Systematic approaches towards the development of host-directed antiviral therapeutics

International Journal of Molecular Sciences

Volumn 12, Issue 6, 2011, Pages 4027-4052

  Prussia, Andrew ^a   Thepchatri, Pahk ^a   Snyder, James P ^a   Plemper, Richard K ^b,c  

^a EMORY UNIVERSITY   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c CHILDREN'S HEALTHCARE OF ATLANTA   (United States)

Author keywords

Antiviral; Bioinformatics; Genome wide screening; HIV; Influenza virus; Pathway analysis; RNAi; siRNA; Target identification

Indexed keywords

IMATINIB; SMALL INTERFERING RNA; TAMOXIFEN; ANTIVIRUS AGENT;

ANTIVIRAL ACTIVITY; ANTIVIRAL THERAPY; BIOINFORMATICS; DATA BASE; DRUG CLASSIFICATION; DRUG DESIGN; DRUG RESEARCH; DRUG SCREENING; DRUG TARGETING; GENE TARGETING; GENETIC ASSOCIATION; GENETIC VARIABILITY; HOST DIRECTED ANTIVIRAL THERAPY; HOST PATHOGEN INTERACTION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFLUENZA; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; REVIEW; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; VIROGENESIS; VIRUS CELL INTERACTION; VIRUS MUTATION; VIRUS RESISTANCE; BIOLOGY; DRUG EFFECTS; FACTUAL DATABASE; HIV INFECTIONS; INFLUENZA, HUMAN; VIRUS REPLICATION;

HUMAN IMMUNODEFICIENCY VIRUS; ORTHOMYXOVIRIDAE;

ANTIVIRAL AGENTS; COMPUTATIONAL BIOLOGY; DATABASES, FACTUAL; HIV INFECTIONS; HOST-PATHOGEN INTERACTIONS; HUMANS; INFLUENZA, HUMAN; RNA INTERFERENCE; VIRUS REPLICATION;

EID: 79959760389     PISSN: None     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms12064027     Document Type: Review

References (134)

1. Coen, D.M.; Richman, D.D. Antiviral Agents. In Fields Virology, 5th ed.; Knipe, D.M., Howley, P.M., Eds.; Wolters Kluwer/Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2007; Volume 1, pp. 447-485.
2. Moore, C.; Galiano, M.; Lackenby, A.; Abdelrahman, T.; Barnes, R.; Evans, M.R.; Fegan, C.; Froude, S.; Hastings, M.; Knapper, S.; et al. Evidence of person-to-person transmission of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus in a hematology unit. J. Infect. Dis. 2011, 203, 18-24.
3. Sheu, T.G.; Fry, A.M.; Garten, R.J.; Deyde, V.M.; Shwe, T.; Bullion, L.; Peebles, P.J.; Li, Y.; Klimov, A.I.; Gubareva, L.V. Dual resistance to adamantanes and oseltamivir among seasonal influenza A(H1N1) viruses: 2008-2010. J. Infect. Dis. 2011, 203, 13-17.
4. Hayden, F.G.; de Jong, M.D. Emerging influenza antiviral resistance threats. J. Infect. Dis. 2011, 203, 6-10.
5. Walsh, C. Molecular mechanisms that confer antibacterial drug resistance. Nature 2000, 406, 775-781.
6. Cegelski, L.; Marshall, G.R.; Eldridge, G.R.; Hultgren, S.J. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 2008, 6, 17-27.
7. Schinazi, R.F.; Peters, J.; Williams, C.C.; Chance, D.; Nahmias, A.J. Effect of combinations of acyclovir with vidarabine or its 5'-monophosphate on herpes simplex viruses in cell culture and in mice. Antimicrob. Agents Chemother. 1982, 22, 499-507.
8. Kellam, P. Attacking pathogens through their hosts. Genome Biol. 2006, 7, 201.
9. Schwegmann, A.; Brombacher, F. Host-directed drug targeting of factors hijacked by pathogens. Sci. Signal. 2008, 1, re8.
10. Tan, S.L.; Ganji, G.; Paeper, B.; Proll, S.; Katze, M.G. Systems biology and the host response to viral infection. Nat. Biotechnol. 2007, 25, 1383-1389.
11. Koon, H.B.; Bubley, G.J.; Pantanowitz, L.; Masiello, D.; Smith, B.; Crosby, K.; Proper, J.; Weeden, W.; Miller, T.E.; Chatis, P.; et al. Imatinib-induced regression of AIDS-related Kaposi's sarcoma. J. Clin. Oncol. 2005, 23, 982-989.
