Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro.

Remdesivir (GS-5734; VEKLURY) is a single diastereomer monophosphoramidate prodrug of an adenosine analog (GS-441524). Remdesivir is taken up by target cells and metabolized in multiple steps to form the active nucleoside triphosphate (GS-443902), which acts as a potent inhibitor of viral RNA-dependent RNA polymerases. Remdesivir and GS-441524 have antiviral activity against multiple RNA viruses.

Uncovering a multitude of human glucocorticoid receptor variants: an expansive survey of a single gene.

Background: Glucocorticoids are commonly used in the clinical setting for their potent anti-inflammatory effects; however, significant variations in response to treatment have been demonstrated. Although the underlying mechanisms have yet to be fully understood, this variable response may be a result of alterations in human glucocorticoid receptor (hGR) expression and function. In addition to hGRα, the biologically active isoform, a screening of current databases and publications revealed five alternative splice isoforms and hundreds of variants that have been reported to date.

Lipopolysaccharide Stress Induces Cryptic Exon Splice Variants of the Human Glucocorticoid Receptor.

Glucocorticoids are widely used in the treatment of numerous inflammatory conditions, including sepsis. Unfortunately, patient response to glucocorticoid therapy can be inconsistent. Variations in the human glucocorticoid receptor (hGR) may contribute to the differential patient response.

A novel human glucocorticoid receptor SNP results in increased transactivation potential.

Glucocorticoids are one of the most widely used therapeutics in the treatment of a variety of inflammatory disorders. However, it is known that there are variable patient responses to glucocorticoid treatment; there are responders and non-responders, or those that need higher dosages. Polymorphisms in the glucocorticoid receptor (GR) have been implicated in this variability.

A Tri-Nucleotide Pattern in a 3' UTR Segment Affects The Activity of a Human Glucocorticoid Receptor Isoform.

We previously identified a truncated human glucocorticoid receptor (hGR) isoform of 118 amino acids, hGR-S1(-349A), that despite lacking the major functional domains, was more hyperactive after glucocorticoid treatment than the full-length receptor. Furthermore, its 3' untranslated region (UTR) was required. To dissect the underlying mechanisms for hyperactivity, a series of hGR isoforms with consecutive deletions in the 3' UTR were created to test their transactivation potential using reporter assays.

Hyperactive Human Glucocorticoid Receptor Isoforms and their Implications for the Stress Response.

Glucocorticoids are indispensable therapeutic agents in diseases of inflammation, but their effectiveness in treating advanced septic shock has been inconsistent. Our understanding of the mechanisms causing this variability to steroid therapy remains limited. Previous studies in our laboratory have implicated human glucocorticoid receptor (hGR) polymorphisms as one of the likely reasons for this variability.