1887

Chapter 29 : Antiviral Drugs

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Antiviral Drugs, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816698/9781555816032_Chap29-1.gif /docserver/preview/fulltext/10.1128/9781555816698/9781555816032_Chap29-2.gif

Abstract:

Although picornaviruses have an enormous impact on human health, the effective control of poliovirus (PV) and hepatitis A virus (HAV) infections with specific vaccines has largely restricted the search for antiviral drugs to those active in combating the common cold, caused by human rhinoviruses (HRVs). Today, there is growing interest in the development of antipicornavirus drugs for several reasons. Inhibitors of picornavirus replication that target different (structural as well as nonstructural) viral proteins have been reported during the last decades. This chapter presents an overview of the most relevant antipicornavirus compounds, according to their viral target. One of the earliest discovered classes of picornavirus inhibitors belongs to a series of compounds that were later designated WIN compounds, referring to Sterling-Winthrop, where they were developed. Several structural analogs of DPBR0Z-194 with enhanced antiviral activity were synthesized, including DBPR 103 and compound 28b, the latter being a highly selective inhibitor of enterovirus 71. A systematic evaluation of several reported HRV capsid-binding compounds active against all serotypes of HRV was performed by Andries. This study revealed the existence of two groups of HRVs, designated antiviral groups A and B. The activity of the gliotoxin compound was shown to be dependent on the presence of a disulfide bridge that is formed when the compound exists in its native oxidized state. For coxsackievirus, it was demonstrated that the in vitro efficacy of RNAi is highly dependent on two critical factors, namely, target selection and emergence of viral escape mutants.

Citation: De Palma A, Neyts J. 2010. Antiviral Drugs, p 461-482. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch29
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1.
Figure 1.

Schematic representation of the picornavirus replication cycle and possible targets for inhibition. Picornavirus inhibitors targeting both structural (VP1) and nonstructural viral proteins (3A, 2C, 3C, and 3D) have been reported. (Adapted from reference .)

Citation: De Palma A, Neyts J. 2010. Antiviral Drugs, p 461-482. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch29
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

Mode of action of capsid-binding compounds in HRV14. (Left) Schematic representation of binding between ICAM-1 (here simplified as a two-domain fragment) and major group HRV. ICAM-1 binds into the canyon, surrounding each 5-fold axis, inducing conformational changes that eventually lead to uncoating of the virus and release of the viral RNA. (Right) Binding of a WIN compound occurs in the interior hydrophobic pocket, located beneath the floor of the canyon. By occupying this pocket, (i) conformational changes occur in the floor of the pocket, hampering the ability of virions to interact with their receptor, and (ii) virion rigidity is increased, preventing uncoating of the virus and subsequent release of viral RNA. (Adapted from reference .)

Citation: De Palma A, Neyts J. 2010. Antiviral Drugs, p 461-482. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch29
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

Structural formulae of capsid-binding compounds. By binding into the hydrophobic pocket, located underneath the canyon floor, these compounds prevent cellular attachment, entry, and/or uncoating of the virus.

Citation: De Palma A, Neyts J. 2010. Antiviral Drugs, p 461-482. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch29
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4.
Figure 4.

Structural formulae of picornavirus inhibitors targeting the nonstructural protein 2C. All compounds interfere with viral replication and have been shown to select for resistance mutations in 2C.

Citation: De Palma A, Neyts J. 2010. Antiviral Drugs, p 461-482. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch29
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5.
Figure 5.

Structural formulae of picornavirus inhibitors that select for resistance mutations in the nonstructural protein 3A.

Citation: De Palma A, Neyts J. 2010. Antiviral Drugs, p 461-482. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch29
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.
Figure 6.

Structural formulae of picornavirus inhibitors targeting the viral RNA-dependent RNA polymerase 3D.

Citation: De Palma A, Neyts J. 2010. Antiviral Drugs, p 461-482. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch29
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 7.
Figure 7.

Structural formulae of protease inhibitors developed by Pfizer. These compounds interfere with the viral polyprotein processing steps by targeting the viral 3C protease.

