Small molecules VP-14637 and JNJ-2408068 inhibit respiratory syncytial virus fusion by similar mechanisms

Antimicrobial Agents and Chemotherapy

Volumn 49, Issue 6, 2005, Pages 2460-2466

  Douglas, Janet L ^a   Panis, Marites L ^a   Ho, Edmund ^a   Lin, Kuei Ying ^a   Krawczyk, Steve H ^a   Grant, Deborah M ^a   Cai, Ruby ^a   Swaminathan, Swami ^a   Chen, Xiaowu ^a   Cihlar, Tomas ^a  

^a Gilead   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [[2 [[1 (2 AMINOETHYL) 4 PIPERIDINYL]AMINO] 4 METHYL 1H BENZIMIDAZOL 1 YL] 6 METHYL 3 PYRIDINOL]; 5,5' BIS[1 [(5 AMINO 1H TETRAZOLYL)IMINO]METHYL] 2,2'4'' METHYLIDYNETRISPHENOL; ANTIVIRUS AGENT; BENZIMIDAZOLE DERIVATIVE; BENZOTRIAZOLE DERIVATIVE; JNJ 2408068; R 170591; UNCLASSIFIED DRUG; VIRUS F PROTEIN; VIRUS PROTEIN; VP 14637;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ANTIBIOTIC RESISTANCE; ARTICLE; CELL STRAIN BHK; CELL STRAIN HEPG2; CONCENTRATION RESPONSE; CONTROLLED STUDY; CROSS RESISTANCE; DRUG BINDING; DRUG EFFECT; DRUG MECHANISM; DRUG STRUCTURE; GENE EXPRESSION SYSTEM; GENE MUTATION; HUMAN; HUMAN CELL; HYDROPHOBICITY; IC 50; MOLECULAR MODEL; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; RESPIRATORY SYNCYTIAL PNEUMOVIRUS; VACCINIA VIRUS; VIRUS INHIBITION;

ANIMALS; ANTIVIRAL AGENTS; BENZIMIDAZOLES; CELL FUSION; CELL LINE; CHICK EMBRYO; CRICETINAE; DRUG RESISTANCE, VIRAL; HUMANS; MEMBRANE FUSION; MODELS, MOLECULAR; PHENOLS; RESPIRATORY SYNCYTIAL VIRUS, HUMAN; TETRAZOLES; VIRAL FUSION PROTEINS;

EID: 21144442487     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.49.6.2460-2466.2005     Document Type: Article

References (25)