12. Salerno, D.; Hasham, M.G.; Marshall, R.; Garriga, J.; Tsygankov, A.Y.; Grana, X. Direct inhibition of CDK9 blocks HIV-1 replication without preventing T-cell activation in primary human peripheral blood lymphocytes. Gene 2007, 405, 65-78.
13. Reeves, P.M.; Bommarius, B.; Lebeis, S.; McNulty, S.; Christensen, J.; Swimm, A.; Chahroudi, A.; Chavan, R.; Feinberg, M.B.; Veach, D.; et al. Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases. Nat. Med. 2005, 11, 731-739.
14. Hirsch, A.J.; Medigeshi, G.R.; Meyers, H.L.; DeFilippis, V.; Fruh, K.; Briese, T.; Lipkin, W.I.; Nelson, J.A. The Src family kinase c-Yes is required for maturation of West Nile virus particles. J. Virol. 2005, 79, 11943-11951.
15. Pearson, G.; Robinson, F.; Beers Gibson, T.; Xu, B.E.; Karandikar, M.; Berman, K.; Cobb, M.H. Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions. Endocr. Rev. 2001, 22, 153-183.
16. Pleschka, S.; Wolff, T.; Ehrhardt, C.; Hobom, G.; Planz, O.; Rapp, U.R.; Ludwig, S. Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade. Nat. Cell Biol. 2001, 3, 301-305.
17. Zhu, H.; Cong, J.P.; Yu, D.; Bresnahan, W.A.; Shenk, T.E. Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication. Proc. Natl. Acad. Sci. USA 2002, 99, 3932-3937.
18. Goldman, J.M.; Druker, B.J. Chronic myeloid leukemia: current treatment options. Blood 2001, 98, 2039-2042.
19. Ludwig, S. Targeting cell signalling pathways to fight the flu: Towards a paradigm change in anti-influenza therapy. J. Antimicrob. Chemother. 2009, 64, 1-4.
20. Newsome, T.P.; Scaplehorn, N.; Way, M. SRC mediates a switch from microtubule- to actin-based motility of vaccinia virus. Science 2004, 306, 124-129.
21. Kujime, K.; Hashimoto, S.; Gon, Y.; Shimizu, K.; Horie, T. p38 mitogen-activated protein kinase and c-jun-NH2-terminal kinase regulate RANTES production by influenza virus-infected human bronchial epithelial cells. J. Immunol. 2000, 164, 3222-3228.
22. Yoon, J.J.; Chawla, D.; Paal, T.; Ndungu, M.; Du, Y.; Kurtkaya, S.; Sun, A.; Snyder, J.P.; Plemper, R.K. High-throughput screening-based identification of paramyxovirus inhibitors. J. Biomol. Screen. 2008, 13, 591-608.
23. Bushell, K.M.; Sollner, C.; Schuster-Boeckler, B.; Bateman, A.; Wright, G.J. Large-scale screening for novel low-affinity extracellular protein interactions. Genome Res. 2008, 18, 622-630.
24. Fields, S.; Sternglanz, R. The two-hybrid system: an assay for protein-protein interactions. Trends Genet. 1994, 10, 286-292.
25. Chien, C.T.; Bartel, P.L.; Sternglanz, R.; Fields, S. The two-hybrid system: A method to identify and clone genes for proteins that interact with a protein of interest. Proc. Natl. Acad. Sci. USA 1991, 88, 9578-9582.
26. Kaur, G.; Roy, I. Therapeutic applications of aptamers. Expert Opin. Invest. Drugs 2008, 17, 43-60.
27. Borghouts, C.; Kunz, C.; Groner, B. Peptide aptamer libraries. Comb. Chem. High Throughput Screen. 2008, 11, 135-145.
28. Grimm, D.; Kay, M.A. Therapeutic application of RNAi: Is mRNA targeting finally ready for prime time? J. Clin. Invest. 2007, 117, 3633-3641.
29. Fewell, G.D.; Schmitt, K. Vector-based RNAi approaches for stable, inducible and genome-wide screens. Drug Discov. Today 2006, 11, 975-982.
30. Filipowicz, W.; Bhattacharyya, S.N.; Sonenberg, N. Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat. Rev. Genet. 2008, 9, 102-114.
31. Stenvang, J.; Kauppinen, S. MicroRNAs as targets for antisense-based therapeutics. Expert Opin. Biol. Ther. 2008, 8, 59-81.
