as hospital exam and surgical tables, chairs, bed frames, bed trays, desks, fixtures, cabinets, equipment racks, carts, handles, knobs, railings, toys, water filters, and air filters such as face mask filters, respirator filters, air filtration filters, and air ventilation filters, or air conditioner filters.
- the filters may be within filtration devices of anesthesia machines, ventilators, or CPAP machines such that an antimicrobial surface layer in the filter can trap pulmonary pathogens, as air moves in and out of infected lungs.
- the object may be a medical device or apparatus.
- medical devices or apparatuses include orthopedic implants, spinal implants, pedicle screws, dental implants, in-dwelling catheters, endotracheal tubes, colonoscopy scopes, and other similar devices.
- the object may be a composition incorporating silicon nitride or aluminum nitride powder therein including, but not limited to slurries, suspensions, gels, sprays, paint, or toothpaste.
- silicon nitride or aluminum nitride to a slurry, such as paint, that is then applied to a surface may provide an antibacterial, antifungal, and antiviral surface.
- silicon nitride or aluminum nitride may be mixed with water along with any appropriate dispersants and slurry stabilization agents, and thereafter applied by spraying the slurry onto various surfaces.
- An example dispersant is Dolapix A88.
- the silicon nitride or aluminum nitride coating may be present on the surface of the object in a concentration of about 1 wt.% to about 100 wt.%.
- the silicon nitride and/or aluminum nitride may be coated onto or layered into the object.
- the coating may include about 1 wt.%, 2 wt.%, 5 wt.%, 7.5 wt.%, 8.3 wt.%, 10 wt.%, 15 wt.%, 16.7 wt.%, 20 wt.%, 25 wt.%, or about 30 wt.% silicon nitride powder or aluminum nitride powder.
- the coating may include about 10 wt.% to about 20 wt.% silicon nitride or aluminum nitride. In at least one example, the coating includes about 15 wt.% silicon nitride or aluminum nitride. In some embodiments, silicon nitride or aluminum nitride may be embedded in (as a filler) or on the surface of the object in a concentration of about 1 wt.% to about 100 wt.%.
- the object may include about 1 wt.%, 2 wt.%, 5 wt.%, 7.5 wt.%, 8.3 wt.%, 10 wt.%, 15 wt.%, 16.7 wt.%, 20 wt.%, 25 wt.%, 30 wt.%, 33.3 wt.%, 35 wt.%, 40 wt.%, 50 wt.%, 60 wt.%, 70 wt. %, 80 wt.%,
- the silicon nitride or aluminum nitride may be on the surface of the object at a concentration of about 10 wt.% to about 20 wt.%. In at least one example, the silicon nitride or aluminum nitride may be on the surface of the object at a concentration of about 15 wt.%. In some aspects, the concentration of silicon nitride or aluminum nitride may depend on the substrate material of the object, such as paper, cardboard, fabric, plastic, ceramic, polymers, stainless steel, and/or metal.
- the substrate material of the object may be a polymer and the polymer may have a practical limit (i.e. percolation limit) on the amount of silicon nitride and/or aluminum nitride that may be incorporated into the object.
- a practical limit i.e. percolation limit
- the object may be a monolithic component consisting of the silicon nitride or aluminum nitride.
- Such an object may be fully dense possessing no internal porosity, or it may be porous, having a porosity that ranges from about 1% to about 80%.
- the monolithic object may be used as a medical device or may be used in an apparatus in which the inactivation of a virus may be desired.
- the object may contact the SARS-CoV-2 virus for a limited period of time.
- the object may be in contact with the SARS-CoV-2 virus for about 1 min to about 2 hours in order to inactivate the virus.
- the object may contact the SARS-CoV-2 virus for at least 30 seconds, at least 1 minute, at least 5 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, at least 5 hours, or at least 1 day.
- the object may be permanently implanted in the patient.
- the object may be worn externally by a user.
- the object may be permanently implanted in the patient.
- the object may be a high contact surface.
- the object may be in continuous or sustained contact with a body fluid of a patient.
- the body fluid may be blood or gas (e.g., inhalation or exhalation gas).
- the virus is at least 70% inactivated, at least 75% inactivated, at least 80% inactivated, at least 85% inactivated, at least 90% inactivated, at least 95% inactivated, or at least 99% inactivated after contact with the object for at least 1 minute, at least 5 minutes, or at least 30 minutes. In at least one example, the virus is at least 85% inactivated after contact with object for at least 1 minute. In another example, the virus is at least 99% inactivated after contact with the object for at least 30 minutes. In yet another example, the virus is at least 99% inactivated after contact with the object for at least 1 minute.
- the article may comprise silicon nitride or aluminum nitride incorporated into the article or the silicon nitride or aluminum nitride may be coated onto the surface of the article.
