Chapter 18 : Development of Antiviral Agents for Picornavirus Infections

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The discovery and development of antiviral agents for the treatment of picornavirus infections have been the focus of extensive research for more than 50 years. This chapter discusses the pharmaceutical advantages of newer molecules with respect to drug development. In reviewing the historical progression toward potent picornavirus antiviral agents, two classes of inhibitors (interferon and capsid-binding molecules) stand out as having demonstrated efficacy in clinical trials of picornavirus infections. This chapter reviews the activities of these agents and their corresponding clinical data. A discussion of problems in the further development of antipicornavirus agents is also presented in this chapter. Experimental approaches to modulation of enteroviral infections have included research on chemotherapy, monoclonal antibodies, vaccines, interferons, and capsid-binding agents. Several factors appear to correlate with the abilities of a compound to bind to the drugbinding pocket and to manifest antiviral activity. Examples of the potential influence of these parameters on compound binding and antiviral activity are discussed in this chapter. The chapter talks about mechanism of viral inhibition by capsid-binding molecules, preclinical biology of capsidbinding molecules, and clinical studies with capsidbinding molecules. The majority of molecules studied have limited solubility in aqueous environments. Significant progress has been made in the discovery and development of chemotherapeutic agents for picornaviruses.

Citation: O'Connell J, Albin R, Blum D, Grint P, Schwartz J. 1995. Development of Antiviral Agents for Picornavirus Infections, p 419-434. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch18
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Induction of 2′,5′-adenylate synthetase system by viral infection. Infection of HeLa cells with encephalomyocarditis (EMC) virus results in formation of double-stranded RNA (dsRNA), which has a dual activity: it activates 2',5'-adenylate synthetase and results in the production of interferon. The appearance of 2'5'(A)n induces RNase L, which degrades incoming viral RNA, probably at the poly(A) 3' terminus. Interferon induces 2',5'-adenyIate synthetase in adjacent cells, inducing the cascade, which then prevents incoming EMC virus from replicating in the adjacent cell. The figure is based on studies by Hearl and Johnston ( ) and Gribaudo et al. ( ).

Citation: O'Connell J, Albin R, Blum D, Grint P, Schwartz J. 1995. Development of Antiviral Agents for Picornavirus Infections, p 419-434. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch18
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Image of FIGURE 2

Chemical structures of representative picornavirus capsid binding inhibitors

Citation: O'Connell J, Albin R, Blum D, Grint P, Schwartz J. 1995. Development of Antiviral Agents for Picornavirus Infections, p 419-434. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch18
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Image of FIGURE 3

Binding of SCH 38057 to HRV14. Atoms of SCH 38057 are indicated by colored spheres. The main chain of VPl is indicated by ribbons. Conformational changes induced by SCH 38057 are indicated as follows: blue, no significant conformational shifts in these residues; yellow, main chain shifts less than 0.5 Å (0.05 nm); pink, main chain shifts less than 1.0 Å (0.1 nm); red, main chain shifts more than 1.0 Å (0.1 nm). Selected pocket residues are indicated in white. (From Zhang et al., [ ].)

Citation: O'Connell J, Albin R, Blum D, Grint P, Schwartz J. 1995. Development of Antiviral Agents for Picornavirus Infections, p 419-434. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch18
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Image of FIGURE 4

Schematic diagram of SCH 38057 in the hydrophobic pocket of HRV14 VP1. SCH 38057 is located in the innermost end of the pocket and leaves a large open space near the entrance of the pocket. This is in contrast to WIN compounds ( ) andjanssen R61837 ( ), which occupy the space nearest the entrance and leave open space in the innermost portion of the pocket. (Derived from Zhang et al.[ ].)

Citation: O'Connell J, Albin R, Blum D, Grint P, Schwartz J. 1995. Development of Antiviral Agents for Picornavirus Infections, p 419-434. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch18
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Comparison of conformational shifts in the HRV14 VP1 region upon binding of SCH 38057 andWIN 51711. Displacements of C-alpha atoms relative to the native HRV14 coordinates are shown as dots. Changes in the βC and βD strands are similar in the two compounds. However, changes in the βD, βF, and βG strands in the SCH 38057 complex are not reported in theWIN 51711 studies with HRV14. (Derived from Zhang et al. [ ].)

