Dataset Information

Efficacy of Grignard Pure to Inactivate Airborne Phage MS2, a Common SARS-CoV-2 Surrogate.

ABSTRACT: Grignard Pure (GP) is a unique and proprietary blend of triethylene glycol (TEG) and inert ingredients designed for continuous antimicrobial treatment of air. TEG has been designated as a ″Safer Chemical" by the US EPA. GP has already received approval from the US EPA under its Section 18 Public Health Emergency Exemption program for use in seven states. This study characterizes the efficacy of GP for inactivating MS2 bacteriophage─a nonenveloped virus widely used as a surrogate for SARS-CoV-2. Experiments measured the decrease in airborne viable MS2 concentration in the presence of different concentrations of GP from 60 to 90 min, accounting for both natural die-off and settling of MS2. Experiments were conducted both by introducing GP aerosol into air containing MS2 and by introducing airborne MS2 into air containing GP aerosol. GP is consistently able to rapidly reduce viable MS2 bacteriophage concentration by 2-3 logs at GP concentrations of 0.04-0.5 mg/m³ (corresponding to TEG concentrations of 0.025 to 0.287 mg/m³). Related GP efficacy experiments by the US EPA, as well as GP (TEG) safety and toxicology, are also discussed.

SUBMITTER: Desai G

PROVIDER: S-EPMC10001433 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Efficacy of Grignard Pure to Inactivate Airborne Phage MS2, a Common SARS-CoV-2 Surrogate.

Desai Grishma G Ramachandran Gurumurthy G Goldman Emanuel E Esposito William W Galione Antony A Lal Altaf A Choueiri Toni K TK Fay Andre A Jordan William W Schaffner Donald W DW Caravanos Jack J Grignard Etienne E Mainelis Gediminas G

Environmental science & technology 20230228 10

Grignard Pure (GP) is a unique and proprietary blend of triethylene glycol (TEG) and inert ingredients designed for continuous antimicrobial treatment of air. TEG has been designated as a ″Safer Chemical" by the US EPA. GP has already received approval from the US EPA under its Section 18 Public Health Emergency Exemption program for use in seven states. This study characterizes the efficacy of GP for inactivating MS2 bacteriophage─a nonenveloped virus widely used as a surrogate for SARS-CoV-2. ...[more]

PMID: 36853925

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Project description:ObjectiveUsing a battery of preclinical tests to support development of a light-based treatment for COVID-19, establish a range of 425 nm light doses that are non-hazardous to the tissues of the oral cavity and assess whether a 425 nm light dose in this non-hazardous range can inactivate SARS-CoV-2 in artificial saliva.MethodsThe potential hazards to oral tissues associated with a range of acute 425 nm light doses were assessed using a battery of four preclinical tests: (1) cytotoxicity, using well-differentiated human large airway and buccal epithelial models; (2) toxicity to commensal oral bacteria, using a panel of model organisms; (3) light-induced histopathological changes, using ex vivo porcine esophageal tissue, and (4) thermal damage, by dosing the oropharynx of intact porcine head specimens. Then, 425 nm light doses established as non-hazardous using these tests were evaluated for their potential to inactivate SARS-CoV-2 in artificial saliva.ResultsA dose range was established at which 425 nm light is not cytotoxic in well-differentiated human large airway or buccal epithelial models, is not cytotoxic to a panel of commensal oral bacteria, does not induce histopathological damage in ex vivo porcine esophageal tissue, and does not induce thermal damage to the oropharynx of intact porcine head specimens. Using these tests, no hazards were observed for 425 nm light doses less than 63 J/cm2 delivered at irradiance less than 200 mW/cm2. A non-hazardous 425 nm light dose in this range (30 J/cm2 at 50 mW/cm2) was shown to inactivate SARS-CoV-2 in vitro in artificial saliva.ConclusionPreclinical hazard assessments and SARS-CoV-2 inactivation efficacy testing were combined to guide the development of a 425 nm light-based treatment for COVID-19.Clinical significanceThe process used here to evaluate the potential hazards associated with 425 nm acute light dosing of the oral cavity to treat COVID-19 can be extended to other wavelengths, anatomical targets, and therapeutic applications to accelerate the development of novel photomedicine treatments.

