Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 19, 2016, Pages 5388-5393

  Brai, Annalaura ^a   Fazi, Roberta ^a   Tintori, Cristina ^a   Zamperini, Claudio ^a   Bugli, Francesca ^b   Sanguinetti, Maurizio ^b   Stigliano, Egidio ^c   Esté, José ^d   Badia, Roger ^d   Franco, Sandra ^d   Martinez, Miguel A ^d   Martinez, Javier P ^e   Meyerhans, Andreas ^e,f   Saladini, Francesco ^a   Zazzi, Maurizio ^a   Garbelli, Anna ^g   Maga, Giovanni ^g   Botta, Maurizio ^a,h,i  

^a UNIVERSITY OF SIENA   (Italy)

^b CATHOLIC UNIVERSITY   (Italy)

^c FONDAZIONE POLICLINICO UNIVERSITARIO A GEMELLI IRCCS   (Italy)

^d HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

^e UNIVERSITAT POMPEU FABRA   (Spain)

^f INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

^g CNR   (Italy)

^h Temple University   (United States)

ⁱ Lead Discovery Siena Srl   (Italy)

Author keywords

Broad spectrum antivirals; Coinfections; DDX3; Host factors; Resistance

Indexed keywords

ADENOSINE TRIPHOSPHATASE; ANTIVIRUS AGENT; DEAD BOX POLYPEPTIDE 1; DEAD BOX POLYPEPTIDE 3; DEAD BOX POLYPEPTIDE 3 INHIBITOR; DEAD BOX PROTEIN; ENZYME INHIBITOR; HELICASE; NONSTRUCTURAL PROTEIN 3; UNCLASSIFIED DRUG; DDX3X PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BINDING SITE; COMPETITIVE INHIBITION; CONTROLLED STUDY; DENGUE VIRUS; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG HALF LIFE; DRUG PROTEIN BINDING; DRUG TARGETING; DRUG TISSUE LEVEL; DRUG TOLERANCE; ENZYMATIC ASSAY; ENZYME INHIBITION; HEPATITIS C VIRUS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IC50; IN VITRO STUDY; NONHUMAN; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; RAT; RNA BINDING; STRUCTURE ACTIVITY RELATION; WEST NILE VIRUS; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; METABOLISM; MOLECULARLY TARGETED THERAPY; PHYSIOLOGY; PROCEDURES; VIRUS REPLICATION;

ANTIVIRAL AGENTS; DEAD-BOX RNA HELICASES; DRUG DESIGN; ENZYME INHIBITORS; MOLECULAR TARGETED THERAPY; VIRUS REPLICATION;

EID: 84966277154     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1522987113     Document Type: Article

References (44)