Citation: O'Connell J, Albin R, Blum D, Grint P, Schwartz J. 1995. Development of Antiviral Agents for Picornavirus Infections, p 419-434. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch18
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1. Alacron, B.,, A. Zerial,, C. Dupiol,, and L. Carrasco. 1986. Antirhinovirus compound 44 081 R.P. inhibits virus uncoating. Antimicrob. Agents Chemother. 30: 31 34.
2. Al-Nakib, W.,, R. G. Higgins,, G. I. Barrow,, D. A. J. Tyrrell,, K. Andries,, G. Vanden Bussche,, N. Taylor,, and R. A. J. Janssen. 1989. Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837). Antimicrob. Agents Chemother. 33: 522 525.
3. Andrei, G. M.,, O. I. Pieroni,, H. S. Gatica,, and C. E. Coto. 1985. Substituted benzalde-hyde thiosemicarbazone with antiviral activity against picornavirus. Drugs Exp. Clin. Res. 12: 869 873.
4. Andries, K.,, B. Dewindt,, M. De Brabander,, R. Stokbroekx,, and R. A. J. Janssen. 1988. In vitro activity of R61837, a new rhinovirus compound. Arch. Virol. 101: 155 167.
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. Virology 106: 51 61.
6. Andries, K.,, B. Dewindt,, J. Snoeks,, R. Willebrords,, K. Van Eemeren,, R. Stokbroekx,, and R. A. J. Janssen. 1992. In vitro activity of pirodavir (R 77975), a substituted phenoxy-pyridazinamine with broad-spectrum antipicornaviral activity. Antimicrob. Agents Chemother. 36: 100 107.
7. Andries, K.,, B. Dewindt,, J. Snoeks,, L. Wouters,, H. Moereels,, R. J. Lewi,, and R. A. J. Janssen. 1990. Two groups of rhinoviruses revealed by a panel of antiviral compounds present sequence divergence and differential pathogenicity. J. Virol. 64: 1117 1123.
8. Badger, J.,, I. Minor,, M. J. Kremer,, M. A. Oliveira,, T. J. Smith,, J. R Griffith,, D. M. A. Guerin,, S. Krishnaswamy,, M. Luo,, M. G. Rossmann,, M. A. McKinlay,, G. D. Diana,, R. J. Dutko,, M. Fancher,, R. R. Rueckert,, and B. A. Heinz. 1988. Structural analysis of a series of antiviral agents complexed with human rhinovirus 14. Proc. Natl. Acad. Sci. USA 85: 3304 3308.
9. Barrera-Oro, J. G.,, and J. L. Melnick. 1961. The effect of guanidine. I. On the experimental poliomyelitis induced by oral administration of virus to cynomolgous monkeys. II. On naturally occurring enterovirus of cynomolgous monkeys. Tex. Rep. Biol. Med. 19: 529 536.
10. Barrow, G. I.,, R. G. Higgins,, D. A. J. Tyrrell,, and K. Andries. 1990. An appraisal of the efficacy of the antiviral R 61837 in rhinovirus infections in human volunteers. Antiviral Chem. Chemother. 5: 279 283.
11. Bergelson, J. M.,, M. R Shepley,, B. M. C. Chan,, M. E. Hemler,, and R. W. Finberg. 1992. Identification of the integrin VLA-2 as a receptor for echovirus 1. Science 255: 1718 1720.
12. Capobianchi, M. R.,, D. Matteucci,, A. Giovannetti,, E. Soldaini,, M. Bendinelli,, J. G. Stanton,, and F. Dianzani. 1991. Role of interferon in lethality and lymphoid atrophy induced by coxsackievirus B3 infection in mice. Virol. Immunol. 5: 103 110.
13. Centers for Disease Control. 1989. Enterovirus surveillance—United States 1989. Morbid. Mortal. Weekly Rep. 38: 563.
14. Centers for Disease Control. 1991. Aseptic meningitis—New York State and United States, weeks 1-36, Morbid. Mortal. Weekly Rep. 40: 773775.
15. 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: 455 463.
16. Chonmaitree, T.,, and S. Baron. 1991. Bacteria and viruses induce production of interferon in the cerebrospinal fluid of children with acute meningitis: a study of 57 cases and review. Rev. Infect. Dis. 13: 1061 1065.
