ns5 protein  (Sino Biological)

Journal: Antiviral research

Article Title: Identification of pan-flavivirus compounds from drug repurposing.

doi: 10.1016/j.antiviral.2025.106205

Figure Lengend Snippet: Fig. 4. Resistance selection of compound 425. A) ZIKV was passaged for 14 times in presence or absence of increasing concentrations of compound 425, after each passage the treated and untreated viruses were titered. B) After 14 passages the viruses were tested for their susceptibility to 425 by plaque assay. Results are mean and SEM of three independent experiments. C) The list of mutations identified is shown. Positions are numbered according to sequence NC_035889. *Indicates mixed populations. D) The mutation in the N terminal of the NS3 helicase domain at the interface with NS5 RdRp is highlighted in the red circle.

Article Snippet: The stable cell line clones were validated by measuring the renilla luciferase expression, by immunofluorescence with an antibody specific for the WNV NS5 protein (PA5-111986 ThermoFisher Scientific) or by Western blot.

Techniques: Selection, Plaque Assay, Sequencing, Mutagenesis

Journal: Journal of enzyme inhibition and medicinal chemistry

Article Title: Identification of novel inhibitors of dengue viral NS5 RNA-dependent RNA polymerase through molecular docking, biological activity evaluation and molecular dynamics simulations.

doi: 10.1080/14756366.2025.2463006

Figure Lengend Snippet: Figure 1. Crystal structure of DENV-NS5 (PDB ID: 4V0R) and crystal structure of DENV-NS5 RdRp domain in complex with Compound 27 (PDB ID: 5K5M).

Article Snippet: here, for the allosteric site occupied by Compound 27, DeNV-Ns5 RdRp inhibitors were identified by using molecular docking, molecular dynamics (MD) simulation, cell-based assays, and density functional theory (DFt) calculations. the 1.6 million compounds in chemDiv and targetMol (Usa) database were screened by a structure-based virtual screening approach. the compounds with favourable interactions to the RdRp allosteric site and good aDMet properties were selected as candidates to inhibiting DeNV Ns5. according to the 50 ns MD simulation of binding free energy of the docking complex of candidates and the DeNV-Ns5 RdRp, the selected compounds was evaluated against DeNV-Ns5 cell-based assays. the 200 ns MD simulation and DFt calculations (B3lYP/6– 311++g(d,p)) were carried out on the candidates with higher or similar activity to that of reference Compound 27. the Figure 1. crystal structure of dEnV-ns5 (Pdb Id: 4V0r) and crystal structure of dEnV-ns5 rdrp domain in complex with Compound 27 (Pdb Id: 5K5m).

Techniques:

Journal: Journal of enzyme inhibition and medicinal chemistry

Article Title: Identification of novel inhibitors of dengue viral NS5 RNA-dependent RNA polymerase through molecular docking, biological activity evaluation and molecular dynamics simulations.

doi: 10.1080/14756366.2025.2463006

Figure Lengend Snippet: Figure 1. Crystal structure of DENV-NS5 (PDB ID: 4V0R) and crystal structure of DENV-NS5 RdRp domain in complex with Compound 27 (PDB ID: 5K5M).

Article Snippet: Firstly, the docking protocol has been validated by redocking original ligand (Compound 27) of crystal structure of DeNV-Ns5 to its binding domain. the docked pose is in agreement with the original pose, and the RsMD value of the two is 0.346 Å (Figure s1). after systematic molecular docking process, 200 candidates were retained from the 1.6 million compounds in the chemDiv and targetMol (Usa) database. their performance was evaluated using three key metrics: docking score, Uni-score Rescore, and MM/GBsa binding free energy.

Techniques: