Pyrazinyl-Substituted Aminoazoles as Covalent Inhibitors of Thrombin: Synthesis, Structure, and Anticoagulant Properties.

This study presents a novel series of -acylated 1,2,4-triazol-5-amines and 1-pyrazol-5-amines, featuring a pyrazin-2-yl moiety, developed as covalent inhibitors of thrombin. These compounds demonstrated potent inhibitory activity, with derivatives and achieving IC values as low as 0.7 and 0.

Design, Synthesis, and Unprecedented Interactions of Covalent Dipeptide-Based Inhibitors of SARS-CoV-2 Main Protease and Its Variants Displaying Potent Antiviral Activity.

The main protease (M) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 M inhibitors, including compounds (IC = 0.

A multiplex method for rapidly identifying viral protease inhibitors.

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation.

Communicating therapeutic indication information in direct-to-consumer television ads for prescription cancer drugs: Exploring the effect of dual-modality presentations.

Objective: The rise in direct-to-consumer (DTC) ads for cancer drugs, which often have complex indications, raises concerns about consumer misunderstanding. A drug's indication must clearly convey its condition(s) of use, which may include elements such as the approved patient population, second-line treatment status, and whether it is adjunctive or concomitant therapy. The study examines whether the modality used to communicate the drug's indication in DTC television ads affects consumers' recognition, recall, and comprehension.