17. Crowell, R. L.,, D. L. Krah,, J. Mapoles,, and B.J. Landau. 1983. Methods of assay of cellular receptors for picornaviruses. Methods Enzymol. 96: 443 452.
18. Dagan, R.,, C. B. Hall,, K. R. Powell,, and M. A. Menegus. 1989. Epidemiology and laboratory diagnosis of infection with viral and bacterial pathogens in infants hospitalized for suspected sepsis. J. Pediatr. 115: 351 356.
19. Diana, G. D.,, M. A. McKinlay,, C. J. Brisson,, £. S. Zalay,, J. V. Miralles,, and U. J. Salvador. 1985. Isoxazoles with anti-picornavirus activity. J. Med. Chem. 28: 748 752.
20. Douglas, R. M.,, B. W. Moore,, H. B. Miles,, L. M. Davies,, N. Graham,, P. Ryan,, D. Worswick,, and J. Albricht. 1986. Prophylactic efficacy of intranasal alpha A2-interferon against rhinovirus infections in the family setting. N. Engl. J. Med. 314: 65 70.
21.Drugs and Market Development. 1992. Hepatitis A vaccine development. Drugs Market Dev. 3: 8690.
22. Dubois, M. R.,, and A. G. Hovanessian. 1990. Modified subcellular localization of interferon induced p68 kinase during encephalo-myocarditis virus infection. Virology 179: 591 598.
23. Eggers, H. J. 1985. Antiviral agents against picornaviruses. Antiviral Res. Suppl. 1: 57 65.
24. Eggers, H. J.,, M. A. Koch,, A. Furst,, G. D. Daves, Jr.,, J. J. Wilczynski,, and K. Folkers. 1970. Rhodanine: a selective inhibitor of the multiplication of echovirus 12. Science 167: 294 297.
25. Eggers, H. J.,, and I. Tamm. 1966. Antiviral chemotherapy. Annu. Rev. Pharmacol. 6: 231 250.
26. Enders, J. F.,, T. H. Weller,, and F. C. Robbtns. 1949. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science 109: 85 87.
27. Fox, J. P.,, M. K. Cooney,, C. E. Hall,, and H. M. Foy. 1985. Rhinoviruses in Seattle families, 1975-1979. Am. J. Epidemiol. 122: 830 846.
28. Fox, M. P.,, M. A. McKinlay,, G. D. Diana,, and F. J. Dutko. 1991. Binding affinities of structurally related human rhinovirus capsid-binding compounds are related to their activities against human rhinovirus type \ 4. Antimicrob. Agents Chemother. 35: 1040 1047.
29. Fox, P. M.,, M. J. Otto,, and M. A. McKinlay. 1986. Prevention of rhinovirus and poliovirus uncoating by WIN 51711, a new antiviral drug. Antimicrob. Agents Chemother. 30: 110 116.
30. Fuyinami, R. S.,, A. Rosenthal,, P. W. Lampert,, A. Zurhriggen,, and M. Yamada. 1989. Survival of athymic (nu/nu) mice after Theiler's murine encephalomyelitis virus infection by passive administration of neutralizing monoclonal antibody. J. Virol. 63: 2081 2087.
31. Geniteau-Legendre, M.,, F. Forestier,, A. M. Quero,, and A. German. 1987. Role of interferon, antibodies and macrophages in the protective effect of Corynebacterium parvum on encephalomyocarditis virus-induced disease in mice. Antiviral Res. 7: 161 167.
32. Greenberg, S. B.,, M. W. Harmon,, R. B. Couch,, P. E. Johnson,, S. Z. Wilson,, C. C. Dacso,, K. Bloom,, and J. Quarles. 1982. Prophylactic effect of low doses of human leukocyte interferon against infection with rhinovirus. J. Infect. Dis. 145: 542 546.
33. Greve, J. M.,, G. Davis,, A. M. Meyer,, C. P. Forte,, S. C. Yost,, C. W. Marlor,, M. E. Kamarck,, and A. McClelland. 1989. The major human rhinovirus receptor is ICAM-1. Cell 56: 839 847.
34. Gribaudo, G.,, D. Lembo,, G. Cavallo,, S. Landolfo,, and P. Lengyl. 1991. Interferon action: binding of viral RNA to the 40 kilodalton 2',5'-oligoadenylate synthetase in in-terferon-treated HeLa cells infected with the encephalomyocarditis virus. J. Virol. 65: 1748 1757.
35. Hayden, R.,, J. K. Albrecht,, D. L. Kaiser,, and J. M. Gwaltney. 1986. Prevention of natural colds by contact prophylaxis with intranasal alpha2-interferon. N. Engl. J. Med. 314: 71 75.