Citation: De Palma A, Neyts J. 2010. Antiviral Drugs, p 461-482. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch29
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816698.ch29
1. AbuBakar, S.,, I. C. Sam,, J. Yusof,, M. K. Lim,, S. Misbah,, N. MatRahim, and, P. S. Hooi. 2009. Enterovirus 71 outbreak, Brunei. Emerg. Infect. Dis. 15:7982.
2. Abzug, M. J.,, G. Cloud,, J. Bradley,, P. J. Sanchez,, J. Romero,, D. Powell,, M. Lepow,, C. Mani,, E. V. Capparelli,, S. Blount,, F. Lakeman,, R. J. Whitley, and, D. W. Kimberlin. 2003. Double blind placebo-controlled trial of pleconaril in infants with enterovirus meningitis. Pediatr. Infect. Dis. J. 22:335341.
3. al Nakib, W.,, P. G. Higgins,, G. I. Barrow,, D. A. Tyrrell,, K. Andries,, G. Vanden Bussche,, N. Taylor, and, P. A. Janssen. 1989. Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837). Antimicrob. Agents Chemother. 33:522525.
4. Andries, K.,, B. Dewindt,, M. De Brabander,, R. Stokbroekx, and, P. A. Janssen. 1988. In vitro activity of R 61837, a new antirhinovirus compound. Arch. Virol. 101:155167.
5. Andries, K.,, B. Dewindt,, J. Snoeks, and, R. Willebrords. 1989. Lack of quantitative correlation between inhibition of replication of rhinoviruses by an antiviral drug and their stabilization. Arch. Virol. 106:5161.
6. Andries, K.,, B. Dewindt,, J. Snoeks,, R. Willebrords,, R. Stokbroekx, and, P. J. Lewi. 1991. A comparative test of fifteen compounds against all known human rhinovirus serotypes as a basis for a more rational screening program. Antivir. Res. 16:213225.
7. Andries, K.,, B. Dewindt,, J. Snoeks,, R. Willebrords,, K. van Eemeren,, R. Stokbroekx, and, P. A. Janssen. 1992. In vitro activity of pirodavir (R 77975), a substituted phenoxypyridazinamine with broad-spectrum antipicornaviral activity. Antimicrob. Agents Chemother. 36:100107.
8. Andries, K.,, B. Dewindt,, J. Snoeks,, L. Wouters,, H. Moereels,, P. J. Lewi, and, P. A. Janssen. 1990. Two groups of rhinoviruses revealed by a panel of antiviral compounds present sequence divergence and differential pathogenicity. J. Virol. 64:11171123.
9. Arita, M.,, T. Wakita, and, H. Shimizu. 2009. Cellular kinase inhibitors that suppress enterovirus replication have a conserved target in viral protein 3A similar to that of enviroxime. J. Gen. Virol. 90:18691879.
10. Arruda, E.,, C. E. Crump,, S. D. Marlin,, V. J. Merluzzi, and, F. G. Hayden. 1992. In vitro studies of the antirhinovirus activity of soluble intercellular adhesion molecule-1. Antimicrob. Agents Chemother. 36:11861191.
11. Aylward, R. B.,, R. W. Sutter, and, D. L. Heymann. 2005. Policy. OPV cessation: the final step to a “polio-free” world. Science 310:625626.
12. Badger, J.,, I. Minor,, M. J. Kremer,, M. A. Oliveira,, T. J. Smith,, J. P. Griffith,, D. M. Guerin,, S. Krishnaswamy,, M. Luo, and, M. G. Rossmann. 1988. Structural analysis of a series of antiviral agents complexed with human rhinovirus 14. Proc. Natl. Acad. Sci. USA 85:33043308.
13. Badger, J.,, I. Minor,, M. A. Oliveira,, T. J. Smith, and, M. G. Rossmann. 1989. Structural analysis of antiviral agents that interact with the capsid of human rhinoviruses. Proteins 6:119.
14. Baltera, R. F., Jr., and, D. R. Tershak. 1989. Guanidine-resistant mutants of poliovirus have distinct mutations in peptide 2C. J. Virol. 63:44414444.
15. Barnard, D. L. 2006. Current status of anti-picornavirus therapies. Curr. Pharm. Des. 12:13791390.
16. Barnard, D. L.,, V. D. Hubbard,, D. F. Smee,, R. W. Sidwell,, K. G. Watson,, S. P. Tucker, and, P. A. Reece. 2004. In vitro activity of expanded-spectrum pyridazinyl oxime ethers related to pirodavir: novel capsid-binding inhibitors with potent antipicornavirus activity. Antimicrob. Agents Chemother. 48:17661772.
17. Barton, D. J., and, J. B. Flanegan. 1997. Synchronous replication of poliovirus RNA: initiation of negative-strand RNA synthesis requires the guanidine-inhibited activity of protein 2C. J. Virol. 71:84828489.
18. Bergelson, J. M.,, J. A. Cunningham,, G. Droguett,, E. A. Kurt-Jones,, A. Krithivas,, J. S. Hong,, M. S. Horwitz,, R. L. Crowell, and, R. W. Finberg. 1997. Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science 275:13201323.
19. Bienz, K.,, D. Egger,, M. Troxler, and, L. Pasamontes. 1990. Structural organization of poliovirus RNA replication is mediated by viral proteins of the P2 genomic region. J. Virol. 64:11561163.
20. Binford, S. L.,, F. Maldonado,, M. A. Brothers,, P. T. Weady,, L. S. Zalman,, J. W. Meador III,, D. A. Matthews, and, A. K. Patick. 2005. Conservation of amino acids in human rhinovirus 3C protease correlates with broad-spectrum antiviral activity of rupintrivir, a novel human rhinovirus 3C protease inhibitor. Antimicrob. Agents Chemother. 49:619626.
21. Brown, R. N.,, R. Cameron,, D. K. Chalmers,, S. Hamilton,, A. Luttick,, G. Y. Krippner,, D. B. McConnell,, R. Nearn,, P. C. Stanislawski,, S. P. Tucker, and, K. G. Watson. 2005. 2-Ethoxybenzoxazole as a bioisosteric replacement of an ethyl benzoate group in a human rhinovirus (HRV) capsid binder. Bioorg. Med. Chem. Lett. 15:20512055.
22. Brown-Augsburger, P.,, L. M. Vance,, S. K. Malcolm,, H. Hsiung,, D. P. Smith, and, B. A. Heinz. 1999. Evidence that enviroxime targets multiple components of the rhinovirus 14 replication complex. Arch. Virol. 144:15691585.
23. Buontempo, P. J.,, S. Cox,, J. Wright-Minogue,, J. L. DeMartino,, A. M. Skelton,, E. Ferrari,, R. Albin,, E. J. Rozhon,, V. Girijavallabhan,, J. F. Modlin, and, J. F. O’Connell. 1997. SCH 48973:a potent, broad-spectrum, antienterovirus compound. Antimicrob. Agents Chemother. 41:12201225.
24. Caliguiri, L. A.,, J. J. McSharry, and, G. W. Lawrence. 1980. Effect of arildone on modifications of poliovirus in vitro. Virology 105:8693.
25. Caliguiri, L. A., and, I. Tamm. 1968. Action of guanidine on the replication of poliovirus RNA. Virology 35:408417.
26. Carrasco, L. 1994. Picornavirus inhibitors. Pharmacol. Ther. 64:215290.
27. Carroll, S. S.,, J. E. Tomassini,, M. Bosserman,, K. Getty,, M. W. Stahlhut,, A. B. Eldrup,, B. Bhat,, D. Hall,, A. L. Simcoe,, R. LaFemina,, C. A. Rutkowski,, B. Wolanski,, Z. Yang,, G. Migliaccio,, R. De Francesco,, L. C. Kuo,, M. MacCoss, and, D. B. Olsen. 2003. Inhibition of hepatitis C virus RNA replication by 2′-modified nucleoside analogs. J. Biol. Chem. 278:1197911984.
28. Casasnovas, J. M., and, T. A. Springer. 1995. Kinetics and thermodynamics of virus binding to receptor. Studies with rhinovirus, intercellular adhesion molecule-1 (ICAM-1), and surface plasmon resonance. J. Biol. Chem. 270:1321613224.
29. Caselli, A.,, G. Camici,, G. Manao,, G. Moneti,, L. Pazzagli,, G. Cappugi, and, G. Ramponi. 1994. Nitric oxide causes inactivation of the low molecular weight phosphotyrosine protein phosphatase. J. Biol. Chem. 269:2487824882.
30. Castrillo, J. L., and, L. Carrasco. 1987. Action of 3-methylquercetin on poliovirus RNA replication. J. Virol. 61:33193321.
