Evaluation of disinfection methods for personal protective equipment (PPE) items for reuse during a pandemic.

The COVID-19 pandemic resulted in many supply chain issues, including crippling of essential personal protective equipment (PPE) needed for high-risk occupations such as those in healthcare. As a result of these supply chain issues, unprecedented crisis capacity strategies were implemented to divert PPE items such as filtering facepiece respirators (FFRs, namely N95s) to those who needed them most for protection. Large-scale methods for decontamination were used throughout the world to preserve these items and provided for their extended use. The general public also adopted the use of non-specialized protective equipment such as face coverings. So, the need for cleaning, decontamination, or disinfection of these items in addition to normal clothing items became a necessary reality. Some items could be laundered, but other items were not appropriate for washing/drying. To fill research gaps in small-scale, non-commercial cleaning and disinfection, this bench-scale research was conducted using small coupons (swatches) of multiple PPE/barrier protection materials inoculated with virus (non-pathogenic bacteriophages Phi6 and MS2) and tested against a range of decontamination methods including bleach-, alcohol- and quaternary ammonium compound (QAC)-based liquid sprays, as well as low concentration hydrogen peroxide vapor (LCHPV) and bench-scale laundering. In general, non-porous items were easier to disinfect than porous items, and the enveloped virus Phi6 was overall easier to inactivate than MS2. Multiple disinfection methods were shown to be effective in reducing viral loads from PPE coupons, though only laundering and LCHPV were effective for all materials tested that were inoculated with Phi6. Applications of this and follow-on full-scale research are to provide simple effective cleaning/disinfection methods for use during the current and future pandemics.

Determining Viral Disinfection Efficacy of Hot Water Laundering.

This protocol provides an example of a laboratory process for conducting laundering studies that generate data on viral disinfection. While the protocol was developed for research during the coronavirus disease 2019 (COVID-19) pandemic, it is intended to be a framework, adaptable to other virus disinfection studies; it demonstrates the steps for preparing the test virus, inoculating the test material, assessing visual and integrity changes to the washed items due to the laundering process, and quantifying the reduction in viral load. Additionally, the protocol outlines the necessary quality control samples for ensuring the experiments are not biased by contamination and measurements/observations that should be recorded to track the material integrity of the personal protective equipment (PPE) items after multiple laundering cycles. The representative results presented with the protocol use the Phi6 bacteriophage inoculated onto cotton scrub, denim, and cotton face-covering materials and indicate that the hot water laundering and drying process achieved over a 3-log (99.9%) reduction in viral load for all samples (a 3-log reduction is the disinfectant performance metric in U.S. Environmental Protection Agency's Product Performance Test Guideline 810.2200). The reduction in viral load was uniform across different locations on the PPE items. The results of this viral disinfection efficacy testing protocol should help the scientific community explore the effectiveness of home laundering for other types of test viruses and laundering procedures.

Evaluation of electrostatic sprayers and foggers for the application of disinfectants in the era of SARS-CoV-2.

Although research has shown that the COVID-19 disease is most likely caused by airborne transmission of the SARS-CoV-2 virus, disinfection of potentially contaminated surfaces is also recommended to limit the spread of the disease. Use of electrostatic sprayers (ESS) and foggers to rapidly apply disinfectants over large areas or to complex surfaces has emerged with the COVID-19 pandemic. ESSs are designed to impart an electrostatic charge to the spray droplets with the goal of increasing deposition of the droplets onto surfaces, thereby promoting more efficient use of the disinfectant. The purpose of this research was to evaluate several spray parameters for different types of sprayers and foggers, as they relate to the application of disinfectants. Some of the parameters evaluated included the spray droplet size distribution, the electrostatic charge, the ability of the spray to wrap around objects, and the loss of disinfectant chemical active ingredient due to the spray process. The results show that most of the devices evaluated for droplet size distribution had an average volume median diameter ≥ 40 microns, and that four out of the six ESS tested for charge/mass produced sprays of at least 0.1 mC/kg. A minimal wrap-around effect of the spray deposition onto a cylindrical object was observed. The loss of disinfectant active ingredient to the air due to spraying was minimal for the two disinfectants tested, and concurrently, the active ingredient concentrations of the liquid disinfectants sprayed and collected 3 feet (1 meter) away from the spray nozzle do not decrease.

Discovery of indazoles as inhibitors of Tpl2 kinase.

Synthesis, modeling and structure-activity relationship of indazoles as inhibitors of Tpl2 kinase are described. From a high throughput screening effort, we identified an indazole hit compound 5 that has a single digit micromolar Tpl2 activity. Through SAR modifications at the C3 and C5 positions of the indazole, we discovered compound 31 with good potency in LANCE assay and cell-based p-Erk assay.