In vitro evaluation of the activity of teriflunomide against SARS-CoV-2 and the human coronaviruses 229E and OC43

Previous data have suggested an antiviral effect of teriflunomide, including against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the agent underlying the ongoing COVID-19 pandemic. We undertook an in vitro investigation to evaluate the inhibitory activity of teriflunomide against SARS-CoV-2 in a cell-based assay. Teriflunomide was added to Vero (kidney epithelial) cells that had been infected with SARS-CoV-2. A nucleocapsid immunofluorescence assay was performed to examine viral inhibition with teriflunomide and any potential cytotoxic effect. The 50% effective concentration (EC(50)) for teriflunomide against SARS-CoV-2 was 15.22 μM. No cytotoxicity was evident for teriflunomide in the Vero cells (i.e., the 50% cytotoxic concentration [CC(50)] was greater than the highest test concentration of 100 μM). The data were supported by additional experiments using other coronaviruses and human cell lines. In the SARS-CoV-2-infected Vero cells, the prodrug leflunomide had an EC(50) of 16.49 μM and a CC(50) of 54.80 μM. Our finding of teriflunomide-mediated inhibition of SARS-CoV-2 infection at double-digit micromolar potency adds to a growing body of evidence for a broad-ranging antiviral effect of teriflunomide.

Nitric-oxide enriched plasma-activated water inactivates 229E coronavirus and alters antiviral response genes in human lung host cells

The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach for viral inactivation, based on plasma technology, was considered. A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water (NO-PAW), the effects of which on coronaviruses, have not been reported to date. To determine these effects, alpha-HCoV-229E was used in an experimental model. We found that NO-PAW treatment effectively inhibited coronavirus infection in host lung cells, visualized by evaluating the cytopathic effect and expression level of spike proteins. Interestingly, NO-PAW showed minimal toxicity towards lung host cells, suggesting its potential for therapeutic application. Moreover, this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses. Together, our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments, including such coronaviruses. © 2022 The Authors

Positive predictive value of rapid antigen tests in school during SARS-CoV-2 Omicron variant surge

In Korea, we conducted a national observational study to calculate the positive predictive value of SARS-CoV-2 rapid antigen tests in K-12 schools during the Omicron variant surge in March 2022. The weekly positive predictive value ranged from 86.4% to 93.2%. The positive predictive value was the highest among elementary school students with symptoms (95.7%) and lowest among teachers/staff without symptoms (70.9%). .

BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies

Bruton's tyrosine kinase (BTK) is an essential component of multiple signaling pathways that regulate B cell and myeloid cell proliferation, survival, and functions, making it a promising therapeutic target for various B cell malignancies and inflammatory diseases. Five small molecule inhibitors have shown remarkable efficacy and have been approved to treat different types of hematological cancers, including ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, and orelabrutinib. The first-in-class agent, ibrutinib, has created a new era of chemotherapy-free treatment of B cell malignancies. Ibrutinib is so popular and became the fourth top-selling cancer drug worldwide in 2021. To reduce the off-target effects and overcome the acquired resistance of ibrutinib, significant efforts have been made in developing highly selective second- and third-generation BTK inhibitors and various combination approaches. Over the past few years, BTK inhibitors have also been repurposed for the treatment of inflammatory diseases. Promising data have been obtained from preclinical and early-phase clinical studies. In this review, we summarized current progress in applying BTK inhibitors in the treatment of hematological malignancies and inflammatory disorders, highlighting available results from clinical studies.

Convenient Synthesis of Ellagic Acid from Methyl Gallate and SARS-CoV-2 3CLpro Antiviral Activity

A practical synthesis of ellagic acid has been achieved from methyl gallate by a proposed synthetic route of five steps, consisting of ketal protection, regioselective bromination, bis-lactonization, C-C bond formation between the aromatic rings of the galloyl groups, and ketal deprotection, in 38% overall yield. Ellagic acid showed a slight inhibitory activity against SARS-CoV-2 3CLpro. © 2022. Thieme. All rights reserved.