31. Castrillo, J. L.,, D. Vanden Berghe, and, L. Carrasco. 1986. 3-Methylquercetin is a potent and selective inhibitor of polio-virus RNA synthesis. Virology 152:219227.
32. Chang, C. S.,, Y. T. Lin,, S. R. Shih,, C. C. Lee,, Y. C. Lee,, C. L. Tai,, S. N. Tseng, and, J. H. Chern. 2005. Design, synthesis, and antipicornavirus activity of 1-[5-(4-arylphenoxy)alkyl]-3-pyridin-4-ylimidazolidin-2-one derivatives. J. Med. Chem. 48:35223535.
33. Chapman, M. S.,, I. Minor,, M. G. Rossmann,, G. D. Diana, and, K. Andries. 1991. Human rhinovirus 14 complexed with antiviral compound R 61837. J. Mol. Biol. 217:455463.
34. Chen, T. C.,, H. Y. Chang,, P. F. Lin,, J. H. Chern,, J. T. Hsu,, C. Y. Chang, and, S. R. Shih. 2009. Novel antiviral agent DTriP-22 targets RNA-dependent RNA polymerase of enterovirus 71. Antimicrob. Agents Chemother. 53:27402747.
35. Chen, T. C.,, K. F. Weng,, S. C. Chang,, J. Y. Lin,, P. N. Huang, and, S. R. Shih. 2008. Development of antiviral agents for enteroviruses. J. Antimicrob. Chemother. 62:11691173.
36. Chern, J. H.,, C. C. Lee,, C. S. Chang,, Y. C. Lee,, C. L. Tai,, Y. T. Lin,, K. S. Shia,, C. Y. Lee, and, S. R. Shih. 2004. Synthesis and antienteroviral activity of a series of novel, oxime ether-containing pyridyl imidazolidinones. Bioorg. Med. Chem. Lett. 14:50515056.
37. Collett, M. S.,, J. Neyts, and, J. F. Modlin. 2008. A case for developing antiviral drugs against polio. Antivir. Res. 79:179187.
38. Colonno, R. J.,, P. L. Callahan, and, W. J. Long. 1986. Isolation of a monoclonal antibody that blocks attachment of the major group of human rhinoviruses. J. Virol. 57:712.
39. Cordingley, M. G.,, P. L. Callahan,, V. V. Sardana,, V. M. Garsky, and, R. J. Colonno. 1990. Substrate requirements of human rhinovirus 3C protease for peptide cleavage in vitro. J. Biol. Chem. 265:90629065.
40. Cory, A. H.,, T. C. Owen,, J. A. Barltrop, and, J. G. Cory. 1991. Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Commun. 3:207212.
41. Couzin, J. 2006. Report concludes polio drugs are needed, after disease is eradicated. Science 311:1539.
42. Cox, S.,, P. J. Buontempo,, J. Wright-Minogue,, J. L. DeMartino,, A. M. Skelton,, E. Ferrari,, J. Schwartz,, E. J. Rozhon,, C. C. Linn,, V. Girijavallabhan, and, J. F. O’Connell. 1996. Antipicornavirus activity of SCH 47802 and analogs: in vitro and in vivo studies. Antivir. Res. 32:7179.
43. Crowder, S., and, K. Kirkegaard. 2005. Trans-dominant inhibition of RNA viral replication can slow growth of drug-resistant viruses. Nat. Genet. 37:701709.
44. Crowell, R. L.,, A. K. Field,, W. A. Schleif,, W. L. Long,, R. J. Colonno,, J. E. Mapoles, and, E. A. Emini. 1986. Monoclonal antibody that inhibits infection of HeLa and rhabdomyosarcoma cells by selected enteroviruses through receptor blockade. J. Virol. 57:438445.
45. Crowther, D., and, J. L. Melnick. 1961. Studies of the inhibitory action of guanidine on poliovirus multiplication in cell cultures. Virology 15:6574.
46. Crump, C. E.,, E. Arruda, and, F. G. Hayden. 1994. Comparative antirhinoviral activities of soluble intercellular adhesion molecule-1 (sICAM-1) and chimeric ICAM-1/immunoglobulin A molecule. Antimicrob. Agents Chemother. 38:14251427.
47. Cushnie, T. P., and, A. J. Lamb. 2005. Antimicrobial activity of flavonoids. Int. J. Antimicrob. Agents 26:343356.
48. DeLong, D. C., and, S. E. Reed. 1980. Inhibition of rhinovirus replication in organ culture by a potential antiviral drug. J. Infect. Dis. 141:8791.
49. De Palma, A. M.,, W. Heggermont,, P. Leyssen,, G. Purstinger,, E. Wimmer,, E. De Clercq,, A. Rao,, A. M. Monforte,, A. Chimirri, and, J. Neyts. 2007. Anti-enterovirus activity and structure-activity relationship of a series of 2,6-dihalophenyl-substituted 1H,3H-thiazolo[3,4-a]benzimidazoles. Biochem. Biophys. Res. Commun. 353:628632.
50. De Palma, A. M.,, G. Puerstinger,, E. Wimmer,, A. K. Patick,, K. Andries,, B. Rombaut,, E. De Clercq, and, J. Neyts. 2008. Comparative activity of a selected series of anti-picornavirus compounds against poliovirus replication in vitro. Emerg. Infect. Dis. 14:545551.
51. De Palma, A. M.,, H. J. Thibaut,, L. L. van der,, K. Lanke,, W. Heggermont,, S. Ireland,, R. Andrews,, M. Arimilli,, T. H. Al Tel,, E. De Clercq,, F. van Kuppeveld, and, J. Neyts. 2009. Mutations in the nonstructural protein 3A confer resistance to the novel enterovirus replication inhibitor TTP-8307. Antimicrob. Agents Chemother. 53:18501857.
52. De Palma, A. M.,, I. Vliegen,, E. De Clercq, and, J. Neyts. 2008. Selective inhibitors of picornavirus replication. Med. Res. Rev. 28:823884.
53. De Palma, A. M.,, W. Heggermont,, K. Lanke,, B. Coutard,, M. Bergmann,, A. M. Monforte,, B. Canard,, E. De Clercq,, A. Chimirri,, G. Puerstinger,, J. Rohayem,, F. van Kuppeveld, and, J. Neyts. 2008. The thiazolobenzimidazole TBZE-029 inhibits enteroviral replication by targeting a short region immediately downstream motif C in the non-structural protein 2C. J. Virol. 82:47204730.
54. Diana, G. D.,, P. M. Carabateas,, R. E. Johnson,, G. L. Williams,, F. Pancic, and, J. C. Collins. 1978. Antiviral activity of some beta-diketones. 4. Benzyl diketones. In vitro activity against both RNA and DNA viruses. J. Med. Chem. 21:889894.
55. Diana, G. D.,, P. M. Carabateas,, U. J. Salvador,, G. L. Williams,, E. S. Zalay,, F. Pancic,, B. A. Steinberg, and, J. C. Collins. 1978. Antiviral activity of some beta-diketones. 3. Aryl bis(beta-diketones). Antiherpetic activity. J. Med. Chem. 21:689692.
56. Diana, G. D.,, M. A. McKinlay,, C. J. Brisson,, E. S. Zalay,, J. V. Miralles, and, U. J. Salvador. 1985. Isoxazoles with antipicornavirus activity. J. Med. Chem. 28:748752.
57. Diana, G. D.,, M. A. McKinlay,, M. J. Otto,, V. Akullian, and, C. Oglesby. 1985. [[(4,5-Dihydro-2-oxazolyl)phenoxy]alkyl] isoxazoles. Inhibitors of picornavirus uncoating. J. Med. Chem. 28:19061910.
58. Diana, G. D.,, P. Rudewicz,, D. C. Pevear,, T. J. Nitz,, S. C. Aldous,, D. J. Aldous,, D. T. Robinson,, T. Draper,, F. J. Dutko, and, C. Aldi. 1995. Picornavirus inhibitors: trifluoromethyl substitution provides a global protective effect against hepatic metabolism. J. Med. Chem. 38:13551371.
59. Diana, G. D.,, U. J. Salvador,, E. S. Zalay,, P. M. Carabateas,, G. L. Williams,, J. C. Collins, and, F. Pancic. 1977. Antiviral activity of some beta-diketones. 2. Aryloxy alkyl diketones. In vitro activity against both RNA and DNA viruses. J. Med. Chem. 20:757761.
60. Diana, G. D.,, U. J. Salvador,, E. S. Zalay,, R. E. Johnson,, J. C. Collins,, D. Johnson,, W. B. Hinshaw,, R. R. Lorenz,, W. H. Thiel-king, and, F. Pancic. 1977. Antiviral activity of some beta-diketones. 1. Aryl alkyl diketones. In vitro activity against both RNA and DNA viruses. J. Med. Chem. 20:750756.
