Screening of Potent Inhibitor of H1N1 Influenza NS1 CPSF30 Binding Pocket by Molecular Docking


The swine flu, H1N1 virus was outbroken in Mexico and the United States in April 2009 and then rapidly spread worldwide. The World Health Organization declared that the outbreak of influenza is caused by a new subtype of influenza H1N1 influenza virus. And researchers have isolated some oseltamivir resistance strains in 2009 swine flu which makes the imminency of research and development of new anti influenza drug. The CPSF30 binding pocket of effector domain in NS1 protein is very important in the replication of influanza A virus and is a new attractive anti flu drug target. But up to now there is no antiviral drug target this pocket. Here we employ molecular docking to screening of about 200,000 compounds. We find four novel compounds with high binding energy. Binding comformation analysis revealed that these small molecules can interact with the binding pocket by some strong hydrophobic interaction. This study find some novel small molecules can be used as lead compounds in the development of new antiinfluenza drug based on CPSF30 pocket.

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L. Zhang, J. Zhao, G. Ding, X. Li and H. Liu, "Screening of Potent Inhibitor of H1N1 Influenza NS1 CPSF30 Binding Pocket by Molecular Docking," Advances in Infectious Diseases, Vol. 2 No. 4, 2012, pp. 92-96. doi: 10.4236/aid.2012.24015.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] A. H. Reid, J. K. Taubenberger and T. G. Fanning, “The 1918 Spanish influenza: Integrating History and Biology,” Microbes and Infection, Vol. 3, No. 1, 2001, pp. 81-87. doi:10.1016/S1286-4579(00)01351-4
[2] H. Nicholls, “Pandemic Influenza: The Inside Story,” PLoS Biology, Vol. 4, No. 2, 2006, p. e50.
[3] WHO, “Pandemic (H1N1) 2009—Update 112,” 2010.
[4] B. G. Hale, R. E. Randall, J. Ortin and D. Jackson, “The Multifunctional NS1 Protein of Influenza A Viruses,” Journal of General Virology, Vol. 89, No. 10, 2008, pp. 2359-2376. doi:10.1099/vir.0.2008/004606-0
[5] R. M. Krug, W. Yuan, D. L. Noah and A. G. Latham, “Intracellular Warfare between Human Influenza Viruses and Human Cells: The Roles of the Viral NS1 Protein,” Virology, Vol. 309, No. 2, 2003, pp. 181-189. doi:10.1016/S0042-6822(03)00119-3
[6] J. Y. Min and R. M. Krug, “The Primary Function of RNA Binding by the Influenza A Virus NS1 Protein in Infected Cells: Inhibiting the 2 - 5 Oligo (A) Synthetase/ RNase L Pathway,” Proceedings of the National Academic of Sciences of the United States of America, Vol. 103, No. 8, 2006, pp. 7100-7105.
[7] Y. K. Shin, Q. Liu, S. K. Tikoo, L. A. Babiuk and Y. Zhou, “Influenza A Virus NS1 Protein Activates the Phosphatidylinositol 3-Kinase (PI3K)/Akt Pathway by Direct Interaction with the P85 Subunit of PI3K,” Journal of General Virology, Vol. 88, No. 1, 2007, pp. 13-18. doi:10.1099/vir.0.82419-0
[8] J. Y. Min, S. Li, G. C. Sen and R. M. Krug, “A Site on the Influenza A Virus NS1 Protein Mediates Both Inhibition of PKR Activation and Temporal Regulation of Viral RNA Synthesis,” Virology, Vol. 363, No. 1, 2007, pp. 236-243. doi:10.1016/j.virol.2007.01.038
[9] O. G. Engelhardt and E. Fodor, “Functional Association between Viral and Cellular Transcription during Influenza Virus Infection,” Reviews in Medical Virology, Vol. 16, No. 5, 2006, pp. 329-345. doi:10.1002/rmv.512
