Antiviral Drug Discovery for Emerging Diseases and Bioterrorism Threats PDF
Preview Antiviral Drug Discovery for Emerging Diseases and Bioterrorism Threats
ANTIVIRAL DRUG DISCOVERY FOR EMERGING DISEASES AND BIOTERRORISM THREATS ANTIVIRAL DRUG DISCOVERY FOR EMERGING DISEASES AND BIOTERRORISM THREATS Edited by Paul F. Torrence Northern Arizona University A JOHN WILEY & SONS, INC., PUBLICATION Copyright#2005byJohnWiley&Sons,Inc.Allrightsreserved. PublishedbyJohnWiley&Sons,Inc.,Hoboken,NewJersey. PublishedsimultaneouslyinCanada. 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Wileyalsopublishesitsbooksinavarietyofelectronicformats.Somecontentthatappearsinprint, however,maynotbeavailableinelectronicformat.FormoreinformationaboutWileyproducts,visitour websiteatwww.wiley.com LibraryofCongressCataloging-in-PublicationData: Antiviraldrugdiscoveryforemergingdiseasesandbioterrorismthreats/editedbyPaulF.Torrence. p. ; cm. Includesbibliographicalreferencesandindex. ISBN-13978-0-471-66827-5(cloth:alk.paper) ISBN-100-471-66827-3(cloth:alk.paper) 1.AntiviralAgents. 2.Drugdevelopment 3.Bioterrorism. [DNLM: 1.AntiviralAgents–therapeuticuse. 2.Bioterrorism–prevention&control. 3.CommunicableDiseases,Emerging–drugtherapy. 4.CommunicableDiseases,Emerging– prevention&control. 5.DrugDesign.QV268.5A62952005]I.Torrence,PaulF.II.Title. RM411.A57472005 616.901061–dc22 2004019934 PrintedintheUnitedStatesofAmerica 10987654321 CONTENTS Preface vii Contributors ix 1. Introduction: Pestilence, Plague, Bioterrorism 3 PaulF.Torrence 2. Viral Bioterrorism and Antiviral Countermeasures 17 MikeBray 3. Overview of Antiviral Drug Discovery and Development 31 ChristopherK.Tseng 4. Antiviral Drug Targets and Strategies for Emerging Viral Diseases and Bioterrorism Threats 83 ErikDeClercq 5. Perspectives for the Therapy Against Arenavirus Infections 115 ElsaB.DamonteandCybeleC. Garc´ıa 6. S-Adenosylhomocysteine Hydrolase Inhibitors as a Source of Anti-Filovirus Agents 139 StewartW.SchnellerandMinminYang 7. Antiviral Strategies for Ebola Virus 153 JillianM.Licata andRonaldN.Harty 8. IMPDH Inhibitors: Discovery of Antiviral Agents Against Emerging Diseases 179 Vasu Nair 9. Lethal Mutagenesis: Exploiting Error-Prone Replication of Riboviruses for Antiviral Therapy 203 JasonD.GraciandCraigE.Cameron v vi CONTENTS 10. Structural Biology of Flaviviral Replication and Opportunities for Drug Design 223 KrishnaMurthy 11. Confronting New and Old Antiviral Threats: Broad Spectrum Potential of Prenylation Inhibitors 249 MenasheElazarandJeffreyS.Glenn 12. West Nile Virus: New Targets for Potential Antivirals 263 MatthiasKalitzky,HolgerRohde,andPeter Borowski 13. The Emergence of Pandemic Influenza A: Bioterrorist Versus Mother Nature 281 JohnS.Oxford,Alison Boyers,AlexMann,andR.Lambkin 14. Discovery and Development of New Antivirals for Smallpox 331 EarlR.Kern 15. Viral Countermeasures to the Host Interferon Response: Role of the Vaccinia Virus E3L and K3L Genes 353 JeffreyO.Langland,VanessaLancaster,and BertramL.Jacobs 16. Broad-Spectrum Antiviral Prophylaxis: Inhibition of Viral Infection by Polymer Grafting with Methoxypoly(ethylene glycol) 379 LoriL.McCoyandMarkD.Scott 17. Viral Evasion of the Interferon System: Novel Targets for Drug Discovery 397 PaulF.TorrenceandLindaPowell Index 417 PREFACE When I was just beginning my career at the National Institutes of Health as an organicchemistwhowished tocontributetomedicine in someway, Iwas advised to stay away from research on the discovery of antiviral agents sinceviruses were well under control. That was when the World Health Organization nearly had eliminated variola virus, the causative agent of smallpox and the worst killer in human history. Years