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WEST NILE VIRUS: NEW TARGETS FOR POTENTIAL ANTIVIRALS
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37. Song, G. Y.; Paul, V.; Choo, H.; Morrey, J.; Sidwell, R. W.; et al. Enantiomeric synthesis of D- and L- cyclopentyl nucleosides and their antiviral activity against HIV and West Nile virus. J. Med. Chem. 2001, 44, 3985 3993. 38. De Clercq, E.; Cools, M. Antiviral potency of adenosine analogs: correlation with inhibition of S-adenosylhomocysteine hydrolase. Biochem. Biophys. Res. Commun. 1985, 129, 306 311. 39. De Clercq, E. Antiviral agents: characteristic activity spectrum depending on the molecular target with which they interact. Adv. Virus Res. 1993, 42, 1 55. 40. Lo, M. K.; Tilgner, M.; Shi, P. Y. Potential high-throughput assay for screening of inhibitors of West Nile virus replication. J. Virol. 2003, 77, 12901 12906. 41. Perelygin, A. A.; Scherbik, S. V.; Zhulin, I. B.; Stockman, B. M.; Li, Y.; et al. Positional cloning of the murine avivirus resistance gene. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 9322 9327. 42. Murthy, H. M.; Clum, S.; Padmanabhan, R. Dengue virus NS3 serine protease. Crystal structure and insights into interaction of the active site with substrates by molecular modelling and structural analysis of mutational effects. J. Biol. Chem. 1999, 274, 5573 5580. 43. Leyssen, P.; de Clercq, E.; Neysts, J. Perspectives for the treatment of infections with Flaviviridae. Clin. Microbiol. Rev. 2000, 13, 67 82.
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The Emergence of Pandemic In uenza A: Bioterrorist Versus Mother Nature
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Retroscreen Virology Ltd., Centre for Infectious Diseases, Bart s and The London Queen Mary s School of Medicine and Dentistry
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In uenza A quite rightly can be viewed as the most threatening virus on our planet. It looks toward us, its human victims, with a two-sided face the epidemic face and the pandemic face. It could be assumed that the pandemic side of the face is the more important side to avoid, but this is wrong. We must not gaze on either face. When in uenza emerges in pandemic mode, probably (but not with certainty) from an avian, pig, or horse ecosystem, it nds a virgin population in our human world, now exceeding six billion. What other virus could spread around the globe and kill 40 million citizens of the world in 18 months But this was not the end of the effects of the Great Spanish 1918 in uenza pandemic: the virus revisited more or less yearly until it was suddenly displaced by another virus, Asian in uenza A in 1957 (Table 13.1). A quick totaling of yearly epidemic deaths from 1918 to 1957 gives an astonishing gure of mortality that even exceeds the hammer blow of the dark months at the end of the Great War.1 When the in uenza A virus rst emerged from a presumed avian reservoir at the end of the ice age 10,000 or so years ago, there was a distinct dif culty of nding new human victims. For example, at that time only a few hundred settlers were in the London region near our hospital in a community now containing four million people. At that time a traveler would have to walk 100 miles to nd another small settlement perhaps near Salisbury. But today we have a truly global community of six billion people linked so that two million people are moving each day by plane while perhaps 100 million are journeying in their homelands. In uenza, like all viruses, is opportunistic. In 1918 it had the unprecedented opportunity to spread at
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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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THE EMERGENCE OF PANDEMIC INFLUENZA A
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TABLE 13.1 Global Impact of Pandemic or Potential Pandemics of In uenza in the Nineteenth, Twentieth, and Twenty- rst Centuries
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Year Colloquial Name and Subtype Source Emerged in eastern Russia and spread westward Impact Less than 1918 pandemic; possibly mortality similar to the 1957 H2N2 virus Pandemic with 40 million deaths globally.
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