The role of S477N mutation in the molecular behavior of SARS-CoV-2 spike protein: An in-silico perspective.

The attachment of SARA-CoV-2 happens between ACE2 and the receptor binding domain (RBD) on the spike protein. Mutations in this domain can affect the binding affinity of the spike protein for ACE2. S477N, one of the most common mutations reported in the recent variants, is located in the RBD. Today's computational approaches in biology, especially during the SARS-CoV-2 pandemic, assist researchers in predicting a protein's behavior in contact with other proteins in more detail. In this study, we investigated the interactions of the S477N-hACE2 in silico to find the impact of this mutation on its binding affinity for ACE2 and immunity responses using dynamics simulation, protein-protein docking, and immunoinformatics methods. Our computational analysis revealed an increased binding affinity of N477 for ACE2. Four new hydrogen and hydrophobic bonds in the mutant RBD-ACE2 were formed (with S19 and Q24 of ACE2), which do not exist in the wild type. Also, the protein spike structure in this mutation was associated with an increase in stabilization and a decrease in its fluctuations at the atomic level. N477 mutation can be considered as the cause of increased escape from the immune system through MHC-II.

Binder design for targeting SARS-CoV-2 spike protein: An in silico perspective.

INTRODUCTION: The COVID-19 pandemic is now affecting all people around the world and getting worse. New antiviral medications are desperately needed other than the few approved medications that have shown no promising efficacy so far. METHODS: Here we report three blocking binders for targeting SARS-CoV-2 spike protein to block the interaction between the spike protein on the SARS-CoV-2 and the angiotensin-converting enzyme 2 (ACE2) receptors, responsible for viral homing into the alveolar epithelium type II cells (AECII). RESULTS: The design process is based on the collected natural scaffolds and using Rosetta interface for designing the binders. CONCLUSION: Based on the structural analysis, three binders were selected, and the results showed that they might be promising as new therapeutic targets for blocking COVID-19.

Designed proteins assemble antibodies into modular nanocages.

Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)-mediated apoptosis, angiopoietin-1 receptor (Tie2)-mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc-angiotensin-converting enzyme 2 (ACE2) fusion proteins.