36. Hayden, E.,, and J. M. Gwaltney. 1983. Intranasal interferon alpha2 for prevention of rhinovirus infection and illness. J. Infect. Dis. 148: 543 550.
37. Hayden, R.,, and J. M. Gwaltney. 1984. Intranasal interferon-a2 treatment of experimental rhinoviral colds. J. Infect. Dis. 150: 174 180.
38. Hayden, F. G.,, A. Andries,, and P. A. J. Janssen. 1992. Safety and efficacy of intranasal pirodavir (R77975) in experimental rhinovirus infection. Antimicrob. Agents Chemother. 36: 727 732.
39. Hearl, W. G.,, and M. I. Johnston. 1987. Accumulation of 2\5'-oligoadenylates in encephalomyocarditis virus-infected mice. J. Virol, 61: 1586 1592.
40. Heinz, B. A., 1990. Escape mutant analysis of a drug-binding site can be used to map functions in the rhinovirus capsid, p. 173 186. In W. G. Laver, and G. M. Air (ed.), Use of X-Ray Crystallography in the Design of Antiviral Agents. Academic Press, Inc., San Diego, Calif.
41. Heinz, B. A.,, R. R. Rueckert,, D. A. Shepard,, F. J. Dutko,, M. A. McKinlay,, M. Fancher,, M. G. Rossmann,, J. Badger,, and T. J. Smith. 1989. Genetic and molecular analysis of spontaneous mutants of human rhinovirus 14 that are resistant to an antiviral compound., J. Virol. 63: 2476 2485.
42. Higgins, P. G.,, G. I. Barrow,, and D. A. Tyrrell. 1990. A study of the efficacy of the bradykinin antagonist, NPC 567, in rhinovirus infections in human volunteers. Antiviral Res. 14: 339 344.
43. Higgins, P. G.,, P. J. Scott,, P. M. Daniels,, and D. R. Gamble. 1974. A comparative study of viruses associated with acute hemorrhagic conjunctivitis. _ J. Clin. Pathol. 27: 292 296.
44. Hogle, J. M.,, M. Chow,, and D. J. Filman. 1985. Three-dimensional structure of poliovirus at 2.9 A resolution. Science 229: 1358 1365.
45. Hsia, J.,, A. Goldstein,, G. Simon,, M. Sztein,, and F. Hayden. 1990. Peripheral blood mononuclear cell interleukin-2 and interferon production, cytotoxicity, and antigen-stimulated blastogenesis during experimental rhinovirus infection. J. Infect. Dis. 162: 591 597.
46. Hsu, K.-H. L.,, K. Lonberg-Holm,, B. Alstein,, and R. L. Crowell. 1988. A monoclonal antibody specific for the cellular receptor for the group B coxsackieviruses. J. Virol. 62: 1647 1652.
47. Ichimura, H.,, K. Shimase,, I. Tamura,, E. Kaneto,, O. Kurimura,, Y. Aramitsu,, and T. Kurimura. 1985. Neutralizing antibody and interferon-alpha in cerebrospinal fluids and sera of acute aseptic meningitis. J. Med. Virol. 15: 231 237.
48. Ishitsuka, H.,, C. Ohsawa,, T. Ohiwa,, I. Umeda,, and Y. Suhara. 1982. Antipicornavirus flavone Ro 09-0179. Antimicrob. Agents Chemother. 22: 611 616.
49. Jordan, G.W. andV. Bolton. 1985. Interferon-sensitive Coxsackie virus variants in nature. J. Interferon Res. 5: 289 296.
50. Kandolf, R.,, A. Canu,, and P. H. Hofschneider. 1985. Coxsackie B3 virus can replicate in cultured human foetal heart cells and is inhibited by interferon. J. Mol. Cell. Cardiol. 17: 167 181.
51. Kenny, M. T.,, J. K. Dulworth,, T. M. Bargar,, and J. K. Daniel. 1987. Antipicornavirus activity of some diaryl methanes and aralkylamino-pyridines. Antiviral Res. 7: 87 97.
52. Kenny, M. T.,, J. K. Dulworth,, and H. L. Torney. 1985. In vitro and in vivo antipicornavirus activity of some phenoxypyridine-carbonitriles. Antimicrob. Agents Chemother. 28: 745 750.
53. Kishimoto, C.,, C. S. Crumpacker,, and W. H. Abelmann. 1988. Prevention of murine coxsackie B3 viral myocarditis and associated lymphoid organ atrophy with recombinant human leucocyte interferon alpha A/D. Cardiovasc. Res. 22: 732 738.