61. Dragovich, P. S.,, T. J. Prins,, R. Zhou,, S. A. Fuhrman,, A. K. Patick,, D. A. Matthews,, C. E. Ford,, J. W. Meador III,, R. A. Ferre, and, S. T. Worland. 1999. Structure-based design, synthesis, and biological evaluation of irreversible human rhino-virus 3C protease inhibitors. 3. Structure-activity studies of ketomethylene-containing peptidomimetics. J. Med. Chem. 42:12031212.
62. Dragovich, P. S.,, T. J. Prins,, R. Zhou,, T. O. Johnson,, Y. Hua,, H. T. Luu,, S. K. Sakata,, E. L. Brown,, F. C. Maldonado,, T. Tuntland,, C. A. Lee,, S. A. Fuhrman,, L. S. Zalman,, A. K. Patick,, D. A. Matthews,, E. Y. Wu,, M. Guo,, B. C. Borer,, N. K. Nayyar,, T. Moran,, L. Chen,, P. A. Rejto,, P. W. Rose,, M. C. Guzman,, E. Z. Dovalsantos,, S. Lee,, K. McGee,, M. Mohajeri,, A. Liese,, J. Tao,, M. B. Kosa,, B. Liu,, M. R. Batugo,, J. P. Gleeson,, Z. P. Wu,, J. Liu,, J. W. Meador III, and, R. A. Ferre. 2003. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 8. Pharmacological optimization of orally bioavailable 2-pyridone-containing peptidomimetics. J. Med. Chem. 46:45724585.
63. Dragovich, P. S.,, T. J. Prins,, R. Zhou,, S. E. Webber,, J. T. Marakovits,, S. A. Fuhrman,, A. K. Patick,, D. A. Matthews,, C. A. Lee,, C. E. Ford,, B. J. Burke,, P. A. Rejto,, T. F. Hendrickson,, T. Tuntland,, E. L. Brown,, J. W. Meador III,, R. A. Ferre,, J. E. Harr,, M. B. Kosa, and, S. T. Worland. 1999. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 4. Incorporation of P1 lactam moieties as L-glutamine replacements. J. Med. Chem. 42:12131224.
64. Dragovich, P. S.,, S. E. Webber,, R. E. Babine,, S. A. Fuhrman,, A. K. Patick,, D. A. Matthews,, C. A. Lee,, S. H. Reich,, T. J. Prins,, J. T. Marakovits,, E. S. Littlefield,, R. Zhou,, J. Tikhe,, C. E. Ford,, M. B. Wallace,, J. W. Meador III,, R. A. Ferre,, E. L. Brown,, S. L. Binford,, J. E. Harr,, D. M. DeLisle, and, S. T. Worland. 1998. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structure-activity studies. J. Med. Chem. 41:28062818.
65. Dragovich, P. S.,, S. E. Webber,, R. E. Babine,, S. A. Fuhrman,, A. K. Patick,, D. A. Matthews,, S. H. Reich,, J. T. Marakovits,, T. J. Prins,, R. Zhou,, J. Tikhe,, E. S. Littlefield,, T. M. Bleckman,, M. B. Wallace,, T. L. Little,, C. E. Ford,, J. W. Meador III,, R. A. Ferre,, E. L. Brown,, S. L. Binford,, D. M. DeLisle, and, S. T. Worland. 1998. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 2. Peptide structure-activity studies. J. Med. Chem. 41:28192834.
66. Dragovich, P. S.,, S. E. Webber,, T. J. Prins,, R. Zhou,, J. T. Marakovits,, J. G. Tikhe,, S. A. Fuhrman,, A. K. Patick,, D. A. Matthews,, C. E. Ford,, E. L. Brown,, S. L. Binford,, J. W. Meador III,, R. A. Ferre, and, S. T. Worland. 1999. Structure-based design of irreversible, tripeptidyl human rhinovirus 3C protease inhibitors containing N-methyl amino acids. Bioorg. Med. Chem. Lett. 9:21892194.
67. Dragovich, P. S.,, R. Zhou,, S. E. Webber,, T. J. Prins,, A. K. Kwok,, K. Okano,, S. A. Fuhrman,, L. S. Zalman,, F. C. Maldonado,, E. L. Brown,, J. W. Meador III,, A. K. Patick,, C. E. Ford,, M. A. Brothers,, S. L. Binford,, D. A. Matthews,, R. A. Ferre, and, S. T. Worland. 2000. Structure-based design of ketone-containing, tripeptidyl human rhinovirus 3C protease inhibitors. Bioorg. Med. Chem. Lett. 10:4548.
68. Eggers, H. J., and, I. Tamm. 1961. Spectrum and characteristics of the virus inhibitory action of 2-(alphahydroxybenzyl)-benz imidazole. J. Exp. Med. 113:657682.
69. Eggers, H. J., and, I. Tamm. 1962. On the mechanism of a selective inhibition of enterovirus multiplication by 2-(alpha-hydroxybenzyl)-benzimidazole. Virology 18:426438.
70. Eggers, H. J., and, I. Tamm. 1963. Inhibition of enterovirus ribonucleic acid synthesis by 2-(alpha-hydroxy-benzyl)-benzimidazole. Nature 197:13271328.
71. Evans, D. J., and, J. W. Almond. 1998. Cell receptors for picornaviruses as determinants of cell tropism and pathogenesis. Trends Microbiol. 6:198202.
72. Fang, F., and, M. Yu. 2004. Viral receptor blockage by multiva-lent recombinant antibody fusion proteins: inhibiting human rhinovirus (HRV) infection with CFY196. J. Antimicrob. Chemother. 53:2325.
73. Fechner, H.,, I. Sipo,, D. Westermann,, S. Pinkert,, X. Wang,, L. Suckau,, J. Kurreck,, H. Zeichhardt,, O. Muller,, R. Vetter,, V. Erd-mann,, C. Tschope, and, W. Poller. 2008. Cardiac-targeted RNA interference mediated by an AAV9 vector improves cardiac function in coxsackievirus B3 cardiomyopathy. J. Mol. Med. 86:987997.
74. Florea, N. R.,, D. Maglio, and, D. P. Nicolau. 2003. Pleconaril, a novel antipicornaviral agent. Pharmacotherapy 23:339348.
75. Gerzon, K.,, C. Ryan, and, D. DeLong. 1974. Method of virus suppression by hydantoins. U.S. patent 3,790,6733.
76. Gitlin, L.,, S. Karelsky, and, R. Andino. 2002. Short interfering RNA confers intracellular antiviral immunity in human cells. Nature 418:430434.
77. Gitlin, L.,, J. K. Stone, and, R. Andino. 2005. Poliovirus escape from RNA interference: short interfering RNA-target recognition and implications for therapeutic approaches. J. Virol. 79:10271035.
78. Golde, W. T.,, J. M. Pacheco,, H. Duque,, T. Doel,, B. Penfold,, G. S. Ferman,, D. R. Gregg, and, L. L. Rodriguez. 2005. Vaccination against foot-and-mouth disease virus confers complete clinical protection in 7 days and partial protection in 4 days: use in emergency outbreak response. Vaccine 23:57755782.
79. Goris, N.,, A. De Palma,, J. F. Toussaint,, I. Musch,, J. Neyts, and, K. De Clercq. 2006. 2′-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus. Antivir. Res. 73:161168
80. Graci, J. D.,, K. Too,, E. D. Smidansky,, J. P. Edathil,, E. W. Barr,, D. A. Harki,, J. E. Galarraga,, J. M. Bollinger, Jr.,, B. R. Peterson,, D. Loakes,, D. M. Brown, and, C. E. Cameron. 2008. Lethal mutagenesis of picornaviruses with N-6-modified purine nucleoside analogues. Antimicrob. Agents Chemother. 52:971979.
81. Greve, J. M.,, C. P. Forte,, C. W. Marlor,, A. M. Meyer,, H. Hoover-Litty,, D. Wunderlich, and, A. McClelland. 1991. Mechanisms of receptor-mediated rhinovirus neutralization defined by two soluble forms of ICAM-1. J. Virol. 65:60156023.
82. Griffiths, E.,, D. Wood, and, L. Barreto. 2006. Polio vaccine: the first 50 years and beyond. Biologicals 34:7374.
83. Grubman, M. J., and, B. Baxt. 2004. Foot-and-mouth disease. Clin. Microbiol. Rev. 17:465493.
84. Hadaschik, D.,, M. Klein,, H. Zimmermann,, H. J. Eggers, and, B. Nelsen-Salz. 1999. Dependence of echovirus 9 on the enterovirus RNA replication inhibitor 2-(alpha-hydroxybenzyl)-w protein 2C. J. Virol. 73:1053610539.
85. Hamdouchi, C.,, J. de Blas,, M. del Prado,, J. Gruber,, B. A. Heinz, and, L. Vance. 1999. 2-Amino-3-substituted-6-[(E)-1-phenyl-2-(N-methylcarbamoyl)vinyl]imidazo[1,2-a]pyridines as a novel class of inhibitors of human rhinovirus: stereospecific synthesis and antiviral activity. J. Med. Chem. 42:5059.
86. Hamdouchi, C.,, J. Ezquerra,, J. A. Vega,, J. J. Vaquero,, J. Alvarez-Builla, and, B. A. Heinz. 1999. Short synthesis and anti-rhinoviral activity of imidazo[1,2-a]pyridines: the effect of acyl groups at 3-position. Bioorg. Med. Chem. Lett. 9:13911394.
