Structural Studies of Inhibitors with Clinically Relevant Influenza Endonuclease Variants.

Vital to the treatment of influenza is the use of antivirals such as Oseltamivir (Tamiflu) and Zanamivir (Relenza); however, antiviral resistance is becoming an increasing problem for these therapeutics. The RNA-dependent RNA polymerase acidic N-terminal (PA) endonuclease, a critical component of influenza viral replication machinery, is an antiviral target that was recently validated with the approval of Baloxavir Marboxil (BXM). Despite its clinical success, BXM has demonstrated susceptibility to resistance mutations, specifically the I38T, E23K, and A36 V mutants of PA.

Correction: Masking thiol reactivity with thioamide, thiourea, and thiocarbamate-based MBPs.

Correction for 'Masking thiol reactivity with thioamide, thiourea, and thiocarbamate-based MBPs' by Hyeonglim Seo , , 2023, , 2283-2286, https://doi.org/10.1039/D2CC06596G.

Development of Human Carbonic Anhydrase II Heterobifunctional Degraders.

Human carbonic anhydrase II (hCAII) is a metalloenzyme essential to critical physiological processes in the body. hCA inhibitors are used clinically for the treatment of indications ranging from glaucoma to epilepsy. Targeted protein degraders have emerged as a promising means of inducing the degradation of disease-implicated proteins by using the endogenous quality control mechanisms of a cell.

Masking thiol reactivity with thioamide, thiourea, and thiocarbamate-based MBPs.

Thioamides, thioureas, and thiocarbamates are introduced as stable, sulfur-based metal-binding pharmacophores (MBPs) for use in metalloenzyme fragment-based drug discovery (mFBDD). MBP reactivity, bioactivity, and structural studies show that these molecules can act as ligands for Zn(II)-dependent metalloenzymes including human carbonic anhydrase II (hCAII) and matrix metalloproteinase-2 (MMP-2).

Carboxylic Acid Isostere Derivatives of Hydroxypyridinones as Core Scaffolds for Influenza Endonuclease Inhibitors.

Among the most important influenza virus targets is the RNA-dependent RNA polymerase acidic N-terminal (PA) endonuclease, which is a critical component of the viral replication machinery. To inhibit the activity of this metalloenzyme, small-molecule inhibitors employ metal-binding pharmacophores (MBPs) that coordinate to the dinuclear Mn active site. In this study, several metal-binding isosteres (MBIs) were examined where the carboxylic acid moiety of a hydroxypyridinone MBP is replaced with other groups to modulate the physicochemical properties of the compound.

Correction: F-Tagged metal binding pharmacophores for NMR screening of metalloenzymes.

Correction for 'F-Tagged metal binding pharmacophores for NMR screening of metalloenzymes' by Kathleen E. Prosser , , 2021, , 4934-4937, DOI: 10.1039/D1CC01231B.