32. Nguyen, D.G.; Yin, H.; Zhou, Y.; Wolff, K.C.; Kuhen, K.L.; Caldwell, J.S. Identification of novel therapeutic targets for HIV infection through functional genomic cDNA screening. Virology 2007, 362, 16-25.
33. Basha, S.; Rai, P.; Poon, V.; Saraph, A.; Gujraty, K.; Go, M.Y.; Sadacharan, S.; Frost, M.; Mogridge, J.; Kane, R.S. Polyvalent inhibitors of anthrax toxin that target host receptors. Proc. Natl. Acad. Sci. USA 2006, 103, 13509-13513.
34. Konig, R.; Stertz, S.; Zhou, Y.; Inoue, A.; Hoffmann, H.H.; Bhattacharyya, S.; Alamares, J.G.; Tscherne, D.M.; Ortigoza, M.B.; Liang, Y.; et al. Human host factors required for influenza virus replication. Nature 2010, 463, 813-817.
35. Karlas, A.; Machuy, N.; Shin, Y.; Pleissner, K.P.; Artarini, A.; Heuer, D.; Becker, D.; Khalil, H.; Ogilvie, L.A.; Hess, S.; et al. Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 2010, 463, 818-822.
36. Brass, A.L.; Dykxhoorn, D.M.; Benita, Y.; Yan, N.; Engelman, A.; Xavier, R.J.; Lieberman, J.; Elledge, S.J. Identification of host proteins required for HIV infection through a functional genomic screen. Science 2008, 319, 921-926.
37. Zhou, H.; Xu, M.; Huang, Q.; Gates, A.T.; Zhang, X.D.; Castle, J.C.; Stec, E.; Ferrer, M.; Strulovici, B.; Hazuda, D.J.; Espeseth, A.S. Genome-scale RNAi screen for host factors required for HIV replication. Cell Host Microbe 2008, 4, 495-504.
38. Borner, K.; Hermle, J.; Sommer, C.; Brown, N.P.; Knapp, B.; Glass, B.; Kunkel, J.; Torralba, G.; Reymann, J.; Beil, N.; et al. From experimental setup to bioinformatics: An RNAi screening platform to identify host factors involved in HIV-1 replication. Biotechnol. J. 2010, 5, 39-49.
39. Pache, L.; Konig, R.; Chanda, S.K. Identifying HIV-1 host cell factors by genome-scale RNAi screening. Methods 2011, 53, 3-12.
40. Krishnan, M.N.; Ng, A.; Sukumaran, B.; Gilfoy, F.D.; Uchil, P.D.; Sultana, H.; Brass, A.L.; Adametz, R.; Tsui, M.; Qian, F.; et al. RNA interference screen for human genes associated with West Nile virus infection. Nature 2008, 455, 242-245.
41. Li, Q.; Brass, A.L.; Ng, A.; Hu, Z.; Xavier, R.J.; Liang, T.J.; Elledge, S.J. A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proc. Natl. Acad. Sci. USA 2009, 106, 16410-16415.
42. Sigoillot, F.D.; King, R.W. Vigilance and Validation: Keys to Success in RNAi Screening. ACS Chem. Biol. 2011, 6, 47-60.
43. Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009, 37, 1-13.
44. Bard, J.B.; Rhee, S.Y. Ontologies in biology: design, applications and future challenges. Nat. Rev. Genet. 2004, 5, 213-222.
45. Rhee, S.Y.; Wood, V.; Dolinski, K.; Draghici, S. Use and misuse of the gene ontology annotations. Nat. Rev. Genet. 2008, 9, 509-515.
46. Chuang, H.Y.; Hofree, M.; Ideker, T. A decade of systems biology. Annu. Rev. Cell Dev. Biol. 2010, 26, 721-744.
47. Jensen, L.J.; Bork, P. Ontologies in quantitative biology: a basis for comparison, integration, and discovery. PLoS Biol. 2010, 8, e1000374.
48. Khatri, P.; Draghici, S. Ontological analysis of gene expression data: Current tools, limitations, and open problems. Bioinformatics 2005, 21, 3587-3595.
49. Ooi, H.S.; Schneider, G.; Chan, Y.L.; Lim, T.T.; Eisenhaber, B.; Eisenhaber, F. Databases of protein-protein interactions and complexes. Methods Mol. Biol. 2010, 609, 145-159.
50. Ooi, H.S.; Schneider, G.; Lim, T.T.; Chan, Y.L.; Eisenhaber, B.; Eisenhaber, F. Biomolecular pathway databases. Methods Mol. Biol. 2010, 609, 129-144.