54. Kuhrt, M. E.,, M. J. Fancher,, V. Jasty,, F. Pancic,, and P. E. Came. 1979. Preliminary studies of the mode of action of arildone, a novel antiviral agent. Antimicrob. Agents Chemother. 15: 813 819.
55. Langford, M. P.,, J. C. Barber,, V. E. Sklar,, S. W. Clark III,, P. A. Patriarca,, I. M. Onarato,, M. Yin-Murphy,, and G. J. Stanton. 1985. Virus-specific, early appearing neutralizing activity and interferon production in patients with acute hemorrhagic conjunctivitis. Cwrr. Eye Res. 4: 233 239.
56. Langford, M. P.,, D. J. Carr,, and M. Yin-Murphy. 1985. Activity of arildone with or without interferon against acute hemorrhagic conjunctivitis viruses in cell culture. Antimicrob. Agents Chemother. 28: 578 580.
57. Langford, M. P.,, R. M. Kadi,, J. P. Ganley,, and M. Yin-Murphy. 1988. Inhibition of epidemic isolates of coxsackie virus type A24 by recombinant and natural interferon alpha and interferon beta. Intervirology 29: 320 327.
58. Levandowski, R.,, and D. Horohov. 1991. Rhinovirus induces natural killer-like cytotoxic cells and interferon alpha in mononuclear leukocytes. J. Med. Virol. 35: 116 120.
59. Levandowski, R.,, C. T. Pachucki,, M. Rubenis,, and G. G. Jackson. 1982. Topical enviroxime against rhinovirus infection. Antimicrob. Agents Chemother. 22: 1004 1007.
60. Levin, S.,, E. Leibowitz,, J. Torten,, and T. Hahn. 1989. Interferon treatment in acute progressive and fulminant hepatitis. Isr.J. Med. Sci. 25: 364 372.
61. Lopez-Guerrero, J. A.,, F. X. Pimentel-Muinos,, M. Fresno,, and M. A. Alonso. 1990. Role of soluble cytokines on the restricted replication of poliovirus in the monocytic U937 cell line. Virus Res. 16: 225 230.
62. Matsumori, A.,, N. Tomika,, and C. Kawai. 1988. Protective effect of recombinant alpha interferon on coxsackievirus B3 myocarditis in mice. Am. Heart J. 115: 1229 1232.
63. Matsumori, A.,, H. Wang,, W. H. Abelmann,, and C. S. Crumpacker. 1985. Treatment of viral myocarditis with ribavirin in an animal preparation. Circulation 71: 834 839.
64. McKinlay, M. A.,, and B. A. Steinberg. 1986. Oral efficacy of WIN 51711 in mice infected with human poliovirus. Antimicrob. Agents Chemother. 29: 30 32.
65. McKinney, R. I.,, S. L. Katz,, and C. M. Wilfert. 1987. Chronic enteroviral meningoencephalitis in agammaglobulin patients. Rev. Infect. Dis. 9: 334 356.
66. McSharry, J. J.,, L. A. Caliguiri,, and H. J. Eggers. 1979. Inhibition of uncoating of poliovirus by arildone, a new antiviral drug. Virology 97: 307 315.
67. Melnick, J. L., 1990. Enteroviruses: polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses, p. 549 605. In B. N. Fields, and D. M. Knipe (ed.), Virology. Raven Press Ltd., New York.
68. Melnick, J. L.,, D. Cronither,, and J. Barrera-Oro. 1961. Rapid development of drug resistant mutants of poliovirus. Science 134: 551 552.
69. Mendelsohn, C.,, 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: 855 865.
70. Merigan, T.,, S. Reed,, T. Hall,, and D. Tyrrell. 1973. Inhibition of respiratory virus infection by locally applied interferon. Lancet i: 536 567.
71. Meurs, E.,, D. Krause,, N. Robert,, R. H. Silverman,, and A. G. Hovanessian. 1985. The 2-5A system in control and interferon-treated K/BALB cells infected with enceph-alomyocarditis virus. Prog. Clin. Biol. Res. 202: 307 315.
72. Modlin, J. F., 1990. Coxsackievirus, echovirus and newer enteroviruses, p. 1367 1383. In G. L. Mandell,, R. G. Douglas, Jr.,, and J. E. Bennet (ed.), Principles and Practice of Infectious Disease. Churchill Livingstone, Inc., New York.
