The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.

Design and characterization of MP0250, a tri-specific anti-HGF/anti-VEGF DARPin® drug candidate.

MP0250 is a multi-domain drug candidate currently being tested in clinical trials for the treatment of cancer. It comprises one anti-vascular endothelial growth factor-A (VEGF-A), one anti-hepatocyte growth factor (HGF), and two anti-human serum albumin (HSA) DARPin® domains within a single polypeptide chain. While there is first clinical validation of a single-domain DARPin® drug candidate, little is known about DARPin® drug candidates comprising multiple domains.

A hypothesis for the origin and pathogenesis of rheumatoid diseases.

It is well established that a correlation exists between rheumatoid arthritis (RA) and microbial damage. Material analyses have suggested that bacteria may be causative agents. This study was undertaken to further characterize the microbial agent responsible for pathogenesis of RA.

Membrane effects of chloride substitutes in guinea pig gallbladder epithelial cells.

Differences in the responses of guinea pig gallbladder epithelial cells to replacement of luminal Cl- with either isethionate (I), gluconate (G), sulfate (S), or cyclamate (C) were investigated in vitro using intracellular microelectrode techniques. In prostaglandin E1 (PGE1)-treated tissues (10(-6) M, serosal side), where electrodiffusive apical membrane Cl- permeability (PCla) is high, replacement of luminal Cl- caused transient membrane depolarizations of similar magnitudes but different times to peak (C greater than G = S greater than I). The subsequent shifts in membrane voltages were, at steady state, straight correlated with the concomitant increases in apparent ratio of apical to basolateral membrane resistances (Ra/Rb).

Application of chloride-selective microelectrodes to renal test dyes and other food or cosmetic dyes.

The measurement of chloride activity was studied with Cl- -sensitive ion-exchanger microelectrodes (ISE) in calibrated test solutions stained with commonly used renal test dyes (e.g. Lissamine green SF) or other food or cosmetic dyes.