51. Quackenbush, J. Computational analysis of microarray data. Nat. Rev. Genet. 2001, 2, 418-427.
52. Kanehisa, M.; Goto, S.; Furumichi, M.; Tanabe, M.; Hirakawa, M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 2010, 38, D355-D360.
53. Kanehisa, M.; Goto, S.; Hattori, M.; Aoki-Kinoshita, K.F.; Itoh, M.; Kawashima, S.; Katayama, T.; Araki, M.; Hirakawa, M. From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res. 2006, 34, D354-D357.
54. Kanehisa, M.; Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000, 28, 27-30.
55. Matthews, L.; Gopinath, G.; Gillespie, M.; Caudy, M.; Croft, D.; de Bono, B.; Garapati, P.; Hemish, J.; Hermjakob, H.; Jassal, B.; et al. Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res. 2009, 37, D619-D622.
56. Vastrik, I.; D'Eustachio, P.; Schmidt, E.; Gopinath, G.; Croft, D.; de Bono, B.; Gillespie, M.; Jassal, B.; Lewis, S.; Matthews, L.; et al. Reactome: A knowledge base of biologic pathways and processes. Genome Biol. 2007, 8, R39.
57. Joshi-Tope, G.; Vastrik, I.; Gopinath, G.R.; Matthews, L.; Schmidt, E.; Gillespie, M.; D'Eustachio, P.; Jassal, B.; Lewis, S.; Wu, G.; et al. The Genome Knowledgebase: A resource for biologists and bioinformaticists. Cold Spring Harb. Symp. Quant. Biol. 2003, 68, 237-243.
58. Thomas, P.D.; Campbell, M.J.; Kejariwal, A.; Mi, H.; Karlak, B.; Daverman, R.; Diemer, K.; Muruganujan, A.; Narechania, A. PANTHER: A library of protein families and subfamilies indexed by function. Genome Res. 2003, 13, 2129-2141.
59. Thomas, P.D.; Kejariwal, A.; Campbell, M.J.; Mi, H.; Diemer, K.; Guo, N.; Ladunga, I.; Ulitsky-Lazareva, B.; Muruganujan, A.; Rabkin, S.; et al. PANTHER: A browsable database of gene products organized by biological function, using curated protein family and subfamily classification. Nucleic Acids Res. 2003, 31, 334-341.
60. Pico, A.R.; Kelder, T.; van Iersel, M.P.; Hanspers, K.; Conklin, B.R.; Evelo, C. WikiPathways: Pathway editing for the people. PLoS Biol. 2008, 6, e184.
61. Karp, P.D.; Ouzounis, C.A.; Moore-Kochlacs, C.; Goldovsky, L.; Kaipa, P.; Ahren, D.; Tsoka, S.; Darzentas, N.; Kunin, V.; Lopez-Bigas, N., Expansion of the BioCyc collection of pathway/genome databases to 160 genomes. Nucleic Acids Res. 2005, 33, 6083-6089.
62. Lee, S.J.; Ways, J.A.; Barbato, J.C.; Essig, D.; Pettee, K.; DeRaedt, S.J.; Yang, S.; Weaver, D.A.; Koch, L.G.; Cicila, G.T. Gene expression profiling of the left ventricles in a rat model of intrinsic aerobic running capacity. Physiol. Genomics 2005, 23, 62-71.
63. Gene Ontology (GO). Available online: http://www.geneontology.org/ (accessed on 9 June 2011).
64. Szklarczyk, D.; Franceschini, A.; Kuhn, M.; Simonovic, M.; Roth, A.; Minguez, P.; Doerks, T.; Stark, M.; Muller, J.; Bork, P.; et al. The STRING database in 2011: Functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 2011, 39, D561-D568.
65. Jensen, L.J.; Kuhn, M.; Stark, M.; Chaffron, S.; Creevey, C.; Muller, J.; Doerks, T.; Julien, P.; Roth, A.; Simonovic, M.; et al. STRING 8-A global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res. 2009, 37, D412-D416.
66. von Mering, C.; Jensen, L.J.; Kuhn, M.; Chaffron, S.; Doerks, T.; Kruger, B.; Snel, B.; Bork, P. STRING 7-recent developments in the integration and prediction of protein interactions. Nucleic Acids Res. 2007, 35, D358-D362.
67. von Mering, C.; Jensen, L.J.; Snel, B.; Hooper, S.D.; Krupp, M.; Foglierini, M.; Jouffre, N.; Huynen, M.A.; Bork, P. STRING: Known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res. 2005, 33, D433-D437.
