Prodrug nanotherapy demonstrates anticryptosporidial efficacy in a mouse model of chronic infection.

The gastrointestinal disease cryptosporidiosis, caused by the genus , is a common cause of diarrheal diseases in children, particularly in developing countries and frequently fatal in immunocompromised individuals. ()-specific bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) has been a molecular target for inhibitor design. (.

Monte Carlo simulations for free energies of hydration: Past to present.

A summary of the development of Monte Carlo statistical mechanics simulations for the computation of free energies of hydration of organic molecules is followed by presentation of results with the latest version of the optimized potentials for liquid simulations-all atom force field and the TIP4P water model. Scaling of the Lennard-Jones interactions between water, oxygen, and carbon atoms by a factor of 1.25 is found to improve the accuracy of free energies of hydration for 50 prototypical organic molecules from a mean unsigned error of 1.

Structure-Activity Relationships, Deuteration, and Fluorination of Synthetic Cannabinoid Receptor Agonists Related to AKB48, 5F-AKB-48, and AFUBIATA.

Synthetic cannabinoid receptor agonists (SCRAs) are a growing class of new psychoactive substances (NPS) commonly derived from an -alkylated indole, indazole, or 7-azaindole scaffold. Diversification of this core (at the 3-position) with amide-linked pendant amino acid groups and modular -alkylation (of the indole/indazole/7-azaindole core) ensures that novel SCRAs continue to enter the illicit drug market rapidly. In response to the large number of SCRAs that have been detected, pharmacological evaluation of this NPS class has become increasingly common.

Proof-of-concept studies with a computationally designed M inhibitor as a synergistic combination regimen alternative to Paxlovid.

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (M) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug.