Strategies for antiviral drug discovery

Antiviral Chemistry and Chemotherapy

Volumn 9, Issue 4, 1998, Pages 283-302

  Jones, P S ^a  

^a ROCHE PRODUCTS LTD   (United Kingdom)

Author keywords

High throughput screening; Lead generation; Lead optimization; Parallel synthesis

Indexed keywords

ACICLOVIR; ANTISENSE OLIGONUCLEOTIDE; ANTIVIRUS AGENT; FIALURIDINE; FOMIVIRSEN; IDOXURIDINE; IMIQUIMOD; IMMUNOMODULATING AGENT; LAMIVUDINE; NUCLEOSIDE ANALOG; PROTEINASE INHIBITOR; RIBOZYME; RNA DIRECTED DNA POLYMERASE INHIBITOR; SIALIDASE INHIBITOR; TRANSACTIVATOR PROTEIN; VIDARABINE; VIRUS ENZYME; VIRUS PROTEIN; VIRUS VACCINE; ZANAMIVIR; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; DRUG DESIGN; DRUG SCREENING; HERPES SIMPLEX VIRUS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE RESPONSE; INFLUENZA VIRUS; NONHUMAN; PRIORITY JOURNAL; REVIEW; VIRUS INFECTION; X RAY CRYSTALLOGRAPHY;

ANTI-HIV AGENTS; ANTIVIRAL AGENTS; DRUG EVALUATION, PRECLINICAL; HIV PROTEASE INHIBITORS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NUCLEOSIDES; REVERSE TRANSCRIPTASE INHIBITORS;

EID: 0031849739     PISSN: 09563202     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (118)

1. Ahuja SK &. Murphy PM (1993) Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. Journal of Biological Chemistry 268:20691-20694.
2. Anonymous (1998) Current antiviral agents factfile 4th edition: part I - herpesviruses, hepatitis viruses and respiratory viruses. International Antiviral News 6:83-91.
3. Artusson PA & Borchardt RT (1997) Intestinal drug absorption and metabolism in cell cultures: caco-2 and beyond. Pharmaceutical Research 14:1655-1658.
4. Azad RF, Driver VB, Tanaka K, Crooke RM & Anderson KP (1993) Antiviral activity of a phosphorothioate oligonucleotide complementary to RNA of the human cytomegalovirus major immediate early region. Antimicrobial Agents and Chemotherapy 37:1945-1954.
5. Baba M, Tanaka H, De Clercq E, Pauwels R, Balzarini J, Schols D, Nakashima H, Perno C, Walker RT & Miyasaka T (1989) Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivative. Biochemical and Biophysical Research Communications 165:1375-1381.
6. Babe LM & Craik CS (1997) Viral proteases: evolution of diverse structural motifs to optimize function. Cell 91:427-430.
7. Bacher JM &. Ellington AD (1998)Nucleic acid selection as a tool for drug discovery. Drug Discovery Today 3:265-273.
8. Balzarini J, Karlsson A, Aquaro S, Perno C, Cahard D, Naesens L, De Clercq E & McGuigan C (1996) Mechanism of anti-HIV action of masked alanyl d4T-MP derivatives. Proceedings of the National Academy of Sciences, USA 93:7295-7299.
9. Bartenschlager R (1997) Molecular targets in inhibition of hepatitis C virus replication. Antiviral Chemistry & Chemotherapy 8:281-301.
10. Beauchamp LM, Orr GF, de Miranda P, Burnette T &, Krenitsky TA (1992) Amino acid ester prodrugs of acyclovir. Antiviral Chemistry & Chemotherapy 3:157-164.
11. Bergstrom T (1998) Relationship between herpesvirus and MS. Antiviral Research 37:A26.
12. Bethell RC & Smith PW (1997) Sialidase as a target for inhibitors of influenza virus replication. Expert Opinion on Investigational Drugs 6:1501-1509.
13. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL & Wood MJ (1995) Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrobial Agents and Chemotherapy 39:1546-1553.
14. Beutner KR, Tyring SK, Trofatter KF, Douglas JM, Spotswood S, Owens ML, Fox TL, Hougham AJ & Schmitt KA (1998) Imiquimod, a patient applied immune response modifier for the treatment of external genital warts. Antimicrobial Agents and Chemotherapy 42:789-794.
