Attractive and repulsive residue fragments at the interface of SARS-CoV-2 and hACE2

The initial stages of SARS-CoV-2 coronavirus attachment to human cells are mediated by non-covalent interactions of viral spike (S) protein receptor binding domains (S-RBD) with human ACE2 receptors (hACE2). Structural characterization techniques, such as X-ray crystallography (XRC) and cryoelectron microscopy (cryo-EM), previously identified SARS-CoV-2 spike protein conformations and their surface residues in contact with hACE2. However, recent quantum-biochemical calculations on the structurally related S-RBD of SARS-CoV-1 identified some contact-residue fragments as intrinsically attractive and others as repulsive. This indicates that not all surface residues are equally important for hACE2 attachment. Here, using similar quantum-biochemical methods, we report some four-residue fragments (i.e quartets) of the SARS-CoV-2 S-RBD as intrinsically attractive towards hACE2 and, therefore, directly promoting host–virus non-covalent binding. Other fragments are found to be repulsive although involved in intermolecular recognition. By evaluation of their respective intermolecular interaction energies we found two hACE2 fragments that include contact residues (ASP30, LYS31, HIS34) and (ASP38, TYR41, GLN42), respectively, behaving as important SARS-CoV-2 attractors. LYS353 also promotes viral binding via several mechanisms including dispersion van der Waals forces. Similarly, among others, three SARS-CoV-2 S-RBD fragments that include residues (GLN498, THR500, ASN501), (GLU484, PHE486, ASN487) and (LYS417), respectively, were identified as hACE2 attractors. In addition, key hACE2 quartets identified as weakly-repulsive towards the S-RBD of SARS-CoV-1 were found strongly attractive towards SARS-CoV-2 explaining, in part, the stronger binding affinity of hACE2 towards the latter coronavirus. These findings may guide the development of synthetic antibodies or identify potential viral epitopes.

An expanded halogen bonding scale using astatine

As a non-covalent interaction, halogen bonding is now acknowledged to be useful in all fields where the control of intermolecular recognition plays a pivotal role. Halogen-bond basicity scales allow to...

Context contribution to the intermolecular recognition of human ACE2-derived peptides by SARS-CoV-2 spike protein: implications for improving the peptide affinity but not altering the peptide specificity by optimizing indirect readout

Disrupting the intermolecular interaction of SARS-CoV-2 S protein with its cell surface receptor hACE2 is a therapeutic strategy against COVID-19. The protein context plays an essential role in hACE α1-helix recognition by viral S protein.

Chiral Recognition of Hexahelicene on a Surface via the Forming of Asymmetric Heterochiral Trimers

Chiral recognition among helical molecules is of essential importance in many chemical and biochemical processes. The complexity necessitates investigating manageable model systems for unveiling the fundamental principles of chiral recognition at the molecular level. Here, we reported chiral recognition in the self-assembly of enantiopure and racemic hexahelicene on a Au(111) surface. Combing scanning tunneling microscopy (STM) and atomic force microscopy (AFM) measurements, the asymmetric heterochiral trimers were observed as a new type of building block in racemic helicene self-assembly on Au(111). The intermolecular recognition of the heterochiral trimer was investigated upon manual separation so that the absolute configuration of each helicene molecule was unambiguously determined one by one, thus confirming that the trimer was “2+1” in handedness. These heterochiral trimers showed strong stability upon different coverages, which was also supported by theoretical calculations. Our results provide valuable insights for understanding the intermolecular recognition of helical molecules.

Playing supramolecular dominoes with light: building and breaking a photoreversible G-quadruplex made from guanosine, boric acid and an azobenzene

Addition of an azo dye triggers a cascade of photoreversible intermolecular recognition processes in a mixture of simple guanosine derivatives.

Axially Chiral Shape-Persistent Encapsulating Agents

In this review is presented the results of investigations during the last two decades on molecular recognition processes, mainly chiral host–guest systems insofar as they deal with intermolecular recognition events. Attention is devoted to those systems involving chiral hosts whose chirality does not arise from the presence of a chiral center and that possess a defined cavity to accommodate guests. Thus, the scope of this short review is restricted to chiral containers in which size, shape, and functionality are critical aspects, while those examples involving chirality transfer processes are excluded. The systems covered are those with axial chirality, including helical chirality, in which the chirality, that can be inherent or induced by steric interactions, originates from the 3D helical array of substituents. More specifically, the focus is on both macrocycles that bear open cavities and molecular cages with more enclosed voids.1 Introduction2 Encapsulating Agents: Macrocycles3 Encapsulating Agents: Molecular Cages4 Conclusions