A Procoagulant Peptide Analog of the SARS-CoV-2 Nucleocapsid C-terminal Domain

Structural basis for the procoagulant activity of Staphylococcus aureus staphylocoagulase

3D models of the C-terminal SC region suggest that the major C-terminal domain of SC folds into a single-layer β-sheet structurally similar to the membrane occupation and recognition nexus (MORN) family of tandem repeats, which is critical for understanding SC-mediated fibrin generation.

Unraveling A4GALT Mechanism and Its Modulation With Adamantyl-Galactosylceramide Analogues: Advancing Fabry Disease Therapeutic Strategies.

The molecular mechanism of human A4GALT is revealed at atomic detail using QM/MM simulations, revealing a conformational rearrangement involving a 310-helix that stabilizes the donor substrate and promotes a front-face SNi-like catalytic mechanism, in which a short-lived oxocarbenium-ion intermediate forms.

Biomaterials and Biosystems

Novel salicylamido sulfonamides as CD73 immune checkpoint inhibitors: Synthesis and in vitro biological evaluation.

The immune checkpoint enzyme CD73 plays a crucial role in the adenosine (ADO) metabolic pathway by catalyzing the conversion of AMP to adenosine. Dysregulated CD73 activity elevates extracellular ADO in the tumor microenvironment, driving immunosuppression and tumor immune evasion, highlighting CD73 as a key immunotherapeutic target. In this study, we report the design and synthesis of a novel series of salicylamido sulfonamide-based small-molecule CD73 inhibitors. The in vitro CD73 inhibitory assay reveals that SA-41 and SA-26 exhibited potent activity with IC50 values of 2.83 ± 0.45 μM and 2.96 ± 0.46 μM, respectively. Molecular docking and dynamic simulations revealed that SA-26 maintained stable interactions with CD73 throughout a 100-ns simulation with no significant deviation. Furthermore, in silico ADME analysis indicated that both lead compounds possess favourable drug-like properties, with no Lipinski's rule-of-five violations, balanced lipophilicity, and acceptable predicted oral absorption, supporting their pharmacokinetic potential. These findings highlight SA-26 and SA-41 as promising candidates for further development as non- nucleotide-based small-molecule CD73 inhibitors.

Amantadine-induced reorganization of model SARS-CoV-2 lipid envelopes

Results show that amantadine interactions with simplified SARS-CoV-2 lipid envelopes depend on both the net charge of the lipid headgroup and the membrane organization, which is influenced by the presence or absence of unsaturated alkyl chains in the hydrophobic region.

Expression of Active Apurinic Apyrimidinic Endodeoxyribonuclease 1 in Human Platelets

The first evidence for the expression levels and subcellular localization of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), evaluated alongside cytosolic and mitochondrial markers, in resting human PLTs isolated from a cohort of healthy donors is provided.