Novel diversity-oriented synthesis-derived respiratory syncytial virus inhibitors identified via a high throughput replicon-based screen

Antiviral Research

Volumn 131, Issue , 2016, Pages 19-25

  Duvall, Jeremy R ^a   Verplank, Lynn ^a   Ludeke, Barbara ^b   McLeod, Sarah M ^c   Lee, Maurice D ^a   Vishwanathan, Karthick ^c   Mulrooney, Carol A ^a   Le Quement, Sebastian ^a   Yu, Qin ^c   Palmer, Michelle A ^a   Fleming, Paul ^c   Fearns, Rachel ^b   Foley, Michael A ^a   Scherer, Christina A ^a  

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^b BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c ASTRAZENECA   (United Kingdom)

Author keywords

Diversity oriented synthesis; Replicon; Respiratory syncytial virus

Indexed keywords

ANTIVIRUS AGENT; BRD 3482; BRD 3969; BRD 4517; BRD 5449; BRD 65768; BRD 6801; BRD 9101; BRD 9259; UNCLASSIFIED DRUG; RNA DIRECTED RNA POLYMERASE; VIRAL PROTEIN;

ARTICLE; DIVERSITY ORIENTED SYNTHESIS; HEPATIC CLEARANCE; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; HUMAN RESPIRATORY SYNCYTIAL VIRUS; NONHUMAN; PLASMA PROTEIN BINDING; PRIORITY JOURNAL; REPLICON; RESPIRATORY SYNCYTIAL VIRUS INFECTION; RNA SYNTHESIS; STRUCTURE ACTIVITY RELATION; VIRUS GENOME; VIRUS INHIBITION; VIRUS REPLICATION; VIRUS STRAIN; VIRUS TRANSCRIPTION; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; ENZYMOLOGY; HEP-G2 CELL LINE; ISOLATION AND PURIFICATION; MICROBIAL SENSITIVITY TEST; PHYSIOLOGY; PROCEDURES; RESPIRATORY SYNCYTIAL VIRUS INFECTIONS; VIROLOGY;

ANTIVIRAL AGENTS; DRUG DISCOVERY; HEP G2 CELLS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MICROBIAL SENSITIVITY TESTS; REPLICON; RESPIRATORY SYNCYTIAL VIRUS INFECTIONS; RESPIRATORY SYNCYTIAL VIRUS, HUMAN; RNA REPLICASE; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 84964325481     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2016.03.015     Document Type: Article

References (22)