earlier, Salk, Sabin, and Koprowski had given the world the meanstoeliminatepolio.Theseweremassiveaccomplishmentsandoptimismwas only natural. Of course, the antiviral naysayers could not read the future. And the future contained HIV/AIDS...and Ebola hemorrhagic fever...and West Nile virus. Respiratory syncytial virus, a significant cause of morbidity and mortality among infants and children, expanded its host range to the elderly and the immunosup- pressed. Epidemics of herpes and viral hepatitis became commonplace. Cytome- galovirus also took advantage of the biological niche provided by the unfortunate immunosuppressed. Yellow fever continued to attack, along with a host of other diseases,theaspirationsandwell-beingofmillionsuponmillionsinthedeveloping world, while simultaneously undermining economies and providing conditions for unrest and extremism. Virus names such as Nipah, Hendra, and the SARS virus became part of the common lexicon. And all the while, waiting like a card up a gamblersshirtsleeve,theinfluenzavirus,wildorbioengineered,remainstheaceof spades. The human toll of the 1918–1919 ‘‘Spanish’’ flu will never be known accurately, but best estimates are 20–40 million dead. We have changed the world dramatically in the past few decades. Indeed the humanalterationsbeganinearnestwiththeintroductionofagriculture,whichbred a series of formidable viruses, including variola (smallpox) and influenza. Yet the changeswroughtbyhumansoverthepast10,000yearsmaybedwarfedbywhatwe have ‘‘accomplished’’ in the past century or so. We have brought about massive habitat changes,penetrated ecological nicheswithaspeedandthoroughnessnever known in human history, destroyed ecosystems, contributedsubstantially toglobal warming,bredresistancetoourbestantibiotics,undergoneuncontainedpopulation expansion,andintroducedsomuchmobilitythatatanytimeagreatfractionofour number is crossing even the oceans that once provided a barrier to species migration. If all this were not enough to provide diseases, including those of viral origin, withastrongifnotinvinceablehand,considerthatmanyofthevirusesthatthreaten Homo sapiens are RNA viruses that exist as quasi-species or ‘‘swarms,’’ always vii viii PREFACE readytoexploitanewniche,alwayspreparedtomeetthechallengeofdrugtherapy with resistance. And then finally the coup de grace. As unfathomable as it may seem,therearetheextremistsandzealotswhothreatentouseanysuchagentsthey can obtain or engineer to carry out their agendas. As enemies of all decent people onearth,theirhatredmaybedirectedatthemorehighlydevelopednations,butthe result of their bioterrorism may set the struggling people of developing countries back a thousand years. Imagine reintroduction of smallpox to a continent already fighting the burden of HIV/AIDS, yellow fever, dengue, Ebola, malaria, river blindness, and on and on. In spite of the counsel I received to let antivirals alone, I fulfilled my contrary nature.Thathasledmetoknowandrespectanumberoffellowtravelersandsome of them are, I am pleased to say, contributors to this volume. This volume is intendedtoprovidereasonsforoptimisminviewofthedarkandpessimisticpicture I just painted above. The journal Emerging Infections Diseases kindly cooperated on the use of certain of their covers throughout the book, and the editior and authors are deeply grateful for this. Several individuals have been very helpful in the compilation of this effort. Bonnie Johnson provided excellent editorial assistance. Polyxeni Potter of Emer- ging Infectious Diseases provided assistance in garnering permission to reproduce covers from the journal. Amy Romano, Assistant Editor at John Wiley & Sons, providedvaluableadviceandpatience.RosalynFarkas,alsoatJohnWiley,helped