ABSTRACT
Objective The current global COVID-19 pandemic has disrupted supply chains and the production of essential goods and services. This includes personal protective equipment (PPE) kits, respirators, and other protective devices. Hence efforts were made to prototype and produce 3D-printed N95 respirators to fill the gap in supply. In addition, methods of sterilization were put into place for the respirators. As well as forming standard operating procedures. Methods With the use of vast open-source libraries and collaboration with engineers and doctors fighting the COVID-19 pandemic, respirator prototypes were produced with special consideration to the sizing to fit median facial sizes. Polymer plastics were mixed in various proportions to condition the respirator to be used by frontline workers in austere environments. Due to the shortage of medical-grade filter media, alternative sources were researched. Merv 13 and Merv 15 filters were selected due to their cheap costs, vast abundance, and proven filtration efficacy against particles of 0.03 microns. Studies conducted around the world have also shown its efficacy as an alternative to medical-grade air filter media. After developing standard operating procedures (SOPs) for sterilisation and respirator usage. Emergency approval was obtained and a limited number of healthcare workers were issued with this respirator (n=400). PPE kit satisfaction and self-efficacy scores were calculated from daily questionnaires during donning and doffing Results Qualitative fit-tests in all 400 healthcare workers matched those of a conventional N95 respirator. Almost all of the respondents in the PPE kit satisfaction responded positively. The self-efficacy score calculated from the general self-efficiency scale had an overall positive value, with the average score being 4.29. This demonstrated that the self-efficacy score was above average and indicated a high motivation to overcome obstacles and spend more time solving problems. The average self-efficacy score is defined between 2.5 - 3.5, and a low self-efficacy score is defined as a score below 2.5. Lastly, a regression analysis was done to test the correlation between PPE kit satisfaction and self-efficiency this demonstrated a positive correlation between PPE kit satisfaction using the 3D-printed respirator and self-efficacy (Slope: 0.416, Intercept: -1.066, R-value: 0.872, P-value: <0.01) Conclusions With supply chain disruptions and reduced or nonexistent supplies of essential medical goods. The need of a reusable, sterilisable, and efficient respirator has never been more evident. The materials used have made it sustain heavy use in austere environments. Studies have reported higher than average burnout rates in COVID-19-based healthcare workers. Studies have also shown that the rates of burnout are high in healthcare professionals without access to proper PPE kits in developing nations. This respirator was rated highly in PPE kit satisfaction and the self-efficacy score. Studies have demonstrated a correlation between high self-efficacy scores and low burnout rates in health care workers. There is also documented evidence of a positive correlation between high self-efficacy scores and general health. As the pandemic continues to evolve, so will the efforts to combat it, such as 3D printing. Interdisciplinary collaboration continues to drive our efforts to combat the pandemic and hopefully resolve it in the future.
ABSTRACT
Herpes simplex virus 1 (HSV-1) and HSV-2 remain major human pathogens despite the development of anti-HSV therapeutics as some of the first antiviral drugs. Current therapies are incompletely effective and frequently drive the evolution of drug-resistant mutants. We recently determined that certain natural troponoid compounds such as ß-thujaplicinol readily suppress HSV-1 and HSV-2 replication. Here, we screened 26 synthetic α-hydroxytropolones with the goals of determining a preliminary structure-activity relationship for the α-hydroxytropolone pharmacophore and providing a starting point for future optimization studies. Twenty-five compounds inhibited HSV-1 and HSV-2 replication at 50 µM, and 10 compounds inhibited HSV-1 and HSV-2 at 5 µM, with similar inhibition patterns and potencies against both viruses being observed. The two most powerful inhibitors shared a common biphenyl side chain, were capable of inhibiting HSV-1 and HSV-2 with a 50% effective concentration (EC50) of 81 to 210 nM, and also strongly inhibited acyclovir-resistant mutants. Moderate to low cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC50] of 50 to >100 µM). Therapeutic indexes ranged from >170 to >1,200. These data indicate that troponoids and specifically α-hydroxytropolones are a promising lead scaffold for development as anti-HSV drugs provided that toxicity can be further minimized. Troponoid drugs are envisioned to be employed alone or in combination with existing nucleos(t)ide analogs to suppress HSV replication far enough to prevent viral shedding and to limit the development of or treat nucleos(t)ide analog-resistant mutants.