73. Monto, A. S.,, E. R. Bryan,, and S. Ohmit. 1987. Rhinovirus infections inTecumseh, Michigan: frequency of illness and number of serotypes. J. Infect. Dis. 156: 43 49.
74. Morrissey, L. M.,, and K. Kirkegaard. 1991. Regulation of a double-stranded RNA modification activity in human cells. Mol. Cell. Biol. 11: 3719 3725.
75. Naclerio, R. M.,, D. Proud,, L. M. Lichtenstein,, A. Kagey-Sobotka,, J. Hendley,, J. Sorrentino,, and J. M. Gwaltney. 1988. Kinins are generated during experimental colds. J. Infect. Dis. 157: 133 142.
76. 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 enviro-xime. Antimicrob. Agents Chemother. 27: 595 599.
77. Okada, I.,, A. Matsumori,, Y. Matoba,, M. Tominaga,, T. Yamada,, and C. Kowai. 1992. Combination treatment with ribavirin and interferon for coxsackievirus B3 replication.J. Lab. Clin. Med. 120: 569 573.
78. Otto, M. J.,, M. P. Fox,, M. J. Fancher,, M. F. Kuhrt,, G. D. Diana,, and M. A. McKinlay. 1985. In vitro activity of WIN 51711, a new broad-spectrum antipicornavirus drug. Antimicrob. Agents Chemother. 27: 883 886.
79. 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: 2002 2007.
80. Pitkaranta, A.,, K. Linnavouri,, and T. Houi. 1991. Virus-induced interferon production in human leukocytes: a low responder to one virus can be a high responder to another virus. J. Interferon Res. 11: 17 23.
81. Rombaut, B.,, R. Vrijsen,, and A. Boeye. 1985. Comparison of arildone and 3-methylquercetin as stabilizers of poliovirus. Antiviral Res. Suppl. 1: 67 73.
82. Rossmann, M. G. 1989. The structure of antiviral agents that inhibit uncoating when complexed with viral capsids. Antiviral Res. 11: 314.
83. Rotbart, H. A., 1989. Human enterovirus infections: molecular approaches to diagnosis and pathogenesis, p. 243 264. In B. L. Semler, and E. Ehrenfeld (ed.), Molecular Aspects of Picornavirus Infection and Detection. American Society for Microbiology, Washington, D.C.
84. Rozhon, E.,, S. Cox,, P. Buontempo,, J. O'Connell,, W. Slater,, J. DeMartino,, J. Schwartz,, G. Miller,, E. Arnold,, A. Zhang,, C. Morrow,, S. Jablonski,, P. Pinto,, R. Verace,, T. Duelfer, and V Girijavallabhan. 1993. SCH 38057: a picornavirus capsid-binding molecule with antiviral activity after the initial stage of viral uncoating. Antiviral Res. 21: 1535.
85. Rueckert, R. R., 1990. Picornaviridae and their replication, p. 507 548. In B. N. Fields, and D. M. Knipe (ed.), Virology. Raven Press Ltd., New York.
86. Samo, T. C.,, S. B. Greenberg,, R. B. Couch,, J. Quarles,, R. E. Johnson,, S. Hook,, and M. W. Harmon. 1983. Efficacy and tolerance of intranasal applied recombinant leukocyte A interferon in normal volunteers. J. Infect. Dis. 148: 535 542.
87. Sasaki, 0.,, T. Karaki,, and J. Imanishi. 1986. Protective effect of interferon on infections with hand, foot and mouth disease virus in newborn mice. J. Infect. Dis. 153: 498 502.
88. Saunders, K.,, and A. M. Q. King. 1982. Guanidine-resistant mutants of aphthovirus induce the synthesis of an altered nonstructural polypeptide, P34. J. Virol. 42: 389 394.
89. Schiff, G. M.,, J. R. Sherwood,, E. C. Young,, and L. J. Mason. 1992. Prophylactic efficacy of WIN 54954 in prevention of experimental human coxsackievirus A21 infection and illness. Antiviral Res. 17 ( Suppl. 1): 92.
90. See, D.,, and J. Tilles. 1993. WIN 54954 treatment of mice infected with a diabetogenic strain of group B coxsackievirus. Antimicrob. Agents Chemother. 37: 1593 1598.
91. See, D. M.,, and J. G. Tilles. 1992. Treatment of coxsackievirus A9 myocarditis in mice with WIN 54954. Antimicrob. Agents Chemother. 36: 425 428.