15. Bossart-Whittaker P, Carson M, Babu YS, Smith CD, Laver WG & Air GM (1993) Three dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydo-N-acetyl neuraminic acid. Journal of Molecular Biology 232:1069-1083.
16. Brandt CR, Spencer B, Imesch P, Garneau M & Deziel R (1996) Evaluation of a peptidomimetic ribonucleotide reductase inhibitor with a murine model of herpes simplex virus type 1 ocular disease. Antimicrobial Agents and Chemotherapy 40:1078-1084.
17. Bristol JA (editor) (1997) Annual Reports in Medicinal Chemistry, vol. 32, p. 372. San Diego: Academic Press.
18. Brownlee KA & Hamre DA (1951) Studies on chemotherapy of vaccinia virus 1. An experimental design for testing antiviral agents. Journal of Bacteriology 61:127-134.
19. Buchanan RA & Hess F (1985) Viderabine (Vira-A): pharmacology and clinical experience. In Viral Chemotherapy, vol. 2, pp. 109-143. Edited by D Hugar. Oxford: Pergamon Press.
20. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM & Moore PS (1994) Identification of herpes-like nDNA sequences in AIDS-associated Kaposi's sarcoma. Science 266:1865-1869.
21. Choi W, Wilson LJ, Yeola S & Liotta DC (1991) In situ complexation directs the stereochemistry of N-glycosylation in the synthesis of oxathiolanyl and dioxolanyl nucleoside analogues. Journal of the American Chemical Society 113:9377-9379.
22. Chong AKJ, Pegg MS & von Itztein M (1991) Characterisation of an ionisable group involved in binding and catalysis by sialidase from influenza virus. Biochemistry International 24:165-171.
23. Cianci C, Chung TDY, Meanwell N, Putz H, Hagen M, Colonno RJ & Krystal M (1996) Identification of N-hydroxamic acid and N-hydroxyimide compounds that inhibit the influenza virus polymerase. Antiviral Chemistry & Chemotherapy 7:353-360.
24. Colman PM, Varghese JN & Laver WG (1983) Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 303:41-44.
25. Davies WL, Grunert RR, Haff RF, McGahen JW, Neumayer EM, Paulshock M, Watts JC, Wood TR, Hermann EC & Hoffmann CE (1964) Antiviral activity of L-adamantanamine (Amantadine). Science 144:862-863.
26. De Lucca GV, Erickson-Viitanen S & Lam PYS (1997) Cyclic HIV protease inhibitors capable of displacing the active site structural water molecule. Drug Discovery Today 2:6-18.
27. Desjarlais RL, Seibel GL, Kuntz ID, Furth PS, Alvarez JC, Ortiz De Montellano PR, DeCamp DL, Babe LM & Craik CS (1990) Structure-based design of nonpeptide inhibitors specific for the human immunodeficiency virus 1 protease. Proceedings of the National Academy of Sciences, USA 87:6644-6648.
28. Diana GD & Pevear DC (1997) Antipicornavirus drugs: current status. Antiviral Chemistry & Chemotherapy 8:401-408.
29. Dienstag JL, Perrillo RP, Schiff ER, Bartholomew M, Vicary C & Rubin M (1995) A preliminary trial of lamivudine for chronic hepatitis B infection. New England Journal of Medicine 333:1657-1661.
30. Doong S, Tsai C, Schinazi RF, Liotta DC & Cheng Y (1991) Inhibition of the replication of hepatitis B virus in vitro by 2′,3′-dideoxy-3′-thiacytidine and related analogues. Proceedings of the National Academy of Sciences, USA 88:8495-8499.
31. Dyda F, Hickman AB, Jenkins TM, Engelman A, Craigie R & Davies DR (1994) Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases. Science 266:1981-1986.
32. Esnouf R, Ren J, Ross C, Jones Y, Stammers D & Stuart D (1995) Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors. Nature Structural Biology 2:303-308.
33. Frick LW, Adkison KK, Wells-Knecht KJ, Woollard P & Higton DM (1998) Cassette dosing: rapid in vivo assessment of pharmacokinetics. Pharmaceutical Sciences Technology Today 1:12-18.
34. Fried MW, Di Bisceglie AM, Strauss SE, Savarese B, Beames MP & Hoofnagle JH (1992) FIAU: a new oral anti-viral agent, profoundly inhibits HBV DNA in patients with chronic HBV. Hepatology 16:127A.
35. Furman PA, Wilson JE, Reardon JE & Painter GR (1995) The effect of absolute configuration on the anti-HIV and anti-HBV activity of nucleoside analogues. Antiviral Chemistry & Chemotherapy 6:345-355.
36. Gait MJ & Karn J (1995) Progress in anti-HIV structure-based drug design. Trends in Biotechnology 13:430-438.
37. Galasso GJ (1998) The International Society for Antiviral Research: The First Decade. Birmingham: ISAR Publications
38. Ghorpade A, Xia M, Hyman BT, Persidsky Y, Nukuna A, Bock P, Che M, Limoges J, Gendelman HE & Mackay CR (1998) Role of the beta-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia. Journal of Virology 72:3351-3361.
39. Hamy F, Felder ER, Heizmann G, Lazdins J, Aboul-Ela F, Varani G, Karn J & Klimkait T (1997) An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proceedings of the National Academy of Sciences, USA 94:3548-3553.
40. Harrison CJ, Jenski L, Voychehokski T & Bernstein DI (1988) Modification of immunological responses and clinical disease during topical R-837 treatment of genital HSV-2 infection. Antiviral Research 10:209-223.
41. Higuchi T & Stella V (1975) Pro-drugs as novel drug delivery systems. ACS Symposium Series, vol. 14. Washington, DC: ACS.
42. Hong L, Zhang X, Foundling S, Hartsuck JA & Tang J (1997) Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs. FEBS Letters 420:11-16.
43. Johnson RE, Hahmias AJ, Magder LS, Lee FK, Brooks CA & Snowden CB (1989) A seroepidemiologic survey of the prevalence of herpes simplex virus type 2 infections in the United States. New England Journal of Medicine 321:7-12.
44. Kaufman HE & Heidelberger C (1964) Therapeutic antiviral action of 5-trifluoromethyl-2′deoxyuridine in herpes simplex keratitis. Science 145:585-586.
45. Kempf DJ, Norbeck DW, Codacovi LM, Wang XC, Kohlbrenner WE, Wideburg NE, Paul DA, Knigge MF, Vasavanonda S, Craig-Kennard A, Saldivar A, Rosenbrook W, Clement JJ, Plattner JJ & Erickson E (1990) Structure-based C2 symmetric inhibitors of HIV protease. Journal of Medicinal Chemistry 33:2687-2689.
46. Kick EK & Ellman JA (1995) Expedient method for the solid-phase synthesis of aspartic acid protease inhibitors directed toward the generation of libraries. Journal of Medicinal Chemistry 38:1427-1430.
47. Kim CU, Lew W, Williams MA, Zhang L, Liu H, Swaminathan S, Bischofberger N, Chen MS, Tai CY, Mendel DB, Laver WG & Stevens RC (1997) Influenza neuraminidase inhibitors possessing a novel Hydrophobic interaction in the enzyme active site: design, synthesis and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. Journal of the American Chemical Society 119:681-690.
48. Kim EE, Baker CT, Dwyer MD, Murcko MA, Rao BG, Tung RD & Navia MA (1995) Crystal structure of HIV-1 protease in complex with VX-478, a potent and orally bioavailable inhibitor of the enzyme. Journal of the American Chemical Society 117:1181-1182.
49. Kim JL, Morgenstern KA, Lin C, Fox T, Dwyer MD, Landro JA, Chambers SP, Markland W & Lepre CA (1996) Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 87:343-355.
50. Kim JL, Morgenstern KA, Griffith JP, Dwyer MD, Thomson JA, Murcko MA, Lin C & Caron PR (1998) Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding. Structure 6:89-100.
51. Kinchington D, Balzarini J & Field HJ (1997) Current antiviral agents factfile, 3rd edition: part II - human immunodeficiency viruses. International Antiviral News 5:161-174.