pull it all together. PAUL F. TORRENCE Northern Arizona University Flagstaff, Arizona CONTRIBUTORS Peter Borowski, University Hospital Hamburg-Eppendorf, Institute for Infectious Diseases, 20246 Hamburg, Germany AlisonBoyers,RetroscreenVirology,Ltd.,CentreforInfectiousDiseases,Bart’sandThe LondonQueenMary’sSchoolofMedicineandDentistry,LondonE14NSUK Mike Bray, Biodefense Clinical Research Branch, OCR/OD/NIAID, National Institutes of Health, Bethesda, MD 20892 USA Craig E. Cameron, Department of Biochemistry and Molecular Biology, Penn- sylvania State University, University Park, PA 16802 USA ElsaB.Damonte, LaboratoriodeVirolog´ıa,DepartamentodeQu´ımicaBiolo´gica, FacultaddeCienciasExactasyNaturales,UniversidaddeBuenosAires,Ciudad Universitaria, 1428 Buenos Aires, Argentina Erik De Clercq, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium Menashe Elazar, Division of Gastroenterology and Hepatology, Stanford Uni- versity School of Medicine, Palo Alto, CA 94305 USA CybeleC.Garc´ıa, LaboratoriodeVirolog´ıa,DepartamentodeQu´ımicaBiolo´gica, FacultaddeCienciasExactasyNaturales,UniversidaddeBuenosAires,Ciudad Universitaria, 1428 Buenos Aires, Argentina Jeffrey S. Glenn, Division of Gastroenterology and Hepatology, Stanford Uni- versity School of Medicine, and Veterans Administration Medical Center, Palo Alto, CA 94305 USA Jason D. Graci, Department of Biochemistry and Molecular Biology, Pennsylva- nia State University, University Park, PA 16802 USA Ronald N. Harty, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA Bertram L. Jacobs, School of Life Sciences/Biodesign Institute, Arizona State University, Tempe, AZ 85287 USA Matthias Kalitzky, University Hospital Hamburg-Eppendorf, Institute for Infec- tious Diseases, 20246 Hamburg, Germany ix x CONTRIBUTORS Earl R. Kern, Department of Pediatrics, Division of Infectious Diseases, The University of Alabama at Birmingham, Birmingham, AL 35233 USA R.Lambkin, RetroscreenVirologyLtd.,CentreforInfectiousDiseases,Bart’sand The London Queen Mary’s School of Medicine and Dentistry, London E1 4NS UK Vanessa Lancaster, School of Life Sciences/Biodesign Institute, Arizona State University, Tempe, AZ 85287 USA Jeffrey O. Langland, School of Life Sciences/Biodesign Institute, Arizona State University, Tempe, AZ 85287 USA Jillian M. Licata, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA Lori L. McCoy, Canadian Blood Services and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5 Canada AlexMann,RetroscreenVirology,Ltd.,CentreforInfectiousDiseases,Bart’sand TheLondonQueenMary’sSchoolofMedicineandDentistry,LondonE14NSUK KrishnaMurthy, CenterforBiophysicalSciencesandEngineering,Universityof Alabama at Birmingham, Birmingham, AL 35294 USA Vasu Nair, Department of Pharmaceutical and Biomedical Sciences and The CenterforDrugDiscovery,TheUniversityofGeorgia,Athens,GA30606USA JohnS.Oxford, RetroscreenVirologyLtd.,CentreforInfectiousDiseases,Bart’sand TheLondonQueenMary’sSchoolofMedicineandDentistry,LondonE14NSUK Linda Powell, Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ 86011 USA Holger Rohde, University Hospital Hamburg-Eppendorf, Institute for Infectious Diseases, 20246 Hamburg, Germany Stewart W. Schneller, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849 USA Mark D. Scott, Canadian Blood Services and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5 Canada Paul F. Torrence, Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ 86011 USA Christopher K. Tseng, Antiviral Research and Antimicrobial Chemistry, DMID/ NIAID, National Institutes of Health, Bethesda, MD 20892 USA Minmin Yang, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849 USA
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