Project description:Background: The peptide MS2-L represents toxins of the ssRNA Leviviridae phage family and consists of a predicted N-terminal soluble domain followed by a transmembrane domain. MS2-L mediates bacterial cell lysis through the formation of large lesions in the cell envelope, but further details of this mechanism as a prerequisite for applied bioengineering studies are lacking. The chaperone DnaJ is proposed to modulate MS2-L activity, whereas other cellular targets of MS2-L are unknown. Methods: Here, we provide a combined in vitro and in vivo overexpression approach to reveal molecular insights into MS2-L action and its interaction with DnaJ. Full-length MS2-L and truncated derivatives were synthesized cell-free and co-translationally inserted into nanodiscs or solubilized in detergent micelles. By native liquid bead ion desorption mass spectrometry, we demonstrate that MS2-L assembles into high oligomeric states after membrane insertion. Results: Oligomerization is directed by the transmembrane domain and is impaired in detergent environments. Studies with truncated MS2-L derivatives provide evidence that the soluble domain acts as a modulator of oligomer formation. DnaJ strongly interacts with MS2-L in membranes as well as in detergent environments. However, this interaction affects neither the MS2-L membrane insertion efficiency nor its oligomerization in nanodisc membranes. In accordance with the in vitro data, the assembly of MS2-L derivatives into large membrane located clusters was monitored by overexpression of corresponding fusions with fluorescent monitors in E. coli cells. Analysis by cryo-electron microscopy indicates that lesion formation is initiated in the outer membrane, followed by disruption of the peptidoglycan layer and disintegration of the inner membrane. Conclusion: MS2-L forms oligomeric complexes similar to the related phage toxin ΦX174-E. The oligomeric interface of both peptides is located within their transmembrane domains. We propose a potential function of the higher-order assembly of small phage toxins in membrane disintegration and cell lysis.

Project description:One of the most important measures implemented to reduce SARS-CoV-2 transmission has been the use of face masks. Yet, most mask options available in the market display a passive action against the virus, not actively compromising its viability. Here, we propose to overcome this limitation by incorporating antiviral essential oils (EOs) within polycaprolactone (PCL) electrospun fibrous mats to be used as intermediate layers in individual protection masks. Twenty EOs selected based on their antimicrobial nature were examined for the first time against the Escherichia coli MS2 virus (potential surrogate of SARS-CoV-2). The most effective were the lemongrass (LGO), Niaouli (NO) and eucalyptus (ELO) with a virucidal concentration (VC) of 356.0, 365.2 and 586.0 mg/mL, respectively. PCL was processed via electrospinning, generating uniform, beadless fibrous mats. EOs loading was accomplished via two ways: (1) physisorption on pre-existing mats (PCLaEOs), and (2) EOs blending with the polymer solution prior to fiber electrospinning (PCLbEOs). In both cases, 10% v/v VC was used as loading concentration, so the mats' stickiness and overwhelming smell could be prevented. The EOs presence and release from the mats were confirmed by UV-visible spectroscopy (≈5257-631 µg) and gas chromatography-mass spectrometry evaluations (average of ≈14.3% EOs release over 4 h), respectively. PCLbEOs mats were considered the more mechanically and thermally resilient, with LGO promoting the strongest bonds with PCL (PCLbLGO). On the other hand, PCLaNO and PCLaELO were deemed the least cohesive combinations. Mats modified with the EOs were all identified as superhydrophobic, capable of preventing droplet penetration. Air and water-vapor permeabilities were affected by the mats' porosity (PCL < PCLaEOs < PCLbEOs), exhibiting a similar tendency of increasing with the increase of porosity. Antimicrobial testing revealed the mats' ability to retain the virus (preventing infiltration) and to inhibit its action (log reduction averaging 1). The most effective combination against the MS2 viral particles was the PCLbLGO. These mats' scent was also regarded as the most pleasant during sensory evaluation. Overall, data demonstrated the potential of these EOs-loaded PCL fibrous mats to work as COVID-19 active barriers for individual protection masks.

Dataset Information

Efficacy of Grignard Pure to Inactivate Airborne Phage MS2, a Common SARS-CoV-2 Surrogate.

Publications

Efficacy of Grignard Pure to Inactivate Airborne Phage MS2, a Common SARS-CoV-2 Surrogate.

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