52. Krawczyk SH & Bischofberger N (1997) Non-HIV antiviral agents. In Annual Reports in Medicinal Chemistry, vol. 32, pp. 141-150. Edited by JA Bristol. San Diego: Academic Press.
53. Kumar PKR, Machida K, Urvil PT, Kakiuchi N, Vishnuvardhan D, Shimotohno K & Taira K (1997) Isolation of RNA aptamers specific to the NS3 protein of hepatitis C virus from a pool of completely random RNA. Virology 237:270-282.
54. Langtry HD & Campoli-Richards DM (1989) Zidovudine - a review of its pharmacodynamic and pharmacokinetic properties and its therapeutic efficacy. Drugs 37:408-450.
55. Lavie A, Vetter IR, Konrad M, Goody RS, Reinstein J & Schlichting I (1997) Structure of thymidylate kinase reveals the cause behind the limiting step in AZT activation. Nature Structural Biology 4:601-604.
56. Levine AJ (1992a) Viruses, p. 74. New York: Scientific American Library.
57. Levine AJ (1992b) Viruses, pp. 165-166. New York: Scientific American Library.
58. Levine AJ (1992c) Viruses, pp. 56-65. New York: Scientific American Library.
59. Lewis EJ, Bishop J, Chadwick J, Cuthill S, Dunford P, Greenham AK, Gibson V, Kelly F, Mulqueen M, Roberts NA, Szymkowski D, Christensen N, Kreider JW, Kilkuskie R & Roberts P (1998) In vivo activity of an antisense oligonucleotide targeted against the El region of human papillomavirus. Antiviral Research 37:A47.
60. Li W, Escarpe PA, Eisenberg EJ, Cundy KC, Sweet C, Jakeman KJ, Merson J, Lew W, Williams M, Zhang L, Kim CU, Bischofberger N, Chen MS & Mendel DB (1998) Identification of GS4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS4071. Antimicrobial Agents and Chemotherapy 42:647-653.
61. Lipinski CA, Lombardo F, Dominy BW & Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advances in Drug Delivery Reviews 23:3-25.
62. Liuzzi M, Deziel R, Moss N, Beaulieu P, Bonneau A, Bousquet C, Chafouleas JG, Garneau M, Jaramillo J, Krogsrud RL, Lagace L, McCollum RS, Nawoot S & Guindon Y (1994) A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo. Nature 372:695-698.
63. Liuzzi M, Crute JJ, Grygon CA, Hargrave KD, Simoneau B, Faucher A, Bolger G, Duan J, Kibler P & Cordingley MG (1998) Aminothiazolyl-phenyl-based inhibitors of HSV helicase-primase: a novel class of orally active antiherpetic agents. Antiviral Research 37:A42.
64. Llinas-Brunet M, Moss N, Scouten E, Liuzzi M & Deziel R (1996) Peptidomimetic inhibitors of herpes virus ribonucleotide reductase. Correlation between herpes simplex and varicella zoster virus. Biorganic and Medicinal Chemistry Letters 6:2881-2886.
65. Love RA, Parge HE, Wickersham JA, Hostomsky Z, Habuka N, Moomaw EW, Adachi T & Hostomska Z (1996) The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell 87:331-342.
66. Lutzke RAP, Eppens NA, Weber PA, Houghten RA & Plasterk RHA (1995) Identification of a hexapeptide inhibitor of the human immunodificiency virus integrase protein by using a combinatorial chemical library. Proceedings of the National Academy of Sciences, USA 92:11456-11460.
67. McGuigan C, Cahard D, Sheeka HM, De Clercq E & Balzarini J (1996) Aryl phosphoramidate derivatives of d4T have improved anti-HIV efficacy in tissue culture and may act by the generation of a novel intracellular metabolite. Journal of Medicinal Chemistry 39:1748-1753.
68. McKenzie R, Fried MW, Sallie R, Conjeevaram H, Di Bisceglie AM, Park Y, Savarese B, Kleiner D, Tsokos M, Luciano C, Pruett T, Stotka J, Straus SE & Hoofnagle JH (1995) Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic HBV. New England Journal of Medicine 333:1099-1105.