[10] D. L. Noah, K. Y. Twu and R. M. Krug, “Cellular Antiviral Responses against Influenza A Virus Are Countered at the Post Transcriptional Level by the Viral NS1A Protein via Its Binding to a Cellular Protein Required for the 3’End Processing of Cellular Pre-mRNAS,” Virology, Vol. 307, No. 2, 2003, pp. 386-395. doi:10.1016/S0042-6822(02)00127-7
[11] K. Y. Twu, D. L. Noah, P. Rao, R. L. Kuo and R. M. Krug, “The CPSF30 Binding Site on the NS1A Protein of Influenza A Virus Is a Potential Antiviral Target,” Journal of Virology, Vol. 80, No. 8, 2006, pp. 3957-3965. doi:10.1128/JVI.80.8.3957-3965.2006
[12] K. Das, et al., “Structural Basis for Suppression of a Host Antiviral Response by Influenza A Virus,” Proceedings of the National Academy of Sciences, Vol. 105, No. 35, 2008, pp. 13093-13098. doi:10.1073/pnas.0805213105
[13] D. Basu, et al., “Novel Influenza Virus NS1 Antagonists Block Replication and Restore Innate Immune Function,” Journal of Virology, Vol. 83, No. 4, 2008, pp. 1881-1891. doi:10.1128/JVI.01805-08
[14] M. P. Walkiewicz, D. Basu, J. J. Jablonski, H. M. Geysen and D. A. Engel, “Novel Inhibitor of Influenza Non-Structural Protein 1 Blocks Multi-Cycle Replication in an RNase L-Dependent Manner,” Journal of General Virology, Vol. 92, No. 1, 2011, pp. 60-70. doi:10.1099/vir.0.025015-0
[15] R. Guha, et al., “The Blue Obelisk Interoperability in Chemical Informatics,” Journal of Chemical Information and Modeling, Vol. 46, No. 3, 2006, pp. 991-998. doi:10.1021/ci050400b
[16] T. Cheng, et al., “Computation of Octanol-Water Partition Coefficients by Guiding an Additive Model with Knowledge,” Journal of Chemical Information and Modeling, Vol. 47, No. 6, 2007, pp. 2140-2148. doi:10.1021/ci700257y
[17] C. A. Lipinski, “Drug-Like Properties and the Causes of Poor Solubility and Poor Permeability,” Journal of Pharmacological and Toxicological Methods, Vol. 44, No. 1, 2000, pp. 235-249. doi:10.1016/S1056-8719(00)00107-6
[18] H. Ai, et al., “Discovery of Novel Influenza Inhibitors Targeting the Interaction of dsRNA with the NS1 Protein by Structure-Based Virtual Screening,” International Journal of Bioinformatics Research and Applications, Vol. 6, No. 5, 2010, pp. 449-460. doi:10.1504/IJBRA.2010.037985
[19] G. M. Morris, et al., “AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility,” Journal of Computational Chemistry, Vol. 30, No. 16, 2009, pp. 2785-2791. doi:10.1002/jcc.21256
[20] H. Park, J. Lee and S. Lee, “Critical Assessment of the Automated AutoDock as a New Docking Tool for Virtual Screening,” Proteins: Structure, Function, and Bioinformatics, Vol. 65, No. 3, 2006, pp. 549-554. doi:10.1002/prot.21183
[21] M. Larkin, et al., “Clustal W and Clustal X Version 2.0,” Bioinformatics, Vol. 23, No. 21, 2007, pp. 2947-2948. doi:10.1093/bioinformatics/btm404
[22] A. C. Wallace, R. A. Laskowski and J. M. Thornton, “LIGPLOT: A Program to Generate Schematic Diagrams of Protein-Ligand Interactions,” Protein Engineering, Vol. 8, No. 2, 1995, pp. 127. doi:10.1093/protein/8.2.127
[23] P. Rice, I. Longden and A. Bleasby, “EMBOSS: The European Molecular Biology Open Software Suite,” Trends in Genetics, Vol. 16, No. 6, 2000, pp. 276-277. doi:10.1016/S0168-9525(00)02024-2
[24] W. L. DeLano, “The PyMOL Molecular Graphics System,” DeLano Scientific LLC, Palo Alto, 2002.

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