87. Hannon, G. J. 2002. RNA interference. Nature 418:244251.
88. Hanzlik, R. P., and, S. A. Thompson. 1984. Vinylogous amino acid esters: a new class of inactivators for thiol proteases. J. Med. Chem. 27:711712.
89. Harki, D. A.,, J. D. Graci,, J. E. Galarraga,, W. J. Chain,, C. E. Cameron, and, B. R. Peterson. 2006. Synthesis and antiviral activity of 5-substituted cytidine analogues: identification of a potent inhibitor of viral RNA-dependent RNA polymerases. J. Med. Chem. 49:61666169.
90. Harrison, D. N.,, E. V. Gazina,, D. F. Purcell,, D. A. Anderson, and, S. Petrou. 2008. Amiloride derivatives inhibit coxsackievirus B3 RNA replication. J. Virol. 82:14651473.
91. Hayden, F. G.,, K. Andries, and, P. A. Janssen. 1992. Safety and efficacy of intranasal pirodavir (R77975) in experimental rhinovirus infection. Antimicrob. Agents Chemother. 36:727732.
92. Hayden, F. G., and, J. M. Gwaltney, Jr. 1982. Prophylactic activity of intranasal enviroxime against experimentally induced rhinovirus type 39 infection. Antimicrob. Agents Chemother. 21:892897.
93. Hayden, F. G.,, J. M. Gwaltney, Jr., and, R. J. Colonno. 1988. Modification of experimental rhinovirus colds by receptor blockade. Antivir. Res. 9:233247.
94. Hayden, F. G.,, D. T. Herrington,, T. L. Coats,, K. Kim,, E. C. Cooper,, S. A. Villano,, S. Liu,, S. Hudson,, D. C. Pevear,, M. Collett, and, M. McKinlay. 2003. Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials. Clin. Infect. Dis. 36:15231532.
95. Hayden, F. G.,, G. J. Hipskind,, D. H. Woerner,, G. F. Eisen,, M. Janssens,, P. A. Janssen, and, K. Andries. 1995. Intranasal pirodavir (R77,975) treatment of rhinovirus colds. Antimicrob. Agents Chemother. 39:290294.
96. Hayden, F. G.,, R. B. Turner,, J. M. Gwaltney,, K. Chi-Burris,, M. Gersten,, P. Hsyu,, A. K. Patick,, G. J. Smith III, and, L. S. Zalman. 2003. Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers. Antimicrob. Agents Chemother. 47:39073916.
97. Heinz, B. A., and, L. M. Vance. 1995. The antiviral compound enviroxime targets the 3A coding region of rhinovirus and poliovirus. J. Virol. 69:41894197.
98. Heinz, B. A., and, L. M. Vance. 1996. Sequence determinants of 3A-mediated resistance to enviroxime in rhinoviruses and enteroviruses. J. Virol. 70:48544857.
99. Herrmann, E. C., Jr.,, J. A. Herrmann, and, D. C. DeLong. 1982. Prevention of death in mice infected with coxsackievirus A16 using guanidine HCl mixed with substituted benzimidazoles. Antivir. Res. 2:339346.
100. Hershenson, M. B., and, S. L. Johnston. 2006. Rhinovirus infections: more than a common cold. Am. J. Respir. Crit. Care Med. 174:12841285.
101. Higgins, P. G.,, G. I. Barrow,, W. al Nakib,, D. A. Tyrrell,, D. C. DeLong, and, I. Lenox-Smith. 1988. Failure to demonstrate synergy between interferon-alpha and a synthetic antiviral, enviroxime, in rhinovirus infections in volunteers. Antivir. Res. 10:141149.
102. Hsyu, P. H.,, Y. K. Pithavala,, M. Gersten,, C. A. Penning, and, B. M. Kerr. 2002. Pharmacokinetics and safety of an antirhinoviral agent, ruprintrivir, in healthy volunteers. Antimicrob. Agents Chemother. 46:392397.
103. Ishitsuka, H.,, C. Ohsawa,, T. Ohiwa,, I. Umeda, and, Y. Suhara. 1982. Antipicornavirus flavone RO 09-0179. Antimicrob. Agents Chemother. 22:611616.
104. Johnson, T. O.,, Y. Hua,, H. T. Luu,, E. L. Brown,, F. Chan,, S. S. Chu,, P. S. Dragovich,, B. W. Eastman,, R. A. Ferre,, S. A. Fuhrman,, T. F. Hendrickson,, F. C. Maldonado,, D. A. Matthews,, J. W. Meador III,, A. K. Patick,, S. H. Reich,, D. J. Skalitzky,, S. T. Worland,, M. Yang, and, L. S. Zalman. 2002. Structure-based design of a parallel synthetic array directed toward the discovery of irreversible inhibitors of human rhinovirus 3C protease. J. Med. Chem. 45:20162023.
105. Kaiser, L.,, C. E. Crump, and, F. G. Hayden. 2000. In vitro activity of pleconaril and AG7088 against selected serotypes and clinical isolates of human rhinoviruses. Antivir. Res. 47:215220.
106. Kaldor, S. W.,, M. Hammond,, B. A. Dressman,, J. Labus,, F. Chadwell,, A. D. Kline, and, B. A. Heinz. 1995. Glutamine-derived aldehydes for the inhibition of human rhinovirus 3C protease. Bioorg. Med. Chem. Lett. 5:20212026.
107. Kim, K. H.,, P. Willingmann,, Z. X. Gong,, M. J. Kremer,, M. S. Chapman,, I. Minor,, M. A. Oliveira,, M. G. Rossmann,, K. Andries, and, G. D. Diana. 1993. A comparison of the anti-rhinoviral drug binding pocket in HRV14 and HRV1A. J. Mol. Biol. 230:206227.
108. Kim, S. S.,, T. J. Smith,, M. S. Chapman,, M. C. Rossmann,, D. C. Pevear,, F. J. Dutko,, P. J. Felock,, G. D. Diana, and, M. A. McKinlay. 1989. Crystal structure of human rhinovirus sero-type 1A (HRV1A). J. Mol. Biol. 210:91111.
109. Klein, M.,, H. J. Eggers, and, B. Nelsen-Salz. 1999. Echovirus 9 strain Barty non-structural protein 2C has NTPase activity. Virus Res. 65:155160.
110. Klein, M.,, D. Hadaschik,, H. Zimmermann,, H. J. Eggers, and, B. Nelsen-Salz. 2000. The picornavirus replication inhibitors HBB and guanidine in the echovirus-9 system: the significance of viral protein 2C. J. Gen. Virol. 81:895901.
111. Kong, J. S.,, S. Venkatraman,, K. Furness,, S. Nimkar,, T. A. Shepherd,, Q. M. Wang,, J. Aube, and, R. P. Hanzlik. 1998. Synthesis and evaluation of peptidyl Michael acceptors that inactivate human rhinovirus 3C protease and inhibit virus replication. J. Med. Chem. 41:25792587.
112. Kuz’min, V. E.,, A. G. Artemenko,, E. N. Muratov,, I. L. Volineckaya,, V. A. Makarov,, O., B. Riabova,, P. Wutzler, and, M. Schmidtke. 2007. Quantitative structure-activity relationship studies of [(biphenyloxy)propyl]isoxazole derivatives. Inhibitors of human rhinovirus 2 replication. J. Med. Chem. 50:42054213.
113. Lall, M. S.,, R. P. Jain, and, J. C. Vederas. 2004. Inhibitors of 3C cysteine proteinases from Picornaviridae. Curr. Top. Med. Chem. 4:12391253.
114. Langford, M. P.,, W. A. Ball, and, J. P. Ganley. 1995. Inhibition of the enteroviruses that cause acute hemorrhagic conjunctivitis (AHC) by benzimidazoles: enviroxime (LY 122772) and enviradone (LY 127123). Antivir. Res. 27:355365.
115. Larin, N. M.,, M. P. Copping,, R. H. Herbst-Laier,, B. Roberts, and, R. B. Wenham. 1965. Antiviral activity of gliotoxin. Chemotherapy 10:1223.
116. Lawson, M. A., and, B. L. Semler. 1990. Picornavirus protein processing: enzymes, substrates, and genetic regulation. Curr. Top. Microbiol. Immunol. 161:4987.
117. Lentz, K. N.,, A. D. Smith,, S. C. Geisler,, S. Cox,, P. Buontempo,, A. Skelton,, J. DeMartino,, E. Rozhon,, J. Schwartz,, V. Girijavallabhan,, J. O’Connell, and, E. Arnold. 1997. Structure of poliovirus type 2 Lansing complexed with antiviral agent SCH48973: comparison of the structural and biological properties of three poliovirus serotypes. Structure 5:961978.