69. Martin JA, Redshaw S & Thomas GJ (1995) Inhibitors of HIV proteinase. In Progress in Medicinal Chemistry, vol. 32, pp. 239-287. Edited by GP Ellis & DK Luscombe. Oxford: Elsevier.
70. Matthews DA, Smith WW, Ferre RA, Condon B, Budahazi G, McElroy HE, Gribskov CL & Worland S (1994) Structure of human rhinovirus 3C protease reveals a trypsin-like polypeptide fold, RNA-binding site, and means for cleaving precursor polyprotein. Cell 77:761-771.
71. Meindl P, Bodo G, Palese P, Schulman J & Tuppy H (1974) Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydo-N-acetylneuraminic acid. Virology 58:457-463.
72. Merluzzi M, Hargrave KD, Labadia M, Grozinger K, Skoog M, Wu JC, Shih C, Eckner K, Hattox S, Adams J, Rosenthal AS, Faanes R, Eckner RJ, Koup RA & Sullivan JL (1990) Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science 250:1411-1413.
73. Miller M, Schneider J, Sathyanarayana BK, Toth MV, Marshall GR, Clawson L, Selk L, Kent SBH & Wlodawer A (1989) Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 angstom resolution. Science 246:1149-1152.
74. Molla A & Kohlbrenner WE (1997) Resistance to antiretroviral drug therapy. Annual Reports in Medicinal Chemistry 32:131-140.
75. Moss N, Beaulieu P, Duceppe J, Ferland J, Gauthier J, Ghiro E, Goulet S, Grenier L & Llinas-Brunet M (1995) Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase: a new class of antiviral agents. Journal of Medicinal Chemistry 38:3617-3623.
76. Moss N, Beaulieu P, Duceppe J, Ferland J, Gauthier J, Ghiro E, Goulet S, Guse I & Llinas-Brunet M (1996a) Ureido-based peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase: an investigation of inhibitor bioactive conformation. Journal of Medicinal Chemistry 39:2178-2187.
77. Moss N, Beaulieu P, Duceppe J, Ferland J, Garneau J, Gauthier J, Ghiro E, Goulet S, Guse I, Jarmillo J, Llinas-Brunet M, Malenfant E, Plante R, Poirier M, Soucy F, Wernic D, Yoakim C & Deziel R (1996b) Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase with improved in vivo antiviral activity. Journal of Medicinal Chemistry 39:4173-4180.
78. Pallella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ & Holmberg SD (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. New England Journal of Medicine 338:853-860.
79. Patel DV & Gordon EM (1996) Applications of small-molecule combinatorial chemistry to drug discovery. Drug Discovery Today 1:134-144.
80. Pauling L (1946) Molecular architecture and biological reactions. Chemical and Engineering News 24:1375-1377.
81. Pauwels R, Andries K, Desmeyter J, Schols D, Kukla MJ, Breslin HJ, Raeymaeckers A, Van Gelder J, Woestenborghs R, Heykants J, Schellekens K, Janssen MAC, De Clercq E & Janssen PAJ (1990) Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature 343:470-474.
82. Pearl LH & Taylor WR (1987) A structural model for the retroviral proteases. Nature 329:351-354.
83. Ping C, Almassy R, Tsuge H, Matthews D, Pinko C, Gribskov C & Kan C (1996) Structure of the human cytomegalovirus protease catalytic domain reveals a novel serine protease fold and catalytic triad. Cell 86:835-843.
84. Prasad JVNV, Para KS, Lunney EA, Ortwine DF, Dunbar JB, Ferguson D, Tummino PJ, Hupe D, Tait BD, Domagala JM, Humblet C, Bhat TN, Liu B, Guerin DMA, Baldwin ET, Erickson JW & Sawyer TK (1994) Novel series of achiral, low molecular weight and potent HIV-1 protease inhibitors. Journal of the American Chemical Society 116:6989-6990.
