complexity domain  (Genovis Inc)

Journal: iScience

Article Title: A combinatorial and computational Tandem approach towards a universal therapeutics against ACE2-mediated coronavirus infections

doi: 10.1016/j.isci.2025.112687

Figure Lengend Snippet: Native human ACE2–SARS-CoV/SARS-CoV-2 complex (A) The extracellular domain of ACE2 shown in dark gray is bound to the receptor binding domain of SARS-CoV-2 (light gray). Image created from PDB: 6M0J . The complex interface is outlined. (B) (Top) The interface in detail. ACE2/SARS-CoV residues are colored red and pink, respectively, while ACE2/SARS-CoV-2 residues are presented in blue and light blue. Image was created from PDB: 2AJF and 6M0J . Key residues that factor prominently in in silico SSM analysis are highlighted with bold text. (Bottom left) The native interactions of ACE2 with SARS-CoV RBD consist of weak hydrophobic interactions between ACE2 T27 and RBD L443, F460, and Y475 and several hydrogen bonds formed between the C-terminus of ACE2’s N-terminal helix and the RBD. (Bottom right) Native interactions of ACE2 bound to SARS-CoV-2 RBD are largely similar to those of SARS-CoV albeit with a greater number and distribution of hydrogen bonds and slightly more satisfied hydrophobic interactions between ACE2 T27 and RBD F456, Y473, and Y489.

Article Snippet: Structure of SARS coronavirus spike receptor-binding domain complexed with its receptor , Protein DataBank , PDB: 2AJF.

Techniques: Binding Assay, In Silico

Journal: iScience

Article Title: A combinatorial and computational Tandem approach towards a universal therapeutics against ACE2-mediated coronavirus infections

doi: 10.1016/j.isci.2025.112687

Figure Lengend Snippet: Kinetic binding of ACE2 single mutants Binding and dissociation of ACE2 mutant variants to and from immobilized SARS-CoV and SARS-CoV-2 RBDs by BLI. The supernatant of ExpiCHOs transiently expressing ACE2-Fc variants was used directly for the binding test. Selected variants for further study were shown in solid line, and the top variants from the in silico approach were shown in dashed lines. No accurate KD for crude supernatant test as the protein concentration is unknown. See also .

Article Snippet: Structure of SARS coronavirus spike receptor-binding domain complexed with its receptor , Protein DataBank , PDB: 2AJF.

Techniques: Binding Assay, Mutagenesis, Expressing, In Silico, Protein Concentration

Journal: iScience

Article Title: A combinatorial and computational Tandem approach towards a universal therapeutics against ACE2-mediated coronavirus infections

doi: 10.1016/j.isci.2025.112687

Figure Lengend Snippet: ACE2 triple mutant affinity measurement against MBP-SARS-CoV RBD and MBP-SARS-CoV-2 RBD Binding affinity of ACE2-Fc triple mutant and wild-type ACE2 to SARS-CoV and SARS-CoV-2 spike RBD proteins was measured by BLI assay. All the variants and the wild-type (WT) ACE2 shown here have R273Q/H505L mutation in ACE2. Immobilized ACE2-Fc binding to the RBDs was tested using a range of MBP-RBD concentrations from 200 nM to 3,125 nM (in 2-fold dilution).

Article Snippet: Structure of SARS coronavirus spike receptor-binding domain complexed with its receptor , Protein DataBank , PDB: 2AJF.

Techniques: Mutagenesis, Binding Assay

Journal: iScience

Article Title: A combinatorial and computational Tandem approach towards a universal therapeutics against ACE2-mediated coronavirus infections

doi: 10.1016/j.isci.2025.112687

Figure Lengend Snippet: ACE2/RBD interaction surface (A) A space-filling view of native ACE2 interactions with SARS-COV-2 RBD. WT ACE2 residues T27/K31/H34 are shown in dark gray, and the SARS-CoV-2 RBD residues are shown in light gray. (B) Interactions of the YHA triple mutants (residues shown in green) with the SARS-CoV-2 RBD. The red and blue dots represent oxygen and nitrogen, respectively.

Article Snippet: Structure of SARS coronavirus spike receptor-binding domain complexed with its receptor , Protein DataBank , PDB: 2AJF.

Techniques:

Journal: iScience

Article Title: A combinatorial and computational Tandem approach towards a universal therapeutics against ACE2-mediated coronavirus infections

doi: 10.1016/j.isci.2025.112687

Figure Lengend Snippet: Neutralization of SARS-CoV and SARS-CoV-2 pseudoviruses (A and B) Infection of CHO-ACE2 cells by SARS-CoVs pseudoviruses were determined in the presence of ACE2 variants. Luciferase activities in the CHO-ACE2 cells were measured, and the percent neutralization was calculated. The neutralization curves of some test results are shown in (A) to exhibit the dose-dependent neutralization of ACE2-Fc variants. Data are presented as mean ± SD in duplicates and are representative of two independent experiments. The IC50 was calculated by a variable slope four-parameter non-linear regression model using Graphpad PRISM 7 Software. Average IC50 of ACE2 mutant variants against WT SARS-CoV, WT SARS-CoV-2, and 31 variants of SARS-CoV-2 from two independent experiments are shown in (B). The dot line showed the limitation of detection (no neutralization). (C) Neutralization of pseudoviruses representing various recent Omicron lineage variants of SARS-CoV-2. Average IC50 of ACE2-WT and ACE2-YHA are shown against WT SARS-CoV-2 and 14 Omicron variants from two independent experiments. All the ACE2 variants and ACE2-WT shown here have R273Q/H505L mutation in ACE2.

Article Snippet: Structure of SARS coronavirus spike receptor-binding domain complexed with its receptor , Protein DataBank , PDB: 2AJF.

Techniques: Neutralization, Infection, Luciferase, Software, Mutagenesis

Journal: iScience

Article Title: A combinatorial and computational Tandem approach towards a universal therapeutics against ACE2-mediated coronavirus infections

doi: 10.1016/j.isci.2025.112687

Figure Lengend Snippet: Engineered ACE2-YHA decoy protects human airway epithelium from infection with antigenically distant SARS-CoV-2 viruses MucilAir nasal HAE were infected with B.1.617.2 (MOI 0.01) or BA.5 (MOI 0.001) SARS-CoV-2 viruses previously preincubated for 60 min with 250 ng/mL of ACE2-WT or ACE2-YHA decoys. (A and B) Relative apical viral titers as determined by RT-qPCR and expressed in fold change of nsp14 copies compared to the infected untreated control (CTL, dotted line). (C and D) Transepithelial electrical resistance (TEER) between the apical and basal poles of the HAE. ∗ p < 0.05, ∗∗ p < 0.01, and ∗∗∗ p < 0.001 indicate statistically significant differences in viral load between groups, determined by two-way analysis of variance (ANOVA) with Bonferroni post-test, performed using Graphpad PRISM 7 Software. Data are presented as median with range, based on four biological replicates per treatment condition ( n = 4) and three replicates for the mock controls ( n = 3). Each replicate corresponds to a single individual Transwell insert.

Article Snippet: Structure of SARS coronavirus spike receptor-binding domain complexed with its receptor , Protein DataBank , PDB: 2AJF.

Techniques: Infection, Quantitative RT-PCR, Control, Software