118. Levandowski, R. A.,, C. T. Pachucki,, M. Rubenis, and, G. G. Jackson. 1982. Topical enviroxime against rhinovirus infection. Antimicrob. Agents Chemother. 22:10041007.
119. Liu, S., and, R. P. Hanzlik. 1992. Structure-activity relationships for inhibition of papain by peptide Michael acceptors. J. Med. Chem. 35:10671075.
120. Loddo, B.,, W. Ferrari,, G. Brotzu, and, A. Spanedda. 1962. In vitro inhibition of infectivity of polio viruses by guanidine. Nature 193:9798.
121. Lu, W. W.,, Y. Y. Hsu,, J. Y. Yang, and, S. H. Kung. 2004. Selective inhibition of enterovirus 71 replication by short hairpin RNAs. Biochem. Biophys. Res. Commun. 325:494499.
122. MacLennan, C.,, G. Dunn,, A. P. Huissoon,, D. S. Kumararatne,, J. Martin,, P. O’Leary,, R. A. Thompson,, H. Osman,, P. Wood,, P. Minor,, D. J. Wood, and, D. Pillay. 2004. Failure to clear persistent vaccine-derived neurovirulent poliovirus infection in an immunodeficient man. Lancet 363:15091513.
123. Makarov, V. A.,, O. B. Riabova,, V. G. Granik,, P. Wutzler, and, M. Schmidtke. 2005. Novel [(biphenyloxy)propyl]isoxazole derivatives for inhibition of human rhinovirus 2 and coxsackievirus B3 replication. J. Antimicrob. Chemother. 55:483488.
124. Malcolm, B. A.,, C. Lowe,, S. Shechosky,, R. T. McKay,, C. C. Yang,, V. J. Shah,, R. J. Simon,, J. C. Vederas, and, D. V. Santi. 1995. Peptide aldehyde inhibitors of hepatitis A virus 3C proteinase. Biochemistry 34:81728179.
125. Mallia, P.,, M. Contoli,, G. Caramori,, A. Pandit,, S. L. Johnston, and, A. Papi. 2007. Exacerbations of asthma and chronic obstructive pulmonary disease (COPD): focus on virus induced exacerbations. Curr. Pharm. Des. 13:7397.
126. Mallia, P., and, S. L. Johnston. 2006. How viral infections cause exacerbation of airway diseases. Chest 130:12031210.
127. Marlin, S. D.,, D. E. Staunton,, T. A. Springer,, C. Stratowa,, W. Sommergruber, and, V. J. Merluzzi. 1990. A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection. Nature 344:7072.
128. Martinez, J.,, A. Patkaniowska,, H. Urlaub,, R. Luhrmann, and, T. Tuschl. 2002. Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell 110:563574.
129. Matthews, D. A.,, P. S. Dragovich,, S. E. Webber,, S. A. Fuhrman,, A. K. Patick,, L. S. Zalman,, T. F. Hendrickson,, R. A. Love,, T. J. Prins,, J. T. Marakovits,, R. Zhou,, J. Tikhe,, C. E. Ford,, J. W. Meador,, R. A. Ferre,, E. L. Brown,, S. L. Binford,, M. A. Brothers,, D. M. DeLisle, and, S. T. Worland. 1999. Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes. Proc. Natl. Acad. Sci. USA 96:1100011007.
130. McKinlay, M. A. 1985. WIN 51711, a new systematically active broad- spectrum antipicornavirus agent. J. Antimicrob. Chemother. 16:284286.
131. McKinlay, M. A.,, J. V. Miralles,, C. J. Brisson, and, F. Pancic. 1982. Prevention of human poliovirus-induced paralysis and death in mice by the novel antiviral agent arildone. Antimicrob. Agents Chemother. 22:10221025.
132. McManus, T. E.,, A. M. Marley,, N. Baxter,, S. N. Christie,, H. J. O’Neill,, J. S. Elborn,, P. V. Coyle, and, J. C. Kidney. 2008. Respiratory viral infection in exacerbations of COPD. Respir. Med. 102:15751580.
133. McSharry, J. J.,, L. A. Caliguiri, and, H. J. Eggers. 1979. Inhibition of uncoating of poliovirus by arildone, a new antiviral drug. Virology 97:307315.
134. Mendelsohn, C. L.,, E. Wimmer, and, V. R. Racaniello. 1989. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell 56:855865.
135. Merl, S.,, C. Michaelis,, B. Jaschke,, M. Vorpahl,, S. Seidl, and, R. Wessely. 2005. Targeting 2A protease by RNA interference attenuates coxsackieviral cytopathogenicity and promotes survival in highly susceptible mice. Circulation 111:15831592.
136. Merl, S., and, R. Wessely. 2007. Anti-coxsackieviral efficacy of RNA interference is highly dependent on genomic target selection and emergence of escape mutants. Oligonucleotides 17:4453.
137. Miller, F. D.,, A. S. Monto,, D. C. DeLong,, A. Exelby,, E. R. Bryan, and, S. Srivastava. 1985. Controlled trial of enviroxime against natural rhinovirus infections in a community. Antimicrob. Agents Chemother. 27:102106.
138. Miller, P. A.,, K. P. Milstrey, and, P. W. Trown. 1968. Specific inhibition of viral ribonucleic acid replication by gliotoxin. Science 159:431432.
139. Moeremans, M.,, M. De Raeymaeker,, G. Daneels,, M. De Brabander,, F. Aerts,, C. Janssen, and, K. Andries. 1992. Study of the parameters of binding of R 61837 to human rhinovirus 9 and immunobiochemical evidence of capsid-stabilizing activity of the compound. Antimicrob. Agents Chemother. 36:417424.
140. Murray, M. A.,, J. W. Janc,, S. Venkatraman, and, L. M. Babe. 2001. Peptidyl diazomethyl ketones inhibit the human rhinovirus 3C protease: effect on virus yield by partial block of P3 polyprotein processing. Antivir. Chem. Chemother. 12:273281.
141. Ninomiya, Y.,, M. Aoyama,, I. Umeda,, Y. Suhara, and, H. Ishitsuka. 1985. Comparative studies on the modes of action of the antirhinovirus agents Ro 09-0410, Ro 09-0179, RMI-15,731, 4′,6-dichloroflavan, and enviroxime. Antimicrob. Agents Chemother. 27:595599.
142. Nygardas, M.,, T. Vuorinen,, A. P. Aalto,, D. H. Bamford, and, V. Hukkanen. 2009. Inhibition of coxsackievirus B3 and related enteroviruses by antiviral siRNA pools produced using phi6 RNA-dependent RNA polymerase. J. Gen. Virol. 90:24682473.
143. Oberste, M. S.,, D. Moore,, B. Anderson,, M. A. Pallansch,, D. C. Pevear, and, M. S. Collett. 2009. In vitro antiviral activity of V-073 against polioviruses. Antimicrob. Agents Chemother. 53:45014503.
144. Ohlin, A.,, H. Hoover-Litty,, G. Sanderson,, A. Paessens,, S. L. Johnston,, S. T. Holgate,, E. Huguenel, and, J. M. Greve. 1994. Spectrum of activity of soluble intercellular adhesion molecule-1 against rhinovirus reference strains and field isolates. Antimicrob. Agents Chemother. 38:14131415.
145. Oren, D. A.,, A. Zhang,, H. Nesvadba,, B. Rosenwirth, and, E. Arnold. 1996. Synthesis and activity of piperazine-containing antirhinoviral agents and crystal structure of SDZ 880-061 bound to human rhinovirus 14. J. Mol. Biol. 259:120134.
146. Patick, A. K. 2006. Rhinovirus chemotherapy. Antivir. Res. 71:391396.
147. Patick, A. K.,, S. L. Binford,, M. A. Brothers,, R. L. Jackson,, C. E. Ford,, M. D. Diem,, F. Maldonado,, P. S. Dragovich,, R. Zhou,, T. J. Prins,, S. A. Fuhrman,, J. W. Meador,, L. S. Zalman,, D. A. Matthews, and, S. T. Worland. 1999. In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease. Antimicrob. Agents Chemother. 43:24442450.
148. Patick, A. K.,, M. A. Brothers,, F. Maldonado,, S. Binford,, O. Maldonado,, S. Fuhrman,, A. Petersen,, G. J., Smith III,, L. S. Zalman,, L. A. Burns-Naas, and, J. Q. Tran. 2005. In vitro antiviral activity and single-dose pharmacokinetics in humans of a novel, orally bioavailable inhibitor of human rhinovirus 3C protease. Antimicrob. Agents Chemother. 49:22672275.
