How severe a viral infection is depends on how much the virus is replicating, damaging cells as it does so, and on the response of the immune system. Or so one would think. “Some of the most severe cases of COVID-19 are happening in the absence of replicating virus,” Joseph Guarnieri told BioWorld. In work published in Science Translational Medicine on Aug. 9, 2023, Guarnieri and his colleagues have described how those severe cases unfold, even as there is no replicating virus to be found.
TYK Medicines Inc. has described transcriptional coactivator YAP1/transcriptional enhancer factor (TEAD) interaction inhibitors reported to be useful for the treatment of cancer.
Annexon Inc. has identified boronic acid derivatives acting as complement C1s subcomponent inhibitors reported to be useful for the treatment of neurodegeneration, inflammatory, eye, metabolic and autoimmune diseases.
Researchers from Bristol Myers Squibb Co. presented the discovery and preclinical evaluation of a novel diacylglycerol kinases (DGK) α and ζ dual inhibitors.
Researchers from the U.S. National Institutes of Health and collaborators recently conducted a study investigating the mechanisms of HIV-1 resistance to integrase strand transfer inhibitors (INSTIs), such as the approved drug dolutegravir (DTG). They focused on understanding the mechanisms of resistance caused by mutations at positions 138, 140, and 148 and analyzed combinations of the mutations E138K, G140A/S, and Q148H/K/R, all conferring resistance to INSTIs.
The role of the enzyme γ-secretase in neuronal cholesterol metabolism could have a beneficial effect on the synapse that has not yet been explored in Alzheimer’s disease (AD). On Aug. 4, 2023, scientists at Stanford University School of Medicine and the Howard Hughes Medical Institute published a study online in Neuron that linked cholesterol levels in the brain to synaptic dysfunction in AD.
Researchers at Merck & Co. Inc. have presented the discovery of novel selective metabotropic glutamate receptor 2 (mGluR2) negative allosteric modulators (NAMs) as potential PET imaging agents. Synthesis and optimization of a series of analogues of a potent and selective mGluR2 NAM resulted in the identification of compound MK-8056 as a high-affinity mGluR2 NAM (Ki=0.19 nM) with desirable lipophilicity (logD7.0=2.46) and low P-gp susceptibility.
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