Discovery of a Non-Peptidic Inhibitor of West Nile Virus NS3 Protease by High-Throughput Docking
2009

Discovery of a Non-Peptidic Inhibitor of West Nile Virus NS3 Protease

Sample size: 22 publication Evidence: moderate

Author Information

Author(s): Ekonomiuk Dariusz, Su Xun-Cheng, Ozawa Kiyoshi, Bodenreider Christophe, Lim Siew Pheng, Yin Zheng, Keller Thomas H., Beer David, Patel Viral, Otting Gottfried, Caflisch Amedeo, Huang Danzhi

Primary Institution: University of Zürich

Hypothesis

Can a small-molecule inhibitor be identified for the West Nile virus NS3 protease using high-throughput docking?

Conclusion

The identified inhibitor has good potential as a lead compound for further development against West Nile virus infections.

Supporting Evidence

  • The inhibitor showed a ligand efficiency of 0.33 kcal/mol per non-hydrogen atom.
  • Six out of 22 compounds tested showed specific affinity to the WNV protease.
  • The binding affinity of the inhibitor was confirmed by NMR spectroscopy.

Takeaway

Scientists found a small molecule that can stop a virus from making copies of itself, which could help in creating new medicines.

Methodology

The study used high-throughput docking of about 12,000 compounds and validated the findings with NMR spectroscopy and enzymatic assays.

Limitations

The binding affinity of the inhibitor is relatively low, and further optimization is needed.

Digital Object Identifier (DOI)

10.1371/journal.pntd.0000356

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