- the silicon nitride or aluminum nitride coating may be present on the surface of the article in a concentration of about 1 wt.% to about 100 wt.%.
- the coating may include about 1 wt.%, 2 wt.%, 5 wt.%, 7.5 wt.%, 8.3 wt.%, 10 wt.%, 15 wt.%, 16.7 wt.%, 20 wt.%, 25 wt.%, or about 30 wt.% silicon nitride powder or aluminum nitride powder.
- the coating may include about 10 wt.% to about 20 wt.% silicon nitride or aluminum nitride. In at least one example, the coating includes about 15 wt.% silicon nitride or aluminum nitride. In some embodiments, silicon nitride or aluminum nitride may be embedded in (as a filler) or on the surface of the article in a concentration of about 1 wt.% to about 100 wt.%.
- the object may include about 1 wt.%, 2 wt.%, 5 wt.%, 7.5 wt.%, 8.3 wt.%, 10 wt.%, 15 wt.%, 16.7 wt.%, 20 wt.%, 25 wt.%, 30 wt.%, 33.3 wt.%, 35 wt.%, 40 wt.%, 50 wt.%, 60 wt.%, 70 wt. %, 80 wt.%, 90 wt.%, to 100 wt.% silicon nitride or aluminum nitride.
- the silicon nitride or aluminum nitride may be on the surface of the article at a concentration of about 10 wt.% to about 20 wt.%. In at least one example, the silicon nitride or aluminum nitride may be on the surface of the article at a concentration of about 15 wt.%. In some aspects, the concentration of silicon nitride or aluminum nitride may depend on the substrate material of the object.
- the article is PPE.
- the article is a body cover, a head cover, a shoe cover, a face mask, a face and eye protector, or gloves.
- the article is operable to inactivate a SARS- CoV-2 virus when the article contacts the virus. Examples
- S13N4, Cu, and AIN powders were acquired from commercial sources.
- S13N4 powder (nominal composition of 90 wt.% S13N4, 6 wt.% Y2O3, and 4 wt.% AI2O3) was prepared by aqueous mixing and spray-drying of the inorganic constituents, followed by sintering of the spray-dried granules ( ⁇ 1700°C for ⁇ 3 h), hot-isostatic pressing ( ⁇ 1600°C, 2 h, 140 MPa in N2), aqueous-based comminution, and freeze-drying.
- the resulting powder had an average particle size of 0.8 ⁇ 1.0 pm.
- As-received Cu powder (USP grade 99.5% purity) granules were comminuted to achieve a particle size comparable to the S13N4.
- AIN powder had an average particle size of 1.2 ⁇ 0.6 pm as-received, which was comparable to S13N4.
- VeroE6/TMPRSS2 mammalian cells were used in the viral assays. Cells were grown in Dulbecco’s modified Eagle’s minimum essential medium (DMEM) supplemented with G418 disulfate (1 mg/ml), penicillin (100 units/mL), streptomycin (100 pg/mL), 5% fetal bovine serum, and maintained at 37°C in a 5% C02 / 95% in a humidified atmosphere. The SARS-CoV-2 viral stock was propagated using VeroE6/TMPRSS2 cells at 37°C for 2 days. Viral titers were assayed by a median tissue culture infectious dose (TCID50).
- TCID50 median tissue culture infectious dose
- Vero E6/TMPRSS2 cells on cover glass were inoculated with 200 mI_ of virus supernatant. After viral adsorption at 37°C for 1 hour, the cells were incubated with the maintenance medium in a C02 incubator for 7 hour. For the detection of infected cells, these cells were washed with TBS (20 mM Tris-HCI pH 7.5, 150 mM NaCI) and fixed with 4% PFAfor 10 min at room temperature (RT) followed by membrane permeabilization with 0.1% Triton X in TBS for 5 minutes at RT.
- TBS 20 mM Tris-HCI pH 7.5, 150 mM NaCI
- Rabbit anti-SARS Coronavirus envelope
- Vero E6/TMPRSS2 cells were infected with 200 mI_ of each virus suspension onto glass sites. After viral adsorption at 37 °C for 1 hours, the infected cells were incubated with the maintenance medium in a CO2 incubator for 4 hours and fixed with 4% paraformaldehyde for 10 minutes at RT. After washing with distilled water twice, infected cells were air-dried and in situ analyzed using a Raman microprobe spectrometer. Raman spectra were collected using a highly sensitive spectroscope with a 20x optical lens. It operated in microscopic measurement mode with confocal imaging in two dimensions.
- a holographic notch filter within the optical circuit was used to efficiently achieve a spectral resolution of 1.5 cm-1 via a 532 nm excitation source operating at 10 mW.