85. Prasad JVNV, Para KS, Tummino PJ, Ferguson D, McQuade TJ, Lunney EA, Rapundalo ST, Batley BL, Hinhorani G, Domagala JM, Gracheck SJ, Bhat TN, Liu B, Erickson JW & Sawyer TK (1995) Nonpeptidic potent HIV-1 protease inhibitors: (4-hydroxy-6-phenyl-2-oxo-2H-pyran-3-yl)thiomethanes that span P1-P2′ subsites in a unique mode of active site binding. Journal of Medicinal Chemistry 38:898-905.
86. Qiu X, Culp JS, DiLella AG, Hellmig B, Hoog SS, Janson CA, Smith WW & Abdel-Meguid SS (1996) Unique fold and active site in cytomegalovirus protease. Nature 383:275-279.
87. Qiu X, Janson C, Culp JS, Richardson SB, Debouck C, Smith WW & Abdel-Meguid SS (1997) Crystal structure of varicella-zoster virus protease. Proceedings of the National Academy of Sciences, USA 94:2874-2879.
88. Reich SH, Melnick M, Davies JF, Appelt K, Lewis KK, Fuhry MA, Pino M, Trippe AJ, Nguyen D, Dawson H, Wu B, Musick L, Kosa M, Kahil D, Webber S, Gehlhaar DK, Andrada D & Shetty B (1995) Protein structure-based design of potent orally bioavailable nonpeptide inhibitors of human immunodeficiency virus protease. Proceedings of the National Academy of Sciences, USA 92:3298-3302.
89. Reiter M, Testerman TL, Miller RL, Weeks CE & Tomai MA (1994) Cytokine induction in mice by the immunomodulator imiquimod. Journal of Leukocyte Biology 55:234-240.
90. Ren J, Esnouf R, Garman E, Somers D, Ross C, Kirby I, Keeling J, Darby G, Jones Y, Stuart D & Stammers D (1995) High resolution structures of HIV-1 RT from four RT inhibitor complexes. Nature Structural Biology 2:293-302.
91. Roberts NA, Martin JA, Kinchington D, Broadhurst AV, Craig JC, Duncan IB, Galpin SA, Handa BK, Kay J, Krohn A, Lambert RW, Merrett JH, Mills JS, Parkes KEB, Redshaw S, Ritchie AJ, Taylor DL, Thomas GJ & Machin PJ (1990) Rational design of peptide-based HIV proteinase inhibitors. Science 248:358-361.
92. Roberts NA, Craig JC & Sheldon J (1998) AIDS resistance and cross-resistance with saquinavir and other HIV protease inhibitors: theory and practice. AIDS 12:453-460.
93. Romero DL, Busso M, Tan C, Reusser F, Palmer JR, Poppe SM, Aristoff PA, Downey KM, So AG, Resnick L & Tarpley WG (1991) Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication. Proceedings of the National Academy of Sciences, USA 88:8806-8810.
94. Schabel FM (1968) The antiviral activity of 9-beta-arabino-furanosyladenine (ara-A). Chemotherapy 13:321-338.
95. Schramm HJ, Nakashima H, Schramm W, Wakayama H & Yamamoto N (1991) HIV-1 reproduction is inhibited by peptides derived from the amino termini and carboxyl-termini of HIV-1 protease. Biochemical and Biophysical Research Communications 179:847-851.
96. Shieh H, Kurumbail RG, Stevens AM, Stegeman RA, Sturman EJ, Pak JY, Wittwer AJ, Palmier MO, Wiegand RC, Holwerda BC & Stallings WC (1996) Three dimensional structure of human cytomegalovirus protease. Nature 383:279-282.
97. Shigeta S (1998) Approaches to antiviral chemotherapy for acute respiratory infections. Antiviral Chemistry & Chemotherapy 9:93-107.
98. Sneader W (1985a) Drug Discovery: The Evolution of Modern Medicines, p. 292. Chichester: John Wiley.
99. Sneader W (1985b) Drug Discovery: The Evolution of Modern Medicines, p. 351. Chichester: John Wiley.
100. Spector FC, Liang L, Giordano H, Sivaraja M & Peterson MG (1998) T157602, a 2-amino-thiazole inhibits HSV replication by interacting with the UL5 component of the UL5/8/52 helicase primase complex. Antiviral Research 37:A43.
101. Sullenger BA (1995) Revising messages travelling along the cellular information superhighway. Chemistry and Biology 2:249-253.