68. von Mering, C.; Huynen, M.; Jaeggi, D.; Schmidt, S.; Bork, P.; Snel, B. STRING: A database of predicted functional associations between proteins. Nucleic Acids Res. 2003, 31, 258-261.
69. Snel, B.; Lehmann, G.; Bork, P.; Huynen, M.A. STRING: A web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res. 2000, 28, 3442-3444.
70. Kuhn, M.; Szklarczyk, D.; Franceschini, A.; Campillos, M.; von Mering, C.; Jensen, L.J.; Beyer, A.; Bork, P. STITCH 2: An interaction network database for small molecules and proteins. Nucleic Acids Res. 2010, 38, D552-D556.
71. Kuhn, M.; von Mering, C.; Campillos, M.; Jensen, L.J.; Bork, P. STITCH: Interaction networks of chemicals and proteins. Nucleic Acids Res. 2008, 36, D684-688.
72. Dezso, Z.; Nikolsky, Y.; Nikolskaya, T.; Miller, J.; Cherba, D.; Webb, C.; Bugrim, A. Identifying disease-specific genes based on their topological significance in protein networks. BMC Syst. Biol. 2009, 3, DOI: 10.1186/1752-0509-3-36.
73. LaCount, D.J.; Vignali, M.; Chettier, R.; Phansalkar, A.; Bell, R.; Hesselberth, J.R.; Schoenfeld, L.W.; Ota, I.; Sahasrabudhe, S.; Kurschner, C.; et al. A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 2005, 438, 103-107.
74. Bader, G.D.; Hogue, C.W. BIND-a data specification for storing and describing biomolecular interactions, molecular complexes and pathways. Bioinformatics 2000, 16, 465-477.
75. Bader, G.D.; Donaldson, I.; Wolting, C.; Ouellette, B.F.; Pawson, T.; Hogue, C.W. BIND-The Biomolecular Interaction Network Database. Nucleic Acids Res. 2001, 29, 242-245.
76. Ceol, A.; Chatr Aryamontri, A.; Licata, L.; Peluso, D.; Briganti, L.; Perfetto, L.; Castagnoli, L.; Cesareni, G. MINT, the molecular interaction database: 2009 update. Nucleic Acids Res. 2010, 38, D532-D539.
77. Prasad, T.S.; Kandasamy, K.; Pandey, A. Human protein reference database and human proteinpedia as discovery tools for systems biology. Methods Mol. Biol. 2009, 577, 67-79.
78. Mishra, G.R.; Suresh, M.; Kumaran, K.; Kannabiran, N.; Suresh, S.; Bala, P.; Shivakumar, K.; Anuradha, N.; Reddy, R.; Raghavan, T.M.; et al. Human protein reference database-2006 update. Nucleic Acids Res 2006, 34, D411-D414.
79. Peri, S.; Navarro, J.D.; Amanchy, R.; Kristiansen, T.Z.; Jonnalagadda, C.K.; Surendranath, V.; Niranjan, V.; Muthusamy, B.; Gandhi, T.K.; Gronborg, M.; et al. Development of human protein reference database as an initial platform for approaching systems biology in humans. Genome Res. 2003, 13, 2363-2371.
80. Diez, D.; Wheelock, A.M.; Goto, S.; Haeggstrom, J.Z.; Paulsson-Berne, G.; Hansson, G.K.; Hedin, U.; Gabrielsen, A.; Wheelock, C.E. The use of network analyses for elucidating mechanisms in cardiovascular disease. Mol. Biosyst. 2010, 6, 289-304.
81. Tarca, A.L.; Draghici, S.; Khatri, P.; Hassan, S.S.; Mittal, P.; Kim, J.S.; Kim, C.J.; Kusanovic, J.P.; Romero, R. A novel signaling pathway impact analysis. Bioinformatics 2009, 25, 75-82.
82. Qu, X.A.; Gudivada, R.C.; Jegga, A.G.; Neumann, E.K.; Aronow, B.J. Inferring novel disease indications for known drugs by semantically linking drug action and disease mechanism relationships. BMC Bioinformatics 2009, 10, DOI: 10.1186/1471-2105-10-S5-S4.
83. Sthoeger, Z.M.; Zinger, H.; Mozes, E. Beneficial effects of the anti-oestrogen tamoxifen on systemic lupus erythematosus of (NZBxNZW)F1 female mice are associated with specific reduction of IgG3 autoantibodies. Ann. Rheum. Dis. 2003, 62, 341-346.
