S glycoprotein diversity of the Omicron variant

On the backdrop of ongoing Delta variant infection and vaccine-induced immunity, the emergence of the new Variant of Concern, the Omicron, has again fuelled the fears of COVID-19 around the world. Currently, very little information is available about the S glycoprotein mutations, transmissibility, severity, and immune evasion behaviour of the Omicron variant. In the present study, we have performed a comprehensive analysis of the S glycoprotein mutations of 309 strains of the Omicron variant and also discussed the probable effects of observed mutations on several aspects of virus biology based on known available knowledge of mutational effects on S glycoprotein structure, function, and immune evasion characteristics.

Regional Variant Analysis of Spike Glycoprotein Mutations of SARS-CoV-2 and Its Implications in COVID-19 Pandemic Control

Mutations in the spike glycoprotein have various impacts on the receptor binding, antibody in-teraction, and host range of SARS-CoV-2. As the interaction of spike glycoprotein with the human ACE2 receptor is the entry point of SARS-CoV-2 in human cells, mutations in the spike protein it-self contain numerous impacts on the pandemic. Here, we analysed all the mutations in the spike glycoprotein from123 strains isolated from Kerala, India. We also predicted the possible struc-tural relevance of the unique mutations based on topological analysis of the residue interaction network of the spike glycoprotein structure.

Example of Steady-State Electric-Current Modeling of a Complicated Cellular Topology with Boundary Element Fast Multipole Method

In this study, we demonstrate the ability of the boundary element fast multipole method (BEM-FMM) to perform electrical modeling of a rather complicated microbiological surface topology in a reasonable amount of time. As an example, we consider a Computer Aided Design (CAD)-based SARS-CoV-2 spike glycoprotein structure. This structure is crucial to the mechanism by which the coronavirus attaches to a target object. Only classic DC steady-state modeling has been performed, in an isotropic continuous medium.

Glycoinformatics approach for identifying target positions to inhibit initial binding of SARS-CoV-2 S1 protein to the host cell

COVID-19 outbreak is still threatening the public health. Therefore, in the middle of the pandemic, all kind of knowledge on SARS-CoV-2 may help us to find the solution. Determining the 3D structures of the proteins involved in host-pathogen interactions are of great importance in the fight against infection. Besides, post-translational modifications of the protein on 3D structure should be revealed in order to understand the protein function since these modifications are responsible for the host-pathogen interaction. Based on these, we predicted O-glycosylation and phosphorylation positions using full amino acid sequence of S1 protein. Candidate positions were further analyzed with enzyme binding activity, solvent accessibility, surface area parameters and the positions determined with high accuracy rate were used to design full 3D glycoprotein structure of the S1 protein using carbohydrate force field. In addition, the interaction between the C-type lectin CD209L and α-mannose residues was examined and carbohydrate recognition positions were predicted. We suggest these positions as a potential target for the inhibition of the initial binding of SARS-CoV-2 S1 protein to the host cell.

Darunavir Disrupts Critical Nodes in Metastable 2019-nCoV-RBD/ACE-2 Complex

The transnational spread of coronavirus (2019-nCoV) first detected in Wuhan is causing global panic; thus, accelerated research into clinical intervention is of high necessity. The spike glycoprotein structure has been resolved, and its affinity to human angiotensin-converting enzyme 2 (ACE-2) has been experimentally validated. Here, using computational methods, a metastable conformation of 2019-nCoV-RBD/ACE-2 complex has been revealed and FDA-database of approved drugs have been docked into the interface. Darunavir has been discovered as high ligand affinity candidate capable of disrupting communication between 2019-nCoV-RBD and ACE-2. Darunavir, in addition to its previously known anti-HIV protease inhibitor is now repurposeable for the treatment 2019-nCoV disease acting via disruption of cellular recognition, binding and invasion.

Making glycoproteins a little bit sweeter withPDB-REDO

Glycosylation is one of the most common forms of protein post-translational modification, but is also the most complex. Dealing with glycoproteins in structure model building, refinement, validation and PDB deposition is more error-prone than dealing with nonglycosylated proteins owing to limitations of the experimental data and available software tools. Also, experimentalists are typically less experienced in dealing with carbohydrate residues than with amino-acid residues. The results of the reannotation and re-refinement byPDB-REDOof 8114 glycoprotein structure models from the Protein Data Bank are analyzed. The positive aspects of 3620 reannotations and subsequent refinement, as well as the remaining challenges to obtaining consistently high-quality carbohydrate models, are discussed.