The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2.

The spurious acquisition and optimization of a furin cleavage site in the SARS-CoV-2 spike protein is associated with increased viral transmission and disease, and has generated intense interest in the development and application of therapeutic furin inhibitors to thwart the COVID-19 pandemic. This review summarizes the seminal studies that informed current efforts to inhibit furin. These include the convergent efforts of endocrinologists, virologists, and yeast geneticists that, together, culminated in the discovery of furin. We describe the pioneering biochemical studies which led to the first furin inhibitors that were able to block the disease pathways which are broadly critical for pathogen virulence, tumor invasiveness, and atherosclerosis. We then summarize how these studies subsequently informed current strategies leading to the development of small-molecule furin inhibitors as potential therapies to combat SARS-CoV-2 and other diseases that rely on furin for their pathogenicity and progression.

Low-dose naltrexone reduced anxiety in persons with multiple sclerosis during the COVID-19 pandemic.

Persons with multiple sclerosis (PwMS) have been considered at high risk for vaccination and/or acquisition of COVID-19 related to their reduced immune systems and daily regimen of immune suppressing therapy. Substantiated and unsubstantiated reports on these unknown circumstances increased anxiety and depression. Low-dose naltrexone (LDN) is a potentially effective off-label therapy shown to be effective at controlling fatigue for several autoimmune disorders including MS. This study utilized a small population of PwMS from central Pennsylvania in order to determine whether LDN therapy altered their perceived anxiety or depression during the early months of COVID-19. Utilizing mailed surveys, self-reported anxiety and depression scores were found to be significantly lower for PwMS who were prescribed LDN either alone or as an adjuvant to a standard disease modifying therapy (DMT) in comparison to those on oral disease-modifying therapies (DMTs). The data suggest that the non-toxic, inexpensive biotherapeutic may be beneficial in lessening anxiety.

The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2

The spurious acquisition and optimization of a furin cleavage site in the SARS-CoV-2 spike protein is associated with increased viral transmission and disease, and has generated intense interest in the development and application of therapeutic furin inhibitors to thwart the COVID-19 pandemic. This review summarizes the seminal studies that informed current efforts to inhibit furin. These include the convergent efforts of endocrinologists, virologists, and yeast geneticists that, together, culminated in the discovery of furin. We describe the pioneering biochemical studies which led to the first furin inhibitors that were able to block the disease pathways which are broadly critical for pathogen virulence, tumor invasiveness, and atherosclerosis. We then summarize how these studies subsequently informed current strategies leading to the development of small-molecule furin inhibitors as potential therapies to combat SARS-CoV-2 and other diseases that rely on furin for their pathogenicity and progression.

Significant increase in the incidence of high-risk pulmonary embolism during the COVID-19 shutdown: the pandemic response causes serious collateral consequences (preprint)

Background Strict stay-at-home rules, along with fear of coronavirus infection, have kept many patients from timely seeking medical attention during the novel coronavirus disease (COVID-19) pandemic. This situation may have led to an increase in the number of patients arriving at hospital in deteriorated clinical condition. In this regard, we aimed to investigate the incidence of pulmonary embolism (PE) patients defined as high-risk according to the European Society of Cardiology (ESC) presenting at our emergency department during the shutdown.Methods A retrospective data analysis explored the impact of the COVID-19 shutdown on the presentation of acute PE patients admitted to University Hospital Graz, Austria. We compared percentages of high-risk PE patients admitted during shutdown and during two control periods: the corresponding period in 2019 and an earlier period in 2020. By including data from the previous year, a general increase of high risk PE cases in 2020 compared to 2019 was ruled out. Risk assessment was carried out in accordance with current ESC guidelines for the diagnosis and management of acute PE.Results The percentage of patients with high-risk PE increased significantly during the COVID-19 shutdown period compared to the two control periods (p = 0.003; p = 0.011). Time from onset of symptoms to hospital admission was significantly longer in the study period compared to the control periods (p = 0.046 and p = 0.044, respectively).Conclusion The current findings indicate a significant increase in high-risk PE cases as well as delayed hospital admission of symptomatic PE patients during the COVID-19 shutdown period.