An Approach for Zika Virus Inhibition Using Homology Structure of the Envelope Protein
Language English Country Switzerland Media print
Document type Journal Article
PubMed
27683255
DOI
10.1007/s12033-016-9979-1
PII: 10.1007/s12033-016-9979-1
Knihovny.cz E-resources
- Keywords
- Drug discovery, Druggability, Homology model, Zika virus,
- MeSH
- Antiviral Agents chemistry pharmacology MeSH
- Chlorocebus aethiops MeSH
- Small Molecule Libraries chemistry pharmacology MeSH
- Models, Molecular MeSH
- Computer Simulation MeSH
- Polysaccharides metabolism MeSH
- Viral Envelope Proteins antagonists & inhibitors chemistry MeSH
- Structural Homology, Protein MeSH
- Binding Sites MeSH
- Vero Cells MeSH
- Viral Load drug effects MeSH
- Zika Virus drug effects metabolism MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antiviral Agents MeSH
- Small Molecule Libraries MeSH
- Polysaccharides MeSH
- Viral Envelope Proteins MeSH
To find an effective drug for Zika virus, it is important to understand how numerous proteins which are critical for the virus' structure and function interact with their counterparts. One approach to inhibiting the flavivirus is to deter its ability to bind onto glycoproteins; however, the crystal structures of envelope proteins of the ever-evolving viral strains that decipher glycosidic or drug-molecular interactions are not always available. To fill this gap, we are reporting a holistic, simulation-based approach to predict compounds that will inhibit ligand binding onto a structurally unresolved protein, in this case the Zika virus envelope protein (ZVEP), by developing a three-dimensional general structure and analyzing sites at which ligands and small drug-like molecules interact. By examining how glycan molecules and small-molecule probes interact with a freshly resolved ZVEP homology model, we report the susceptibility of ZVEP to inhibition via two small molecules, ZINC33683341 and ZINC49605556-by preferentially binding onto the primary receptor responsible for the virus' virulence. Antiviral activity was confirmed when ZINC33683341 was tested in cell culture. We anticipate the results to be a starting point for drug discovery targeting Zika virus and other emerging pathogens.
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