149. Pevear, D. C.,, M. J. Fancher,, P. J. Felock,, M. G. Rossmann,, M. S. Miller,, G. Diana,, A. M. Treasurywala,, M. A. McKinlay, and, F. J. Dutko. 1989. Conformational change in the floor of the human rhinovirus canyon blocks adsorption to HeLa cell receptors. J. Virol. 63:20022007.
150. Pevear, D. C.,, T. M. Tull,, M. E. Seipel, and, J. M. Groarke. 1999. Activity of pleconaril against enteroviruses. Antimicrob. Agents Chemother. 43:21092115.
151. Pfister, T., and, E. Wimmer. 1999. Characterization of the nucleoside triphosphatase activity of poliovirus protein 2C reveals a mechanism by which guanidine inhibits poliovirus replication. J. Biol. Chem. 274:69927001.
152. Phillpotts, R. J.,, R. W. Jones,, D. C. DeLong,, S. E. Reed,, J. Wallace, and, D. A. Tyrrell. 1981. The activity of enviroxime against rhinovirus infection in man. Lancet i:13421344.
153. Phillpotts, R. J.,, J. Wallace,, D. A. Tyrrell, and, V. B. Tagart. 1983. Therapeutic activity of enviroxime against rhinovirus infection in volunteers. Antimicrob. Agents Chemother. 23:671675.
154. Phipps, K. M.,, A. Martinez,, J. Lu,, B. A. Heinz, and, G. Zhao. 2004. Small interfering RNA molecules as potential antihuman rhinovirus agents: in vitro potency, specificity, and mechanism. Antivir. Res. 61:4955.
155. Pincus, S. E.,, D. C. Diamond,, E. A. Emini, and, E. Wimmer. 1986. Guanidine-selected mutants of poliovirus: mapping of point mutations to polypeptide 2C. J. Virol. 57:638646.
156. Pincus, S. E.,, H. Rohl, and, E. Wimmer. 1987. Guanidine-dependent mutants of poliovirus: identification of three classes with different growth requirements. Virology 157:8388.
157. Pincus, S. E., and, E. Wimmer. 1986. Production of guanidine-resistant and -dependent poliovirus mutants from cloned cDNA: mutations in polypeptide 2C are directly responsible for altered guanidine sensitivity. J. Virol. 60:793796.
158. Pritchard, J. F.,, M. Jurima-Romet,, M. L. Reimer,, E. Mortimer,, B. Rolfe, and, M. N. Cayen. 2003. Making better drugs: decision gates in non-clinical drug development. Nat. Rev. Drug Discov. 2:542553.
159. Qiu, J. 2008. Enterovirus 71 infection: a new threat to global public health? Lancet Neurol. 7:868869.
160. Rightsel, W. A.,, J. R. Dice,, R. J. McAlpine,, E. A. Timm,, I. W. McLean, Jr.,, G. J. Dixon, and, F. M. Schabel, Jr. 1961. Antiviral effect of guanidine. Science 134:558559.
161. Rodriguez, P. L., and, L. Carrasco. 1992. Gliotoxin: inhibitor of poliovirus RNA synthesis that blocks the viral RNA polymerase 3Dpol. J. Virol. 66:19711976.
162. Rodriguez, P. L., and, L. Carrasco. 1993. Poliovirus protein 2C has ATPase and GTPase activities. J. Biol. Chem. 268:81058110.
163. Rollinger, J. M.,, T. M. Steindl,, D. Schuster,, J. Kirchmair,, K. Anrain,, E. P. Ellmerer,, T. Langer,, H. Stuppner,, P. Wutzler, and, M. Schmidtke. 2008. Structure-based virtual screening for the discovery of natural inhibitors for human rhinovirus coat protein. J. Med. Chem. 51:842851.
164. Rosenwirth, B.,, Z. L. Kis, and, H. J. Eggers. 1995. In vivo efficacy of SDZ 35-682, a new picornavirus capsid-binding agent. Antivir. Res. 26:5564.
165. Rosenwirth, B.,, D. A. Oren,, E. Arnold,, Z. L. Kis, and, H. J. Eggers. 1995. SDZ 35-682, a new picornavirus capsid-binding agent with potent antiviral activity. Antivir. Res. 26:6582.
166. Rossmann, M. G. 1989. The canyon hypothesis. Viral Immunol. 2:143161.
167. Rossmann, M. G. 1989. The structure of antiviral agents that inhibit uncoating when complexed with viral capsids. Antivir. Res. 11:313.
168. Rossmann, M. G.,, E. Arnold,, J. W. Erickson,, E. A., Frankenberger, J. P. Griffith,, H. J. Hecht,, J. E. Johnson,, G. Kamer,, M. Luo, and, A. G. Mosser. 1985. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317:145153.
169. Rotbart, H. A., and, A. D. Webster. 2001. Treatment of potentially life-threatening enterovirus infections with pleconaril. Clin. Infect. Dis. 32:228235.
170. Rozhon, E.,, S. Cox,, P. Buontempo,, J. O’Connell,, W. Slater,, J. De Martino,, J. Schwartz,, G. Miller,, E. Arnold, and, A. Zhang. 1993. SCH 38057:a picornavirus capsid-binding molecule with antiviral activity after the initial stage of viral uncoating. Antivir. Res. 21:1535.
171. Saunders, K., and, A. M. King. 1982. Guanidine-resistant mutants of aphthovirus induce the synthesis of an altered non-structural polypeptide, P34. J. Virol. 42:389394.
172. Saunders, K.,, A. M. King,, D. McCahon,, J. W. Newman,, W. R. Slade, and, S. Forss. 1985. Recombination and oligonucleotide analysis of guanidine-resistant foot-and-mouth disease virus mutants. J. Virol. 56:921929.
173. Sawyer, M. H. 2002. Enterovirus infections: diagnosis and treatment. Semin. Pediatr. Infect. Dis. 13:4047.
174. Senior, K. 2002. FDA panel rejects common cold treatment. Lancet Infect. Dis. 2:264.
175. Shepherd, T. A.,, G. A. Cox,, E. McKinneay,, T. Tang,, M. Wakulchick,, R. E. Zimmerman, and, E. C. Villarreal. 1996. Small peptidic aldehyde inhibitors of human rhinovirus 3C protease. Bioorg. Med. Chem. Lett. 6:28932896.
176. Shia, K. S.,, W. T. Li,, C. M. Chang,, M. C. Hsu,, J. H. Chern,, M. K. Leong,, S. N. Tseng,, C. C. Lee,, Y. C. Lee,, S. J. Chen,, K. C. Peng,, H. Y. Tseng,, Y. L. Chang,, C. L. Tai, and, S. R. Shih. 2002. Design, synthesis, and structure-activity relationship of pyridyl imidazolidinones: a novel class of potent and selective human enterovirus 71 inhibitors. J. Med. Chem. 45:16441655.
177. Shih, S. R.,, M. C. Tsai,, S. N. Tseng,, K. F. Won,, K. S. Shia,, W. T. Li,, J. H. Chern,, G. W. Chen,, C. C. Lee,, Y. C. Lee,, K. C. Peng, and, Y. S. Chao. 2004. Mutation in enterovirus 71 capsid protein VP1 confers resistance to the inhibitory effects of pyridyl imidazolidinone. Antimicrob. Agents Chemother. 48:35233529.
178. Shimizu, H.,, M. Agoh,, Y. Agoh,, H. Yoshida,, K. Yoshii,, T. Yoneyama,, A. Hagiwara, and, T. Miyamura. 2000. Mutations in the 2C region of poliovirus responsible for altered sensitivity to benzimidazole derivatives. J. Virol. 74:41464154.
179. Siegl, G., and, H. J. Eggers. 1982. Failure of guanidine and 2-(alpha-hydroxybenzyl)benzimidazole to inhibit replication of hepatitis A virus in vitro. J. Gen. Virol. 61:111114.
180. Sim, A. C.,, A. Luhur,, T. M. Tan,, V. T. Chow, and, C. L. Poh. 2005. RNA interference against enterovirus 71 infection. Virology 341:7279.
181. Smith, T. J.,, M. J. Kremer,, M. Luo,, G. Vriend,, E. Arnold,, G. Kamer,, M. G. Rossmann,, M. A. McKinlay,, G. D. Diana, and, M. J. Otto. 1986. The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating. Science 233:12861293.
182. Staunton, D. E.,, V. J. Merluzzi,, R. Rothlein,, R. Barton,, S. D. Marlin, and, T. A. Springer. 1989. A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses. Cell 56:849853.
183. Steindl, T. M.,, C. E. Crump,, F. G. Hayden, and, T. Langer. 2005. Pharmacophore modeling, docking, and principal component analysis based clustering: combined computer-assisted approaches to identify new inhibitors of the human rhinovirus coat protein. J. Med. Chem. 48:62506260.