- Raman emissions were monitored using a single monochromator connected to an air-cooled charge-coupled device (CCD) detector 1024 c 256 pixels). The acquisition time was fixed at 10 seconds. Thirty spectra were collected and averaged for each analysis time-point. Raman spectra were deconvoluted into Gaussian-Lorentzian sub-bands using commercially available software.
- TCID50 assay results for the 15 wt.% S13N4, Cu, and AIN powders are shown in FIGS. 1A-1D.
- Inactivation times of 1 and 10 minutes are shown in FIGS. 1A and 1B as well as FIGS. 1C and 1D, respectively.
- Relative to the negative control all three powders were effective in inactivating SARS-CoV-2 virions (>99%) for the two exposure times.
- RNA was fragmented from exposure to both the supernatants and powders RT-PCR tests were conducted on the N gene sets of the virus’ RNA. The results are shown in Fig. 2A and 2B as well as FIGS. 2C and 2D for 1- and 10-minute exposures, respectively. Again, in comparison to the negative control at 1 minute of exposure to the supernatants, almost complete fragmentation of the RNA was observed for Cu while significant damage was caused by AIN and to a lesser extent by S13N4. After 10-minute exposure to the supernatants, substantial cleavage of the RNA was seen for all three materials. While Cu still showed the most fragmentation, S13N4 demonstrated similar effectiveness, and AIN was essentially identical to the 1 -minute exposure condition.
- Viral RNA was virtually undetectable for all three materials based on extracted RNA from the pelleted powders at 1-minute of exposure (of., FIGS. 2A and 2B). This result suggests that the decrease of viral RNA in the supernatant was not because of adherence of the RNA to the powders, but rather due to direct degradation.
- FIGS. 3A-3D show fluorescence micrographs representative of the VeroE6/TMPRSS2 cell populations that were inoculated with supernatants of (a) unexposed virions (i.e. , negative control) and 10-minute-exposed virions of (b) S13N4, (c) AIN, and (d) Cu.
- FIG. 1 shows that unexposed virions (i.e. , negative control) and 10-minute-exposed virions of (b) S13N4, (c) AIN, and (d) Cu.
- FIG. 3E shows cells that were not inoculated with the virus (labeled as “sham-infected” cells.
- the red-colored spots in the negative control (FIG. 3A) demonstrated that the virions had entered and hijacked the Vero6E cells’ metabolism. This contrasts with the sham-infected cells (FIG. 3E) which showed normal metabolic function.
- FIGS. 5A-5G show Raman spectra in the frequency range 700-900 cm-1 for (a) uninfected VeroE6/TMPRSS2 cells, and cells inoculated with supernatants containing virions exposed for 10-minutes to (b) S13N4, (c) AIN, (d) Cu (positive control), and (e) no antiviral compounds (negative control).
- Tryptophan plays a vital role in protein synthesis and the generation of molecules for various immunological functions. Its stereoisomers serve to anchor proteins within the cell membrane and its catabolites possess immunosuppressive functions. The catabolism of tryptophan is triggered by a viral infection. This occurs via the enzymatic activity of indoleamine-2, 3-dioxygenase (IDO) which protects the host cells from an over-reactive immune response.
- IDO indoleamine-2, 3-dioxygenase
- IDO reduces tryptophan to kynurenine and then to N’-formyl-kynurenine.
- An increase in IDO activity depletes tryptophan. Consequently, the intensity of the tryptophan bands (T1 and T2) is an indicator of these biochemical changes.
- the data presented in FIG. 5F show an exponential decline in the combined tryptophan bands that correlates with the fraction of infected cells. (The chemical structure of N’-formyl- kynurenine is given in the inset for clarity.)
- the anomaly for copper provides further evidence of its toxicity.
- the VeroE6 cells consumed tryptophan to reduce Cu 2+ and stabilize it as Cu + .
- the Raman signals due to ring-stretching vibrations of adenine, cytosine, guanine, and thymine were found at 725, 795, 680, and 748 cm-1 , and are labeled as A, Cy1 , G, and Th, respectively, in FIGS. 5A-5E). These bands were preserved after virus exposure. However, there was an anomaly for lines representative of tyrosine at 642 and 832 cm-1 labeled as Ty1 and Ty2, respectively for cells infected with Cu-exposed virions. The ring-breathing band Ty2 of tyrosine was very weak compared to the other samples (of. FIG. 5D with FIG. 5B).