102. Szymkowski DE (1996) Developing antisense oligonucleotides from the laboratory to clinical trials. Drug Discovery Today 1:415-428.
103. Thaisrivongs S, Tomich PK, Watenpaugh KD, Chong K, Howe WJ, Yang C, Strohbach JW, Turner SR, McGrath JP, Bohanon MJ, Lynn JC, Mulichak AM, Spinelli PA, Hinshaw RR, Pagano PJ, Moon JB, Ruwart MJ, Wilkinson KF, Rush BD, Zipp GL, Dalga RJ, Schwende FJ, Howard GM, Padbury GE, Toth LN, Zhao Z, Koeplinger KA, KakukTJ, Cole SL, Zaya RM, Piper RC & Jeffrey P (1994) Structure-based design of HIV protease inhibitors: 4-hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors. Journal of Medicinal Chemistry 37:3200-3204.
104. Tomassini J, Selnick H, Davies ME, Armstrong ME, Baldwin J, Bourgeois M, Hastings J, Hazuda D & Lewis J (1994) Inhibition of cap(m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds. Antimicrobial Agents and Chemotherapy 38:2827-2837.
105. Tomassini JE, Davies ME, Hastings JC, Lingham R, Mojena M, Raghoobar SL, Singh SB, Tkacz JS & Goetz MA (1996) A novel antiviral agent which inhibits the endonuclease of influenza viruses. Antimicrobial Agents and Chemotherapy 40:1189-1193.
106. Tong L, Qian C, Massariol M, Bonneau PR, Cordingley MG & Lagace L (1996) A new serine-protease fold revealed by the crystal structure of human cytomegalovirus protease. Nature 383:272-275.
107. Underwood MR, Harvey RJ, Stanat SC, Hemphill Ml, Miller T, Drach JC, Townsend LB & Biron KK (1998) Inhibition of human cytomegalovirus DNA maturation by a benzimidazole ribonucleoside is mediated through the UL89 gene product. Journal of Virology 72:717-725.
108. Urvil PT, Kakiuchi N, Nobuko, Zhou D & Shimotohno K (1997) Selection of RNA aptamers that bind specifically to the NS3 protease of hepatitis C virus. European Journal of Biochemistry 248:130-138.
109. Vere Hodge RA, Sutton D, Boyd MR, Harnden MR & Jarvest RL (1989) Selection of the oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydrox-ymethylbut-1-yl)guanine; penciclovir]. Antimicrobial Agents and Chemotherapy 33:1765-1773.
110. von Itztein M, Wu W, Kok GB, Pegg MS, Dyason, JC, Jin B, Phan TV, Smythe ML, White HF, Oliver SW, Colma PM, Varghese JN, Ryan DM, Woods JM, Bethell RC, Hotham VJ, Cameron JM & Penn CR (1993) Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 363:418-423.
111. Wade RC (1997) 'Flu' and structure-based drug design. Structure 5:1139-1145.
112. Wagner G (1995) The importance of being floppy. Nature Structural Biology 2:255-257.
113. White PW (1998) Understanding the molecular mechanism of viral resistance to peptidomimetic inhibitors of ribonucleotide reductase. Biochimica et Biophysica Acta 1382:102-110.
114. Wilson IA, Skehel JJ & Wiley DC (1981) Structure of the haemogglutinin membrane glycoprotein of influenzavirus at 3 Angstrom resolution. Nature 289:366-373.
115. Wintermeyer SM & Nahata MC (1995) Rimantadine: a clinical perspective. Annals of Pharmacotberapy 29:299-310.
116. Wlodawer A & Erickson JW (1993) Structure-based inhibitors of HIV-1 protease. Annual Reviews in Biochemistry 62:543-585.
117. Wlodawer A, Miller M, Jaskolski M, Sathyanarayana BK, Baldwin E, Weber IT, Selk LM, Clawson L, Schneider J & Kent BH (1989) Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science 245:616-621.
118. Yao N, Hesson T, Cable M, Hong Z, Kwong AD, Le HV & Weber PC (1997) Structure of the hepatitis C virus RNA helicase domain. Nature Structure Biology 4:463-467.