1. Lou Z, Sun Y, Rao Z (2014) Current progress in antiviral strategies. Trends Pharmacol Sci 35(2):86-102.
2. Bekerman E, Einav S (2015) Infectious disease. Combating emerging viral threats. Science 348(6232):282-283.
3. Dorr P, et al. (2005) Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother 49(11):4721-4732.
4. Gallay PA, Lin K (2013) Profile of alisporivir and its potential in the treatment of hepatitis C. Drug Des Devel Ther 7:105-115.
5. Ahlquist P, Noueiry AO, Lee WM, Kushner DB, Dye BT (2003) Host factors in positivestrand RNA virus genome replication. J Virol 77(15):8181-8186.
6. Prussia A, Thepchatri P, Snyder JP, Plemper RK (2011) Systematic approaches towards the development of host-directed antiviral therapeutics. Int J Mol Sci 12(6): 4027-4052.
7. Scheller N, et al. (2009) Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates. Proc Natl Acad Sci USA 106(32):13517-13522.
8. Drake JW, Holland JJ (1999) Mutation rates among RNA viruses. Proc Natl Acad Sci USA 96(24):13910-13913.
9. Gianella S, Richman DD (2010) Minority variants of drug-resistant HIV. J Infect Dis 202(5):657-666.
10. Duffy S, Shackelton LA, Holmes EC (2008) Rates of evolutionary change in viruses: Patterns and determinants. Nat Rev Genet 9(4):267-276.
11. Ruiz A, Russell SJ (2012) A new paradigm in viral resistance. Cell Res 22(11):1515-1517.
12. Martinez JP, Sasse F, Brönstrup M, Diez J, Meyerhans A (2015) Antiviral drug discovery: Broad-spectrum drugs from nature. Nat Prod Rep 32(1):29-48.
13. Lenarcic EM, Ziehr BJ, Moorman NJ (2015) An unbiased proteomics approach to identify human cytomegalovirus RNA-associated proteins. Virology 481:13-23.
14. Yedavalli VS, Neuveut C, Chi YH, Kleiman L, Jeang KT (2004) Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell 119(3):381-392.
15. Owsianka AM, Patel AH (1999) Hepatitis C virus core protein interacts with a human DEAD box protein DDX3. Virology 257(2):330-340.
16. Mamiya N, Worman HJ (1999) Hepatitis C virus core protein binds to a DEAD box RNA helicase. J Biol Chem 274(22):15751-15756.
17. You LR, et al. (1999) Hepatitis C virus core protein interacts with cellular putative RNA helicase. J Virol 73(4):2841-2853.
18. Ariumi Y, et al. (2007) DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication. J Virol 81(24):13922-13926.
19. Li C, et al. (2014) Cellular DDX3 regulates Japanese encephalitis virus replication by interacting with viral un-translated regions. Virology 449:70-81.
20. Noble CG, et al. (2010) Strategies for development of Dengue virus inhibitors. Antiviral Res 85(3):450-462.
21. Chahar HS, Chen S, Manjunath N (2013) P-body components LSM1, GW182, DDX3, DDX6 and XRN1 are recruited to WNV replication sites and positively regulate viral replication. Virology 436(1):1-7.
22. Schröder M, Baran M, Bowie AG (2008) Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J 27(15):2147-2157.
23. Kalverda AP, et al. (2009) Poxvirus K7 protein adopts a Bcl-2 fold: Biochemical mapping of its interactions with human DEAD box RNA helicase DDX3. J Mol Biol 385(3): 843-853.
24. Benfield CT, Ren H, Lucas SJ, Bahsoun B, Smith GL (2013) Vaccinia virus protein K7 is a virulence factor that alters the acute immune response to infection. JGenVirol94(Pt 7): 1647-1657.
25. Vashist S, Urena L, Chaudhry Y, Goodfellow I (2012) Identification of RNA-protein interaction networks involved in the norovirus life cycle. J Virol 86(22):11977-11990.
26. Schröder M (2011) Viruses and the human DEAD-box helicase DDX3: Inhibition or exploitation? Biochem Soc Trans 39(2):679-683.
27. Tintori C, et al. (2014) Protein-protein interactions and human cellular cofactors as new targets for HIV therapy. Curr Opin Pharmacol 18:1-8.
28. Dürr R, et al. (2014) Targeting cellular cofactors in HIV therapy. Topics in Medicinal Chemistry, eds Diederich WE, Steuber H (Springer, Heidelberg), pp 183-222.
29. Yedavalli VS, et al. (2008) Ring expanded nucleoside analogues inhibit RNA helicase and intracellular human immunodeficiency virus type 1 replication. J Med Chem 51(16):5043-5051.
30. Zhang N, Zhang P, Baier A, Cova L, Hosmane RS (2014) Dual inhibition of HCV and HIV by ring-expanded nucleosides containing the 5:7-fused imidazo[4,5-e][1,3]diazepine ring system. In vitro results and implications. Bioorg Med Chem Lett 24(4):1154-1157.
31. Garbelli A, et al. (2011) Targeting the human DEAD-box polypeptide 3 (DDX3) RNA helicase as a novel strategy to inhibit viral replication. Curr Med Chem 18(20):3015-3027.
32. Maga G, et al. (2008) Pharmacophore modeling and molecular docking led to the discovery of inhibitors of human immunodeficiency virus-1 replication targeting the human cellular aspartic acid-glutamic acid-alanine-aspartic acid box polypeptide 3. J Med Chem 51(21):6635-6638.
33. Samal SK, Routray S, Veeramachaneni GK, Dash R, Botlagunta M (2015) Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer. Sci Rep 5:9982.
34. Bol GM, et al. (2015) Targeting DDX3 with a small molecule inhibitor for lung cancer therapy. EMBO Mol Med 7(5):648-669.
35. Bantscheff M, Scholten A, Heck AJ (2009) Revealing promiscuous drug-target interactions by chemical proteomics. Drug Discov Today 14(21-22):1021-1029.
36. Radi M, et al. (2012) Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: Towards the next generation HIV-1 inhibitors. Bioorg Med Chem Lett 22(5):2094-2098.
37. Fazi R, et al. (2015) Homology model-based virtual screening for the identification of human helicase DDX3 inhibitors. J Chem Inf Model 55(11):2443-2454.
38. Verdonk ML, Cole JC, Hartshorn MJ, Murray CW, Taylor RD (2003) Improved proteinligand docking using GOLD. Proteins 52(4):609-623.
39. Cole JC, Nissink JWM, Taylor R (2005) Protein-ligand docking and virtual screening with GOLD. Virtual Screening in Drug Discovery, eds Shoichet B, Alvarez J (Taylor & Francis CRC Press, Boca Raton, FL).
40. PyMOL (2011) PyMOL Molecular Graphics System, Version 0.99 (Schrödinger, LLC, New York, NY).
41. Pannecouque C, Daelemans D, De Clercq E (2008) Tetrazolium-based colorimetric assay for the detection of HIV replication inhibitors: Revisited 20 years later. Nat Protoc 3(3):427-434.
42. Wohnsland F, Faller B (2001) High-throughput permeability pH profile and highthroughput alkane/water log P with artificial membranes. J Med Chem 44(6): 923-930.
43. Sugano K, et al. (2001) High throughput prediction of oral absorption: Improvement of the composition of the lipid solution used in parallel artificial membrane permeation assay. J Biomol Screen 6(3):189-196.
44. Shumaker RC (1986) PKCALC: A BASIC interactive computer program for statistical and pharmacokinetic analysis of data. Drug Metab Rev 17(3-4):331-348.