1. Andries, K., M. Moeremans, T. Gevers, R. Willebrords, C. Sommen, J. Lacrampe, F. Janssens, and P. R. Wyde. 2003. Substituted benzimidazoles with nanomolar activity against respiratory syncytial virus. Antiviral Res. 60:209-219.
2. Chan, D. C., C. T. Chutkowski, and P. S. Kim. 1998. Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target. Proc. Natl. Acad. Sci. USA 95:15613-15617.
3. Chen, L., J. J. German, J. McKimm-Breschkin, L. J. Lawrence, P. A. Tulloch, B. J. Smith, P. M. Colman, and M. C. Lawrence. 2001. The structure of the fusion glycoprotein of Newcastle disease virus suggests a novel paradigm for the molecular mechanism of membrane fusion. Structure 9:255-266.
4. Cianci, C., K. L. Yu, K. Combrink, N. Sin, B. Pearce, A. Wang, R. Civiello, S. Voss, G. Luo, K. Kadow, E. V. Genovesi, B. Venables, H. Gulgeze, A. Trehan, J. James, L. Lamb, I. Medina, J. Roach, Z. Yang, L. Zadjura, R. Colonno, J. Clark, N. Meanwell, and M. Krystal. 2004. Orally active fusion inhibitor of respiratory syncytial virus. Antimicrob. Agents Chemother. 48: 413-422.
5. Cianci, C., D. R. Langley, D. D. Dischino, Y. Sun, K. L. Yu, A. Stanley, J. Roach, Z. Li, R. Dalterio, R. Colonno, N. A. Meanwell, and M. Krystal. 2004. Targeting a binding pocket within the trimer-of-hairpins: small-molecule inhibition of viral fusion. Proc. Natl. Acad. Sci. USA 101:15046-15051.
6. Collins, P. L., R. M. Chanock, and B. R. Murphy. 2001. Respiratory syncytial virus, p. 1443-1485. In D. M. Knipe and P. M. Howley (ed.), Fields virology, 4th ed., vol. 1. Lippincott Williams & Wilkins, Philadelphia, Pa.
7. Douglas, J. L., M. L. Panis, E. Ho, K. Y. Lin, S. H. Krawczyk, D. M. Grant, R. Cai, S. Swaminathan, and T. Cihlar. 2003. Inhibition of respiratory syncytial virus fusion by the small molecule VP-14637 via specific interactions with F protein. J. Virol. 77:5054-5064.
8. Falsey, A. R. 1998. Respiratory syncytial virus infection in older persons. Vaccine 16:1775-1778.
9. Groothuis, J. R., E. A. Simoes, M. J. Levin, C. B. Hall, C. E. Long, W. J. Rodriguez, J. Arrobio, H. C. Meissner, D. R. Fulton, R. C. Welliver, D. A. Tristram, G. R. Siber, G. A. Prince, M. Van Raden, and V. G. Hemming. 1993. Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. N. Engl. J. Med. 329:1524-1530.
10. Johnson, S., C. Oliver, G. A. Prince, V. G. Hemming, D. S. Pfarr, S. C. Wang, M. Dormitzer, J. O'Grady, G. Koenig, J. K. Tamura, R. Woods, G. Bansal, D. Couchenour, E. Tsao, C. Hall, and J. F. Young. 1997. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J. Infect. Dis. 176:1215-1224.
11. Lambert, D. M., S. Barney, A. L. Lambert, K. Guthrie, R. Medinas, D. E. Davis, T. Bucy, J. Erickson, G. Merutka, and S. R. Petteway, Jr. 1996. Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. Proc. Natl. Acad. Sci. USA 93:2186-2191.
12. Lawless-Delmedico, M. K., P. Sista, R. Sen, N. C. Moore, J. B. Antczak, J. M. White, R. J. Greene, K. C. Leanza, T. J. Matthews, and D. M. Lambert. 2000. Heptad-repeat regions of respiratory syncytial virus F1 protein form a six-membered coiled-coil complex. Biochemistry 39:11684-11695.
13. Matthews, J. M., T. F. Young, S. P. Tucker, and J. P. Mackay. 2000. The core of the respiratory syncytial virus fusion protein is a trimeric coiled coil. J. Virol. 74:5911-5920.
14. McKimm-Breschkin, J. 2000. VP-14637 ViroPharma. Curr. Opin. Investig. Drugs 1:425-427.
15. Morton, C. J., R. Cameron, L. J. Lawrence, B. Lin, M. Lowe, A. Luttick, A. Mason, J. McKimm-Breschkin, M. W. Parker, J. Ryan, M. Smout, J. Sullivan, S. P. Tucker, and P. R. Young. 2003. Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay. Virology 311:275-288.
16. Razinkov, V., A. Gazumyan, A. Nikitenko, G. Ellestad, and G. Krishnamurthy. 2001. RFI-641 inhibits entry of respiratory syncytial virus via interactions with fusion protein. Chem. Biol. 8:645-659.
17. Simoes, E. A. 2003. Environmental and demographic risk factors for respiratory syncytial virus lower respiratory tract disease. J. Pediatr. 143:S118-S126.
18. Smith, B. J., M. C. Lawrence, and P. M. Colman. 2002. Modelling the structure of the fusion protein from human respiratory syncytial virus. Protein Eng. 15:365-371.
19. Vujovic, O., and J. Mills. 2001. Preventive and therapeutic strategies for respiratory syncytial virus infection. Curr. Opin. Pharmacol. 1:497-503.
20. Welliver, R. C. 2003. Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection. J. Pediatr. 143:5112-8117.
21. Wyatt, L. S., B. Moss, and S. Rozenblatt. 1995. Replication-deficient vaccinia virus encoding bacteriophage T7 RNA polymerase for transient gene expression in mammalian cells. Virology 210:202-205.
22. Wyde, P. R., S. N. Chetty, P. Timmerman, B. E. Gilbert, and K. Andries. 2003. Short duration aerosols of JNJ 2408068 (R170591) administered prophylactically or therapeutically protect cotton rats from experimental respiratory syncytial virus infection. Antiviral Res. 60:221-231.
23. Wyde, P. R., D. K. Moore-Poveda, B. O'Hara, W. D. Ding, B. Mitsner, and B. E. Gilbert. 1998. CL387626 exhibits marked and unusual antiviral activity against respiratory virus in tissue culture and in cotton rats. Antiviral Res. 38:31-42.
24. Yu, K. L., Y. Zhang, R. L. Civiello, K. F. Kadow, C. Cianci, M. Krystal, and N. A. Meanwell. 2003. Fundamental structure-activity relationships associated with a new structural class of respiratory syncytial virus inhibitor. Bioorg. Med. Chem. Lett. 13:2141-2144.
25. Zhao, X., M. Singh, V. N. Malashkevich, and P. S. Kim. 2000. Structural characterization of the human respiratory syncytial virus fusion protein core. Proc. Natl. Acad. Sci. USA 97:14172-14177.