184. Tan, E. L.,, K. F. Marcus, and, C. L. Poh. 2008. Development of RNA interference (RNAi) as potential antiviral strategy against enterovirus 70. J. Med. Virol. 80:10251032.
185. Tan, E. L.,, T. M. Tan,, T. K. Chow, and, C. L. Poh. 2007. Inhibition of enterovirus 71 in virus-infected mice by RNA interference. Mol. Ther. 15:19311938.
186. Tershak, D. R. 1982. Inhibition of poliovirus polymerase by guanidine in vitro. J. Virol. 41:313318.
187. Thompson, D.,, P. Muriel,, D. Russell,, P. Osborne,, A. Bromley,, M. Rowland,, S. Creigh-Tyte, and, C. Brown. 2002. Economic costs of the foot and mouth disease outbreak in the United Kingdom in 2001. Rev. Sci. Tech. 21:675687.
188. Tolskaya, E. A.,, L. I. Romanova,, M. S. Kolesnikova,, A. P. Gmyl,, A. E. Gorbalenya, and, V. I. Agol. 1994. Genetic studies on the poliovirus 2C protein, an NTPase. A plausible mechanism of guanidine effect on the 2C function and evidence for the importance of 2C oligomerization. J. Mol. Biol. 236:13101323.
189. Tomassini, J. E.,, D. Graham,, C. M. DeWitt,, D. W. Lineberger,, J. A. Rodkey, and, R. J. Colonno. 1989. cDNA cloning reveals that the major group rhinovirus receptor on HeLa cells is intercellular adhesion molecule 1. Proc. Natl. Acad. Sci. USA 86:49074911.
190. Trown, P. W., and, J. A. Bilello. 1972. Mechanism of action of gliotoxin: elimination of activity by sulfhydryl compounds. Antimicrob. Agents Chemother. 2:261266.
191. Turner, R. B.,, M. T. Wecker,, G. Pohl,, T. J. Witek,, E. McNally,, R. St. George,, B. Winther, and, F. G. Hayden. 1999. Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial. JAMA 281:17971804.
192. Vance, L. M.,, N. Moscufo,, M. Chow, and, B. A. Heinz. 1997. Poliovirus 2C region functions during encapsidation of viral RNA. J. Virol. 71:87598765.
193. Van Hoof, L.,, D. A. Vanden Berghe,, G. M. Hatfield, and, A. J. Vlietinck. 1984. Plant antiviral agents. V. 3-Methoxyflavones as potent inhibitors of viral-induced block of cell synthesis. Planta Med. 50:513517.
194. Venkatraman, S.,, J. Kong,, S. Nimkar,, Q. M. Wang,, J. Aube, and, R. P. Hanzlik. 1999. Design, synthesis, and evaluation of azapeptides as substrates and inhibitors for human rhinovirus 3C protease. Bioorg. Med. Chem. Lett. 9:577580.
195. Verlinden, Y.,, A. Cuconati,, E. Wimmer, and, B. Rombaut. 2000. The antiviral compound 5-(3,4-dichlorophenyl) methylhydantoin inhibits the post-synthetic cleavages and the assembly of poliovirus in a cell-free system. Antivir. Res. 48:6169.
196. Victor, F.,, T. J. Brown,, K. Campanale,, B. A. Heinz,, L. A. Shipley,, K. S. Su,, J. Tang,, L. M. Vance, and, W. A. Spitzer. 1997. Synthesis, antiviral activity, and biological properties of vinylacetylene analogs of enviroxime. J. Med. Chem. 40:15111518.
197. Victor, F.,, R. Loncharich,, J. Tang, and, W. A. Spitzer. 1997. Synthesis and antiviral activity of C2 analogs of enviroxime: an exploration of the role of critical functionality. J. Med. Chem. 40:34783483.
198. Wang, Q. M., and, S. H. Chen. 2007. Human rhinovirus 3C protease as a potential target for the development of antiviral agents. Curr. Protein Pept. Sci. 8:1927.
199. Wang, Q. M.,, R. B. Johnson,, L. N. Jungheim,, J. D. Cohen, and, E. C. Villarreal. 1998. Dual inhibition of human rhinovirus 2A and 3C proteases by homophthalimides. Antimicrob. Agents Chemother. 42:916920.
200. Watson, K. G.,, R. N. Brown,, R. Cameron,, D. K. Chalmers,, S. Hamilton,, B. Jin,, G. Y. Krippner,, A. Luttick,, D. B. McConnell,, P. A. Reece,, J. Ryan,, P. C. Stanislawski,, S. P. Tucker,, W. Y. Wu,, D. L. Barnard, and, R. W. Sidwell. 2003. An orally bioavailable oxime ether capsid binder with potent activity against human rhinovirus. J. Med. Chem. 46:31813184.
201. Webber, S. E.,, J. T. Marakovits,, P. S. Dragovich,, T. J. Prins,, R. Zhou,, S. A. Fuhrman,, A. K. Patick,, D. A. Matthews,, C. A. Lee,, B. Srinivasan,, T. Moran,, C. E. Ford,, M. A. Brothers,, J. E. Harr,, J. W. Meador III,, R. A. Ferre, and, S. T. Worland. 2001. Design and synthesis of irreversible depsipeptidyl human rhinovirus 3C protease inhibitors. Bioorg. Med. Chem. Lett. 11:26832686.
202. Webber, S. E.,, K. Okano,, T. L. Little,, S. H. Reich,, Y. Xin,, S. A. Fuhrman,, D. A. Matthews,, R. A. Love,, T. F. Hendrickson,, A. K. Patick,, J. W. Meador III,, R. A. Ferre,, E. L. Brown,, C. E. Ford,, S. L. Binford, and, S. T. Worland. 1998. Tripeptide aldehyde inhibitors of human rhinovirus 3C protease: design, synthesis, biological evaluation, and cocrystal structure solution of P1 glutamine isosteric replacements. J. Med. Chem. 41:27862805.
203. Wikel, J. H.,, C. J. Paget,, D. C. DeLong,, J. D. Nelson,, C. Y. Wu,, J. W. Paschal,, A. Dinner,, R. J. Templeton,, M. O. Chaney,, N. D. Jones, and, J. W. Chamberlin. 1980. Synthesis of syn and anti isomers of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-benzimidaz-ol-2-amine. Inhibitors of rhinovirus multiplication. J. Med. Chem. 23:368372.
204. Witherell, G. 2000. AG-7088. Pfizer. Curr. Opin. Investig. Drugs 1:297302.
205. Woods, M. G.,, G. D. Diana,, M. C. Rogge,, M. J. Otto,, F. J. Dutko, and, M. A. McKinlay. 1989. In vitro and in vivo activities of WIN 54954, a new broad-spectrum antipicornavirus drug. Antimicrob. Agents Chemother. 33:20692074.
206. Wu, Z.,, Y. Gao,, L. Sun,, P. Tien, and, Q. Jin. 2008. Quick identification of effective small interfering RNAs that inhibit the replication of coxsackievirus A16. Antivir. Res. 80:295301.
207. Xian, M.,, Q. M. Wang,, X. Chen,, K. Wang, and, P. G. Wang. 2000. S-Nitrosothiols as novel, reversible inhibitors of human rhinovirus 3C protease. Bioorg. Med. Chem. Lett. 10:20972100.
208. Yang, F.,, L. Ren,, Z. Xiong,, J. Li,, Y. Xiao,, R. Zhao,, Y. He,, G. Bu,, S. Zhou,, J. Wang, and, J. Qi. 2009. Enterovirus 71 outbreak in the People’s Republic of China in 2008. J. Clin. Microbiol. 47:23512352.
209. Yang, P. C.,, R. M. Chu,, W. B. Chung, and, H. T. Sung. 1999. Epidemiological characteristics and financial costs of the 1997 foot-and-mouth disease epidemic in Taiwan. Vet. Rec. 145:731734.
210. Yuan, J.,, P. K. Cheung,, H. M. Zhang,, D. Chau, and, D. Yang. 2005. Inhibition of coxsackievirus B3 replication by small interfering RNAs requires perfect sequence match in the central region of the viral positive strand. J. Virol. 79:21512159.
211. Zhang, A.,, R. G. Nanni,, T. Li,, G. F. Arnold,, D. A. Oren,, A. Jacobo-Molina,, R. L. Williams,, G. Kamer,, D. A. Rubenstein, and, Y. Li. 1993. Structure determination of antiviral compound SCH 38057 complexed with human rhinovirus 14. J. Mol. Biol. 230:857867.
212. Zhang, K. E.,, B. Hee,, C. A. Lee,, B. Liang, and, B. C. Potts. 2001. Liquid chromatography-mass spectrometry and liquid chromatography-NMR characterization of in vitro metabolites of a potent and irreversible peptidomimetic inhibitor of rhinovirus 3C protease. Drug Metab. Dispos. 29:729734.