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53. Chang, I. Fear of SARS, fear of strangers. New York Times, May 21, 2003, Section A, Column 2, p. 31. 54. Person, B.; Sy, F.; Holton, K.; Govert, B.; Liang, A. National Center for Infectious Diseases/SARS Community Outreach Team. Fear and stigma: the epidemic within the SARS outbreak. Emerging Infect. Dis. 2004, 10, 358 363. 55. Levine, S. Sick cruise ships. Cleaning vessels. U.S. News World Rep. Dec 16, 2002, 133, 50. 56. Gunn, R. A.; Terranova, W. A.; Greenberg, H. B.; Yashuk, J.; Gary, G. W.; Wells, J. G.; Taylor, P. R.; Feldman, R. A. Norwalk virus gastroenteritis aboard a cruise ship: an outbreak on ve consecutive cruises. Am. J. Epidemiol. 1980, 112, 820 827. 57. McKinlay, M. A.; Pevear, D. C. Treatment of the picornavirus common cold by inhibitors of viral uncoating and attachment. Annu. Rev. Microbiol. 1992, 46, 635 654. 58. Flint, S. J.; Enquist, L. W.; Krug, R. M.; Racaniello, V. R.; Skalka, A. M. Prevention and control of viral diseases. In Principles of Virology: Molecular Biology, Pathogenesis, and Control, ASM Publishing, New York, 2000, pp. 662 712. 59. Kandel, R.; Hartshorn, K. L. Prophylaxis and treatment of in uenza virus infection. BioDrugs 2001, 15, 303 323. 60. Osondu-Alilonu, N.; Gross, P. A. In uenza: the recurring, re-emerging infection. Curr. Treatment Options Infect. Dis. 2003, 5, 129 136. 61. Hirt, M.; Nobel, S.; Ernesto, B. Zinc nasal gel for the treatment of common cold symptoms: a double blind, placebo-controlled trial. ENT J. 2000, 79, 778 782. 62. Mossad, S. B. Effect of zincum gluconicum nasal gel on the duration and symptom severity of the common cold in otherwise health adults. QJM 2003, 96, 35 43. 63. Novick, S. G.; Godfrey, J. C.; Godfrey, N. J.; Wilder, H. R. How does zinc modify the common cold Clinical observations and implications regarding mechanisms of action. Med. Hypotheses 1996, 46, 295 302. 64. Eby, G. A.; Davis, D. R.; Halcomb, W. W. Reduction in duration of common colds by zinc gluconate lozenges in a double blind study. Antimicrob. Agents Chemother. 1984, 25, 20 24. 65. Godfrey, J. C.; Conant-Sloane B.; Smith, D. S.; Turco, J. H.; Mercer, N.; Godfrey, N. J. Zinc gluconate and the common cold: a controlled study. J. Int. Med. Res. 1992, 20, 234 246. 66. Korant, B. D.; Butterworth, B. E. Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides. J. Virol. 1976, 18, 298 306.
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Viral Evasion of the Interferon System: Novel Targets for Drug Discovery
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Department of Chemistry and Biochemistry, Northern Arizona University
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The paradigms of antiviral drug discovery have resulted in the pursuit of the classical targets of virus replication known to all students of virology; namely, attachment, penetration, uncoating, replication, maturation, and release. Yet, the ongoing battles of evolution have produced a host of other potential antiviral drug targets that to date have not been exploited to alter the course of virus-induced disease. Viruses and their hosts have coevolved and therefore have developed the means to contain and/or to evade one another. Vertebrate hosts have complex immune systems. In order for a virus to survive, it must replicate amidst the onslaught of the host immune defenses. Interferons (IFNs) play a key role in establishing this armament that triggers the activation of interferon-stimulated genes and elicits an antiviral state to curb viral infections. In response, viruses have evolved mechanisms to circumvent the interferon-induced defenses. Nearly fty years ago, Isaacs and Lindenmann identi ed and described the antiviral and cytostatic properties of interferons.1 These pathways are increasingly more complex. The dynamic process of viral evasion of the host IFN system can be attributed to the many years of coevolution and adaptation of viruses to produce proteins that downregulate IFN production, or block the actions of the products of this pathway. This is a rapidly expanding research arena and yields an array of potential targets for therapeutic intervention with viral infections. We do not pretend to review this eld exhaustively, but simply point out here some ndings of relevance to the domain of emerging diseases and biodefense concerns.
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Antiviral Drug Discovery for Emerging Diseases and Bioterrorism Threats. Edited by Paul F. Torrence Copyright # 2005 John Wiley & Sons, Inc.
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