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Abstract
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Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
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EP21832601.5A EP4171225A1 (en) | 2020-06-29 | 2021-04-14 | Systems and methods for rapid inactivation of sars-cov-2 by silicon nitride and aluminum nitride |
JP2022579906A JP2023532452A (en) | 2020-06-29 | 2021-04-14 | Systems and methods for rapid deactivation of SARS-COV-2 by silicon nitride and aluminum nitride |
MX2022016056A MX2022016056A (en) | 2020-06-29 | 2021-04-14 | Systems and methods for rapid inactivation of sars-cov-2 by silicon nitride and aluminum nitride. |
KR1020227044413A KR20230029646A (en) | 2020-06-29 | 2021-04-14 | Systems and methods for rapid inactivation of SARS-COV-2 by silicon nitride and aluminum nitride |
CN202180046585.9A CN115996635A (en) | 2020-06-29 | 2021-04-14 | System and method for rapid inactivation of SARS-COV-2 by silicon nitride and aluminum nitride |
AU2021301031A AU2021301031A1 (en) | 2020-06-29 | 2021-04-14 | Systems and methods for rapid inactivation of SARS-CoV-2 by silicon nitride and aluminum nitride |
CA3182834A CA3182834A1 (en) | 2020-06-29 | 2021-04-14 | Systems and methods for rapid inactivation of sars-cov-2 by silicon nitride and aluminum nitride |
BR112022026025A BR112022026025A2 (en) | 2020-06-29 | 2021-04-14 | SYSTEMS AND METHODS FOR RAPID INACTIVATION OF SARS-COV-2 BY SILICON NITRIDE AND ALUMINUM NITRIDE |
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US202063045355P | 2020-06-29 | 2020-06-29 | |
US63/045,355 | 2020-06-29 |
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WO2022005550A1 true WO2022005550A1 (en) | 2022-01-06 |
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PCT/US2021/027263 WO2022005550A1 (en) | 2020-06-29 | 2021-04-14 | Systems and methods for rapid inactivation of sars-cov-2 by silicon nitride and aluminum nitride |
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Country | Link |
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EP (1) | EP4171225A1 (en) |
JP (1) | JP2023532452A (en) |
KR (1) | KR20230029646A (en) |
CN (1) | CN115996635A (en) |
AU (1) | AU2021301031A1 (en) |
BR (1) | BR112022026025A2 (en) |
CA (1) | CA3182834A1 (en) |
MX (1) | MX2022016056A (en) |
WO (1) | WO2022005550A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022125797A1 (en) * | 2020-12-09 | 2022-06-16 | Sintx Technologies, Inc. | Nitride based antipathogenic compositions and devices and methods of use thereof |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20200079651A1 (en) * | 2018-09-06 | 2020-03-12 | Sintx Technologies, Inc. | Antipathogenic devices and methods thereof |
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2021
- 2021-04-14 EP EP21832601.5A patent/EP4171225A1/en active Pending
- 2021-04-14 CN CN202180046585.9A patent/CN115996635A/en active Pending
- 2021-04-14 WO PCT/US2021/027263 patent/WO2022005550A1/en unknown
- 2021-04-14 CA CA3182834A patent/CA3182834A1/en active Pending
- 2021-04-14 MX MX2022016056A patent/MX2022016056A/en unknown
- 2021-04-14 JP JP2022579906A patent/JP2023532452A/en active Pending
- 2021-04-14 BR BR112022026025A patent/BR112022026025A2/en not_active Application Discontinuation
- 2021-04-14 AU AU2021301031A patent/AU2021301031A1/en active Pending
- 2021-04-14 KR KR1020227044413A patent/KR20230029646A/en unknown
Patent Citations (1)
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US20200079651A1 (en) * | 2018-09-06 | 2020-03-12 | Sintx Technologies, Inc. | Antipathogenic devices and methods thereof |
Non-Patent Citations (1)
Title |
---|
PEZZOTTI GIUSEPPE, OHGITANI ERIKO, SHIN-YA MASAHARU, ADACHI TETSUYA, MARIN ELIA, BOSCHETTO FRANCESCO, ZHU WENLIANG, MAZDA OSAM: "Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride", BIORXIV, 20 June 2020 (2020-06-20), XP055895687, Retrieved from the Internet <URL:https://www.biorxiv.org/content/10.1101/2020.06.19.159970v1.full.pdf> DOI: 10.1101/2020.06.19.159970 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022125797A1 (en) * | 2020-12-09 | 2022-06-16 | Sintx Technologies, Inc. | Nitride based antipathogenic compositions and devices and methods of use thereof |
Also Published As
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BR112022026025A2 (en) | 2023-01-17 |
MX2022016056A (en) | 2023-02-02 |
CA3182834A1 (en) | 2022-01-06 |
CN115996635A (en) | 2023-04-21 |
JP2023532452A (en) | 2023-07-28 |
KR20230029646A (en) | 2023-03-03 |
EP4171225A1 (en) | 2023-05-03 |
AU2021301031A1 (en) | 2023-02-02 |
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