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An Immune complex formation is mediated through intermolecular interactions between proteins and antigens. In the present study, in silico methods were used to locate, identify and provide valuable structural and energetic information that describes the dominant and energetically stabilising interactions found at the epitope-paratope interface of selected human antibodies, isolated from convalescent COVID-19 patients. These antibodies are directed toward the SARS-CoV-2 receptor-binding domain (RBD, i.e. residues 333–526). The analyzed immune complexes have shown strong in vitro neutralising activity against SARS-CoV-2 infection by targeting the receptor-binding motif (RBM, i.e. residues 437–508) within the viral SARS-CoV-2 spike RBD. Our data shows that residues Tyr449, Leu455, Phe456, Ala475, Phe486, Gln493, Gln498, Asn501, Gly502 and Tyr505 exhibit strong epitope capability. On another hand, the analyzed paratopes show a large repertoire of residues to recognise RBM epitopes by both the VH and VL chains within complementary determining regions (CDR), which would make it difficult to bind RBM to the human ACE2 cell receptor by residue interactions competition. Undoubtedly, our findings provide valuable structural and energetic information to those previously obtained through experimental crystallographic studies, and provides new insights about the binding interface that could provide a structural basis for rational epitope-based vaccinology.

We report here two new small-size peptides acting as modulators of the β-site APP cleaving enzyme 1 (BACE1) exosite. Ac-YPYFDPL-NH2 and Ac-YPYDIPL-NH2 displayed a moderate but significant inhibitory effect on BACE1. These peptides were obtained from a molecular modeling study. By combining MD simulations with ab initio and DFT calculations, a simple and generally applicable procedure to evaluate the binding energies of small-size peptides interacting with the exosite of the BACE1 is reported here. The structural aspects obtained for the different complexes were analyzed providing a clear picture about the binding interactions of these peptides. These interactions have been investigated within the framework of the density functional theory and the quantum theory of atoms in molecules using a reduced model. Although the approach used here was traditionally applied to the study of noncovalent interactions in small molecules complexes in gas phase, we show, through in this work, that this methodology is also a very powerful tool for the study of biomolecular complexes, providing a very detailed description of the binding event of peptides modulators at the exosite of BACE1. Fil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina Fil: Angelina, Emilio Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gyebrovszki, Andrea. University of Szeged. Department of Medical Chemistry; Hungría Fil: Fülöp, Livia. University of Szeged. Department of Medical Chemistry; Hungría Fil: Peruchena, Nelida Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina Fil: Baldoni, Hector Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis ; Argentina Fil: Penke, Botond. University of Szeged. Department of Medical Chemistry; Hungría Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina

The molecular mechanism of recognition of amyloid-beta (Aβ) peptide isoforms by bapineuzumab was studied using a quantum mechanics and molecular mechanics (QM/MM) method. In this work, geometric optimisations were performed using the ONIOM2 scheme (at B3LYP/6-31G(d) amber)EE level) on the paratope of bapineuzumab together with the different forms of Aβ peptide (AβWT and AβN3(pE)). A comprehensive study of the interactions was also performed through Quantum Theory of Atoms in Molecules (QTAIM). This allowed us to obtain a deep understanding of how this antibody interacts with the amino acids of the Aβ peptides. The description on the interactions between bapineuzumab and the different forms of Aβ peptides allow us to understand why the peptides that lack the two first residues (Asp1 and Ala2) and begin with a pyroglutamate residue present low affinity for bapineuzumab. This basic structural information is useful for a deeper understanding about the scope and limitations of bapineuzumab as a therapeutic agent for the AD. Fil: Gutierrez, Lucas Joel. Universidad Nacional del Nordeste; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Luis; Argentina Fil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste; Argentina Fil: Enriz, Ricardo Daniel. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

3α-Hydroxycarvotagenone and its epimer 3β-hydroxy carvotagenone were isolated as a minor mixture and its structure determined by spectral means. The mixture was then used in cytoprotection experiments. The mixture, in spite of possessing a Michael acceptor, did not show cytoprotective activity. The lack of activity was attributed to the presence of a -OH group next to the β-carbon of the Michael acceptor. This -OH group could react in a intramolecular way yielding an epoxide which would produce the inhibition of the Michael acceptor. In order to confirm this, the mixture was acetylated and the mixture of acetates used in our cytoprotection experiments. The mixture of acetates showed a moderate but significant cytoprotection probing the existence of some kind of stereoelectronic interaction between the acceptor and the nucleophile.