Efficacy of the combination of monoclonal antibodies against the SARS-CoV-2 Beta and Delta variants.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the biggest healthcare issue worldwide. This study aimed to develop a monoclonal antibody against SARS-CoV-2 from B cells of recovered COVID-19 patients, which might have beneficial therapeutic purposes for COVID-19 patients. We successfully generated human monoclonal antibodies (hmAbs) against the receptor binding domain (RBD) protein of SARS-CoV-2 using developed hybridoma technology.

DutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously.

We report the development of a platform of dual targeting Fab (DutaFab) molecules, which comprise two spatially separated and independent binding sites within the human antibody CDR loops: the so-called H-side paratope encompassing HCDR1, HCDR3 and LCDR2, and the L-side paratope encompassing LCDR1, LCDR3 and HCDR2. Both paratopes can be independently selected and combined into the desired bispecific DutaFabs in a modular manner. X-ray crystal structures illustrate that DutaFabs are able to bind two target molecules simultaneously at the same Fv region comprising a VH-VL heterodimer.

Rational design of balanced dual-targeting antibiotics with limited resistance.

Antibiotics that inhibit multiple bacterial targets offer a promising therapeutic strategy against resistance evolution, but developing such antibiotics is challenging. Here we demonstrate that a rational design of balanced multitargeting antibiotics is feasible by using a medicinal chemistry workflow. The resultant lead compounds, ULD1 and ULD2, belonging to a novel chemical class, almost equipotently inhibit bacterial DNA gyrase and topoisomerase IV complexes and interact with multiple evolutionary conserved amino acids in the ATP-binding pockets of their target proteins.

Synthesis of branched and linear 1,4-linked galactan oligosaccharides.

We report the synthesis of linear and branched (1→4)-d-galactans. Four tetrasaccharides and one pentasaccharide were accessed by adopting a procedure of regioselective ring opening of a 4,6-O-naphthylidene protecting group followed by glycosylation using phenyl thioglycoside donors. The binding of the linear pentasaccharide with galectin-3 is also investigated by the determination of a co-crystal structure.