1. J. Chapman, E. Abbott, D.G. Alber, R.C. Baxter, S.K. Bithell, E.A. Henderson, M.C. Carter, P. Chambers, A. Chubb, G.S. Cockerill, and et al. RSV604, a novel inhibitor of respiratory syncytial virus replication Antimicrob. Agents Chemother. 51 2007 3346 3353
2. P.L. Collins, and J.A. Melero Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years Virus Res. 162 2011 80 99
3. P.L. Collins, R. Fearns, and B.S. Graham Respiratory syncytial virus: virology, reverse genetics, and pathogenesis of disease Curr. Top. Microbiol. Immunol. 372 2013 3 38
4. E. Comer, J.R. Duvall, and M.t duPont Lee Utilizing diversity-oriented synthesis in antimicrobial drug discovery Future Med. Chem. 6 2014 1927 1942
5. S. Dandapani, A.R. Germain, I. Jewett, S. le Quement, J.C. Marie, G. Muncipinto, J.R. Duvall, L.C. Carmody, J.R. Perez, J.C. Engel, and et al. Diversity-oriented synthesis yields a new drug lead for treatment of chagas disease ACS Med. Chem. Lett. 5 2014 149 153
6. R. Fearns, M.E. Peeples, and P.L. Collins Increased expression of the N protein of respiratory syncytial virus stimulates minigenome replication but does not alter the balance between the synthesis of mRNA and antigenome Virology 23 1997 188 201
7. R. Fearns, M.E. Peeples, and P.L. Collins Mapping the transcription and replication promoters of respiratory syncytial virus J. Virol. 76 2002 1663 1667
8. H. Grosfeld, M.G. Hill, and P.L. Collins RNA replication by respiratory syncytial virus (RSV) is directed by the N, P, and L proteins; transcription also occurs under these conditions but requires RSV superinfection for efficient synthesis of full-length mRNA J. Virol. 69 1995 5677 5686
9. C.B. Hall, G.A. Weinberg, A.K. Blumkin, K.M. Edwards, M.A. Staat, A.F. Schultz, K.A. Poehling, P.G. Szilagyi, M.R. Griffin, J.V. Williams, and et al. Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age Pediatrics 132 2013 e341 348
10. C.B. Hall, G.A. Weinberg, M.K. Iwane, A.K. Blumkin, K.M. Edwards, M.A. Staat, P. Auinger, M.R. Griffin, K.A. Poehling, D. Erdman, and et al. The burden of respiratory syncytial virus infection in young children N. Engl. J. Med. 360 2009 588 598
11. R.W. Heidebrecht Jr., C. Mulrooney, C.P. Austin, R.H. Barker Jr., J.A. Beaudoin, K.C. Cheng, E. Comer, S. Dandapani, J. Dick, J.R. Duvall, and et al. Diversity-oriented synthesis yields a novel lead for the treatment of malaria ACS Med. Chem. Lett. 3 2012 112 117
12. V.A. Laganas, E.F. Dunn, R.E. McLaughlin, C.L. Tiong-Yip, O. Yuzhakov, V.M. Isabella, P. Hill, and Q. Yu Characterization of novel respiratory syncytial virus inhibitors identified by high throughput screen Antivir. Res. 115 2015 71 74
13. O. Malykhina, M.A. Yednak, P.L. Collins, P.D. Olivo, and M.E. Peeples A respiratory syncytial virus replicon that is noncytotoxic and capable of long-term foreign gene expression J. Virol. 85 2011 4792 4801
14. C.A. Mulrooney, D.L. Lahr, M.J. Quintin, W. Youngsaye, D. Moccia, J.K. Asiedu, E.L. Mulligan, L.B. Akella, L.A. Marcaurelle, P. Montgomery, and et al. An informatic pipeline for managing high-throughput screening experiments and analyzing data from stereochemically diverse libraries J. Comput. aided Mol. Des. 27 2013 455 468
15. H. Nair, D.J. Nokes, B.D. Gessner, M. Dherani, S.A. Madhi, R.J. Singleton, K.L. O'Brien, A. Roca, P.F. Wright, N. Bruce, and et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis Lancet 375 2010 1545 1555
16. S.L. Noton, L.R. Deflube, C.Z. Tremaglio, and R. Fearns The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter PLoS Pathog. 8 2012 e1002980
17. S.L. Noton, W. Aljabr, J.A. Hiscox, D.A. Matthews, and R. Fearns Factors affecting de novo RNA synthesis and back-priming by the respiratory syncytial virus polymerase Virology 462-463 2014 318 327
18. S.L. Noton, K. Nagendra, E.F. Dunn, M.E. Mawhorter, Q. Yu, and R. Fearns Respiratory syncytial virus inhibitor Az-27 differentially inhibits different polymerase activities at the promoter J. Virol. 89 2015 7786 7798
19. H. Plant, C. Stacey, C.L. Tiong-Yip, J. Walsh, Q. Yu, and K. Rich High-throughput hit screening cascade to identify respiratory syncytial virus (RSV) inhibitors J. Biomol. Screen. 20 2015 597 605
20. E.A. Simoes, J.P. DeVincenzo, M. Boeckh, L. Bont, J.E. Crowe Jr., P. Griffiths, F.G. Hayden, R.L. Hodinka, R.L. Smyth, K. Spencer, and et al. Challenges and opportunities in developing respiratory syncytial virus therapeutics J. Infect. Dis. 211 Suppl. 1 2015 S1 S20
21. K. Sudo, Y. Miyazaki, N. Kojima, M. Kobayashi, H. Suzuki, M. Shintani, and Y. Shimizu YM-53403, a unique anti-respiratory syncytial virus agent with a novel mechanism of action Antivir. Res. 65 2005 125 131
22. C.L. Tiong-Yip, H. Plant, P. Sharpe, J. Fan, K. Rich, E. Gorseth, and Q. Yu Development of a high-throughput replicon assay for the identification of respiratory syncytial virus inhibitors Antivir. Res. 101 2014 75 81