92. Sim, I. S.,, and R. L. Cerruti. 1987. Recombinant interferons alpha and gamma: comparative antiviral activity and synergistic interaction in encephalomyocarditis virus infection of mice. Antiviral Res. 8: 209 221.
93. 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: 1286 1293.
94. Smith, R. A.,, and E. H. Norris. 1987. Antiviral therapy. Adv. Exp. Med. Biol. 209: 297 304.
95. 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: 849 853.
96. Strikas, R. A.,, L. J. Anderson,, and R. A. Parker. 1986. Temporal and geographic patterns of isolates of nonpolio enterovirus in the United States, 1970-1983. J. Infect. Dis. 153: 346 351.
97. Taylor, H. R.,, J. C. Cadet,, and A. Sommer. 1982. Folk medicines and acute hemorrhagic conjunctivitis. Am. J. Ophthalmol. 94: 555 560.
98. 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. Nad. Acad. Sci. USA 86: 4907 4911.
99. Turner, R. B.,, F. J. Dutko,, N. H. Golstein,, G. Lockwood,, and F. G. Hay den. 1993. Efficacy of oral WIN 54954 for prophylaxis of experimental rhinovirus infection. Antimicrob. Agents Chemother. 37: 297 300.
100. Vallbracht, A.,, P. Gabriel,, J. Zahn,, and B. Fleming. 1985. Hepatitis A virus infection and the interferon system. J. Infect. Dis. 152: 211 213.
101. Vlaspolder, R.,, C. A. Kraaijeveld,, R. Van Buuren,, M. Harmsen,, B. J. Benaissa-Trouw,, and H. Snippe. 1988. Prophylaxis and therapy of virulent encephalomyocarditis virus in mice by monoclonal antibodies. Arch. Virol. 98: 123 130.
102. 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: 2069 2074.
103. Yasin, S. R.,, W. al-Nakib,, and D.A. Tyrrell. 1990. Pathogenesis for humans of human rhinovirus type 2 mutants resistant to or dependent on chalcone Ro 09-0410. Antimicrob. Agents Chemother. 34: 963 966.
104. Yin-Murphy, M. 1984. Acute hemorrhagic conjunctivitis. Prog. Med. Virol. 29: 43 44.
105. Zachoval, R.,, M. Kroener,, M. Brommer,, and F. Deinhardt. 1990. Serology and interferon production during the early phase of acute hepatitis A.J. Infect. Dis. 161: 353 354.
106. Zeichardt, H.,, M.J. Otto,, M. A. McKinlay,, P. Willingmann,, and K.-O. Habermehl. 1987. Inhibition of poliovirus uncoating by disoxaril (WIN 51711). Virology 160: 281 285.
107. Zhang, A.,, R. G. Nanni,, G. F. Arnold,, D. A. Oren,, T. Li,, A. Jacobo-Molina,, R. L. Williams,, G. Kamer,, D. A. Rubenstein,, Y. Li,, E. Rozhon,, S. Cox,, P. Buontempo,, J. O'Connell,, J. Schwartz,, G. Miller,, C. Nash,, B. Bauer,, R. Versace,, A. Ganguly,, V. Girijavallabhan,, and E. Arnold. 1991. Structure of a complex of human rhinovirus 14 with a water soluble antiviral compound SCH 38057. J. Mol. Biol. 230: 857 867.
108. Zhang, A.,, R. G. Nanni,, D. A. Oren,, E. J. Rozhon,, and E. Arnold. 1992. Three-dimensional structure—activity relationships for antiviral agents that interact with picornavirus capsids. Semin. Virol. 3: 453 471.


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Comparison of amino acids in the drug-binding pockets of different picornaviruses

Citation: O'Connell J, Albin R, Blum D, Grint P, Schwartz J. 1995. Development of Antiviral Agents for Picornavirus Infections, p 419-434. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch18
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Conformational changes induced in main chains of HVR14 by capsid-binding antiviral compounds

Citation: O'Connell J, Albin R, Blum D, Grint P, Schwartz J. 1995. Development of Antiviral Agents for Picornavirus Infections, p 419-434. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch18

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