84. Cohen-Solal, J.F.; Jeganathan, V.; Grimaldi, C.M.; Peeva, E.; Diamond, B. Sex hormones and SLE: influencing the fate of autoreactive B cells. Curr. Top. Microbiol. Immunol. 2006, 305, 67-88.
85. Wishart, D.S.; Knox, C.; Guo, A.C.; Cheng, D.; Shrivastava, S.; Tzur, D.; Gautam, B.; Hassanali, M. DrugBank: A knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008, 36, D901-D906.
86. Wishart, D.S.; Knox, C.; Guo, A.C.; Shrivastava, S.; Hassanali, M.; Stothard, P.; Chang, Z.; Woolsey, J. DrugBank: A comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006, 34, D668-D672.
87. Kellenberger, E.; Muller, P.; Schalon, C.; Bret, G.; Foata, N.; Rognan, D. sc-PDB: An annotated database of druggable binding sites from the Protein Data Bank. J. Chem. Inf. Model. 2006, 46, 717-727.
88. Berman, H.M.; Bhat, T.N.; Bourne, P.E.; Feng, Z.; Gilliland, G.; Weissig, H.; Westbrook, J. The Protein Data Bank and the challenge of structural genomics. Nat. Struct. Biol. 2000, 7, 957-959.
89. Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235-242.
90. Li, Q.; Cheng, T.; Wang, Y.; Bryant, S.H. PubChem as a public resource for drug discovery. Drug Discov. Today 2010, 15, 1052-1057.
91. Olah, M.; Rad, R.; Ostopovici, L.; Bora, A.; Hadaruga, N.; Hadaruga, R.; Moldovan, R.; Fulias, A.; Mracec, M.; Opera, T.I. WOMBAT and WOMBAT-PK: Bioactivity Databases for Lead and Drug Discovery. In Chemical Biology: From Small Molecules to Systems Biology and Drug Design; Schreiber, S.L., Kapoor, T.M., Wess, G., Eds.; Wiley-VCH: New York, NY, USA, 2007; pp. 760-786.
92. Opera, T.I.; Benedetti, P.; Berellini, G.; Olah, M.; Fejgin, K.; Boyer, S. Rapid ADME Filters for Lead Discovery In Molecular Interactions Field; Cruciani, G., Ed.; Wiley-VCH: New York, NY, USA, 2006; pp. 249-272.
93. Scheer, M.; Grote, A.; Chang, A.; Schomburg, I.; Munaretto, C.; Rother, M.; Sohngen, C.; Stelzer, M.; Thiele, J.; Schomburg, D. BRENDA, the enzyme information system in 2011. Nucleic Acids Res. 2011, 39, D670-D676.
94. Shoichet, B.K. Virtual screening of chemical libraries. Nature 2004, 432, 862-865.
95. Konig, R.; Zhou, Y.Y.; Elleder, D.; Diamond, T.L.; Bonamy, G.M.C.; Irelan, J.T.; Chiang, C.Y.; Tu, B.P.; De Jesus, P.D.; Lilley, C.E.; et al. Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 2008, 135, 49-60.
96. Bushman, F.D.; Malani, N.; Fernandes, J.; D'Orso, I.; Cagney, G.; Diamond, T.L.; Zhou, H.L.; Hazuda, D.J.; Espeseth, A.S.; Konig, R.; et al. Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies. PLoS Pathog. 2009, 5, e1000437.
97. Barrows, N.J.; Le Sommer, C.; Garcia-Blanco, M.A.; Pearson, J.L. Factors affecting reproducibility between genome-scale siRNA-based screens. J. Biomol. Screen. 2010, 15, 735-747.
98. Gene Ontology Consortium. The Gene Ontology in 2010: Extensions and refinements. Nucleic Acids Res. 2010, 38, D331-D335.
99. The Reference Genome Group of the Gene Ontology Consortium. The Gene Ontology's Reference Genome Project: A unified framework for functional annotation across species. PLoS Comput. Biol. 2009, 5, e1000431.
100. Dennis, G., Jr.; Sherman, B.T.; Hosack, D.A.; Yang, J.; Gao, W.; Lane, H.C.; Lempicki, R.A. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003, 4, R60:1-R60:11.
101. Fu, W.; Sanders-Beer, B.E.; Katz, K.S.; Maglott, D.R.; Pruitt, K.D.; Ptak, R.G. Human immunodeficiency virus type 1, human protein interaction database at NCBI. Nucleic Acids Res. 2009, 37, D417-D422.
