Strengthening CoViD-19 therapy via combinations of RAS modulators.

Evidence has accumulated that the pathology of CoViD-19 is strongly related to the renin-angiotensin system (RAS). The blockage of the angiotensin converting enzyme 2 (ACE2) by the SARS-CoV-2 virus leads to downstream consequences such as increased vascular tone, extensive fibrosis and pronounced immune reactions. Different approaches to tackle the adverse viral effects by compensating the lost ACE2 function have been suggested.

Phyllostictine A: total synthesis, structural verification and determination of substructure responsible for plant growth inhibition.

The first total synthesis of phyllostictine A (PA) is reported, which confirms the structure of this fungal metabolite and its (6S,7R,8S)-stereochemistry. Both synthetic PA and an analogue containing the 5-methylene-1,5-dihydro-2H-pyrrol-2-one nucleus exhibit μM inhibitory activity in root growth assays against Arabidopsis thaliana, indicating that this heterocyclic subunit is key to the herbicidal activity of the natural product.

Tomographic docking suggests the mechanism of auxin receptor TIR1 selectivity.

We study the binding of plant hormone IAA on its receptor TIR1, introducing a novel computational method that we call tomographic docking and that accounts for interactions occurring along the depth of the binding pocket. Our results suggest that selectivity is related to constraints that potential ligands encounter on their way from the surface of the protein to their final position at the pocket bottom. Tomographic docking helps develop specific hypotheses about ligand binding, distinguishing binders from non-binders, and suggests that binding is a three-step mechanism, consisting of engagement with a niche in the back wall of the pocket, interaction with a molecular filter which allows or precludes further descent of ligands, and binding on the pocket base.

Free heme and the polymerization of sickle cell hemoglobin.

In search of novel control parameters for the polymerization of sickle cell hemoglobin (HbS), the primary pathogenic event of sickle cell anemia, we explore the role of free heme, which may be excessively released in sickle erythrocytes. We show that the concentration of free heme in HbS solutions typically used in the laboratory is 0.02-0.

Free heme in micromolar amounts enhances the attraction between sickle cell hemoglobin molecules.

We probe the role of free heme in the interactions between sickle cell hemoglobin (HbS) molecules in simulated physiological solutions: polymerization of deoxy-HbS is the primary pathogenic event of sickle cell anemia, and HbS releases heme after autoxidation more readily than normal adult hemoglobin. We characterize these interactions in terms of osmotic virial coefficients, which we determine by static light scattering. We analyze the results in the heme-hemoglobin system using the Kirkwood-Goldberg model.

Viscoelasticity in homogeneous protein solutions.

We probe the transport properties in protein solutions stable with respect to any, solid or liquid, phase separation as a step in the understanding of transport in the cytosol of live cells. We determine the mean-squared displacement of probe particles in the time range 10;{-3}-10 s in solutions of a model protein. The tested solutions exhibit significant elasticity at high frequencies, while at low frequencies, they are purely viscous.