ABSTRACT
Mutations in the nucleocapsid of SARS-CoV-2 may interfere with antigen detection by diagnostic tests. We used several methods to evaluate the effect of various SARS-CoV-2 nucleocapsid mutations on the performance of the Panbio™ and BinaxNOW™ lateral flow rapid antigen tests and a prototype high-throughput immunoassay that utilizes Panbio antibodies. Variant detection was also evaluated by immunoblot and BIAcore™ assay. A panel of 23 recombinant nucleocapsid antigens (rAgs) were produced that included mutations found in circulating SARS-CoV-2 variants, including variants of concern. All mutant rAgs were detected by all assays, at a sensitivity equivalent to wild-type control (Wuhan strain). Thus, using a rAg approach, we found that the SARS-CoV-2 nucleocapsid mutations examined do not directly impact antigen detection or antigen assay performance.
Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/diagnosis , COVID-19/genetics , COVID-19 Testing , Diagnostic Tests, Routine , Humans , Mutation , Nucleocapsid/genetics , SARS-CoV-2/genetics , Sensitivity and SpecificityABSTRACT
Following the discovery of a metabolic 'soft-spot' on a bicyclo[2.2.2]octyltriazole lead, an extensive effort was undertaken to block the oxidative metabolism and improve PK of this potent HSD1 lead. In this communication, SAR survey focusing on various alkyl chain replacements will be detailed. This effort culminated in the discovery of a potent ethyl sulfone inhibitor with an improved PK profile across species and improved physical properties.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors , Bridged Bicyclo Compounds/chemistry , Enzyme Inhibitors/chemistry , Metabolic Syndrome/drug therapy , Triazoles/chemistry , 11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , 11-beta-Hydroxysteroid Dehydrogenase Type 2/antagonists & inhibitors , 11-beta-Hydroxysteroid Dehydrogenase Type 2/metabolism , Animals , Enzyme Inhibitors/pharmacokinetics , Enzyme Inhibitors/therapeutic use , Humans , Mice , Structure-Activity Relationship , Triazoles/pharmacokinetics , Triazoles/therapeutic useABSTRACT
Here, we report a novel strategy for the combinatorial or parallel solid-phase synthesis of potential inhibitors of the mur-pathway enzymes. The strategy involves the efficient use of p-alkoxybenzylidene acetal linker for reversible immobilization of sugar scaffolds to solid phase. This methodology was used to synthesize several glycopeptides on solid phase in good yields.