102. Garrus, J.E.; von Schwedler, U.K.; Pornillos, O.W.; Morham, S.G.; Zavitz, K.H.; Wang, H.E.; Wettstein, D.A.; Stray, K.M.; Cote, M.; Rich, R.L.; et al. Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 2001, 107, 55-65.
103. Kilzer, J.M.; Stracker, T.; Beitzel, B.; Meek, K.; Weitzman, M.; Bushman, F.D. Roles of host cell factors in circularization of retroviral dna. Virology 2003, 314, 460-467.
104. Wei, P.; Garber, M.E.; Fang, S.M.; Fischer, W.H.; Jones, K.A. A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell 1998, 92, 451-462.
105. Yedavalli, V.S.; Neuveut, C.; Chi, Y.H.; Kleiman, L.; Jeang, K.T. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell 2004, 119, 381-392.
106. Fellay, J.; Shianna, K.V.; Ge, D.; Colombo, S.; Ledergerber, B.; Weale, M.; Zhang, K.; Gumbs, C.; Castagna, A.; Cossarizza, A.; et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007, 317, 944-947.
107. Matthews, P.C.; Prendergast, A.; Leslie, A.; Crawford, H.; Payne, R.; Rousseau, C.; Rolland, M.; Honeyborne, I.; Carlson, J.; Kadie, C.; et al. Central role of reverting mutations in HLA associations with human immunodeficiency virus set point. J. Virol. 2008, 82, 8548-8559.
108. Cherepanov, P. LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic Acids Res. 2007, 35, 113-124.
109. Cherepanov, P.; Maertens, G.; Proost, P.; Devreese, B.; Van Beeumen, J.; Engelborghs, Y.; De Clercq, E.; Debyser, Z. HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. J. Biol. Chem. 2003, 278, 372-381.
110. Ciuffi, A.; Bushman, F.D. Retroviral DNA integration: HIV and the role of LEDGF/p75. Trends Genet. 2006, 22, 388-395.
111. Gamble, T.R.; Vajdos, F.F.; Yoo, S.; Worthylake, D.K.; Houseweart, M.; Sundquist, W.I.; Hill, C.P. Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell 1996, 87, 1285-1294.
112. Llano, M.; Saenz, D.T.; Meehan, A.; Wongthida, P.; Peretz, M.; Walker, W.H.; Teo, W.; Poeschla, E.M. An essential role for LEDGF/p75 in HIV integration. Science 2006, 314, 461-464.
113. Maertens, G.; Cherepanov, P.; Pluymers, W.; Busschots, K.; De Clercq, E.; Debyser, Z.; Engelborghs, Y. LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J. Biol. Chem. 2003, 278, 33528-33539.
114. Marshall, H.M.; Ronen, K.; Berry, C.; Llano, M.; Sutherland, H.; Saenz, D.; Bickmore, W.; Poeschla, E.; Bushman, F.D. Role of PSIP1/LEDGF/p75 in lentiviral infectivity and integration targeting. PLoS One 2007, 2, e1340.
115. Turlure, F.; Devroe, E.; Silver, P.A.; Engelman, A. Human cell proteins and human immunodeficiency virus DNA integration. Front. Biosci. 2004, 9, 3187-3208.
116. Ciuffi, A.; Llano, M.; Poeschla, E.; Hoffmann, C.; Leipzig, J.; Shinn, P.; Ecker, J.R.; Bushman, F. A role for LEDGF/p75 in targeting HIV DNA integration. Nat. Med. 2005, 11, 1287-1289.
117. Llano, M.; Vanegas, M.; Fregoso, O.; Saenz, D.; Chung, S.; Peretz, M.; Poeschla, E.M. LEDGF/p75 determines cellular trafficking of diverse lentiviral but not murine oncoretroviral integrase proteins and is a component of functional lentiviral preintegration complexes. J. Virol. 2004, 78, 9524-9537.
118. Hao, L.; Sakurai, A.; Watanabe, T.; Sorensen, E.; Nidom, C.A.; Newton, M.A.; Ahlquist, P.; Kawaoka, Y. Drosophila RNAi screen identifies host genes important for influenza virus replication. Nature 2008, 454, 890-893.
119. Brass, A.L.; Huang, I.C.; Benita, Y.; John, S.P.; Krishnan, M.N.; Feeley, E.M.; Ryan, B.J.; Weyer, J.L.; van der Weyden, L.; Fikrig, E.; et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 2009, 139, 1243-1254.
120. Shapira, S.D.; Gat-Viks, I.; Shum, B.O.; Dricot, A.; de Grace, M.M.; Wu, L.; Gupta, P.B.; Hao, T.; Silver, S.J.; Root, D.E.; et al. A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell 2009, 139, 1255-1267.
121. Josset, L.; Textoris, J.; Loriod, B.; Ferraris, O.; Moules, V.; Lina, B.; N'Guyen, C.; Diaz, J.J.; Rosa-Calatrava, M. Gene expression signature-based screening identifies new broadly effective influenza a antivirals. PLoS One 2010, 5, e13169.
122. Coombs, K.M.; Berard, A.; Xu, W.; Krokhin, O.; Meng, X.; Cortens, J.P.; Kobasa, D.; Wilkins, J.; Brown, E.G. Quantitative proteomic analyses of influenza virus-infected cultured human lung cells. J. Virol. 2010, 84, 10888-10906.
123. Watanabe, T.; Watanabe, S.; Kawaoka, Y. Cellular networks involved in the influenza virus life cycle. Cell Host Microbe 2010, 7, 427-439.
124. Min, J.Y.; Subbarao, K. Cellular targets for influenza drugs. Nat. Biotechnol. 2010, 28, 239-240.
125. Chase, G.; Deng, T.; Fodor, E.; Leung, B.W.; Mayer, D.; Schwemmle, M.; Brownlee, G. Hsp90 inhibitors reduce influenza virus replication in cell culture. Virology 2008, 377, 431-439.
126. Gonzalez, O.; Fontanes, V.; Raychaudhuri, S.; Loo, R.; Loo, J.; Arumugaswami, V.; Sun, R.; Dasgupta, A.; French, S.W. The heat shock protein inhibitor Quercetin attenuates hepatitis C virus production. Hepatology 2009, 50, 1756-1764.
127. Soh, D.; Dong, D.; Guo, Y.; Wong, L. Consistency, comprehensiveness, and compatibility of pathway databases. BMC Bioinformatics 2010, 11, 449.F
128. Ingenuity Systems. Available online: http://www.ingenuity.com/index.html (accessed on 6 January 2011).
129. Konig, R.; Stertz, S.; Zhou, Y.; Inoue, A.; Hoffmann, H.H.; Bhattacharyya, S.; Alamares, J. G.; Tscherne, D. M.; Ortigoza, M. B.; Liang, Y.; Gao, Q.; Andrews, S.E.; Bandyopadhyay, S.; De Jesus, P.; Tu, B.P.; Pache, L.; Shih, C.; Orth, A.; Bonamy, G.; Miraglia, L.; Ideker, T.; Garcia-Sastre, A.; Young, J.A.; Palese, P.; Shaw, M.L.; Chanda, S.K. Human host factors required for influenza virus replication. Nature 2010, 463, 813-817.
130. Karlas, A.; Machuy, N.; Shin, Y.; Pleissner, K. P.; Artarini, A.; Heuer, D.; Becker, D.; Khalil, H.; Ogilvie, L.A.; Hess, S.; Maurer, A.P.; Muller, E.; Wolff, T.; Rudel, T.; Meyer, T.F. Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 2010, 463, 818-822.
131. Brass, A.L.; Huang, I.C.; Benita, Y.; John, S.P.; Krishnan, M.N.; Feeley, E.M.; Ryan, B.J.; Weyer, J.L.; van der Weyden, L.; Fikrig, E.; Adams, D.J.; Xavier, R.J.; Farzan, M.; Elledge, S.J. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 2009, 139, 1243-1254.
132. Shapira, S.D.; Gat-Viks, I.; Shum, B.O.; Dricot, A.; de Grace, M.M.; Wu, L.; Gupta, P.B.; Hao, T.; Silver, S. J.; Root, D. E.; Hill, D. E.; Regev, A.; Hacohen, N., A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell 2009, 139, 1255-1267.
133. Josset, L.; Textoris, J.; Loriod, B.; Ferraris, O.; Moules, V.; Lina, B.; N'Guyen, C.; Diaz, J.J.; Rosa-Calatrava, M., Gene expression signature-based screening identifies new broadly effective influenza a antivirals. PLoS One 2010, 5.
134. Chen, Y.L.; Chen, W.W.; Wang, Y.F.; Li, R.L.; Guo, W.F.; Lao, S.X.; Wang, J.H.; Huang, S.P. Bioinformatics research on chronic superficial gastritis of Pi-deficiency syndrome by gene arrays. Chin. J. Integr. Med. 2009, 15, 341-346.