1. dengue virus
WHO: million cases/yr

2. Acknowledgements Sharon Isern, PhD Yancey Hrobowski, PhD
Joshua Costin, PhD
Kelli Barr, PhD
Krystal Fontaine
Craig Rees
Cindo Nicholson
Robert Garry, PhD - Tulane University
Ram Samudrala, PhD - University of Washington
Tom Monath, PhD - Acambis
Michael Holbrook, PhD - UTX, Galveston
Elizabeth Hunsperger, PhD - CDC, San Juan
ONR /DTRA /US Army / NIH

4. Kaufmann, et al. PNAS 103:12400-12404 (2006)

5. Zhang, et al. Nature Structural Biology 10:907 (2003)

6. Development of novel virus entry inhibitors
host cell
inhibitor
entry blocked

7. HOW DO YOU DEVELOP A VIRAL INHIBITOR?

9. Dengue Plaque Assay control control peptide 57IIb
peptide 80FP peptide 81IIb peptide 59PA

12. DON’T GET FOOLED!

13. No Toxicity in MTT Assay

14. Effect of Scrambled Amino Acid Order

15. Effect of dengue inhibitory peptides on Sindbis virus infectivity

16. DENV-2 MAILGDTAWDFGSLGGVFTSIGKALHQVFGAIY
DENV I------V--LI--I--TA-
DENV V---LN-L--MV--I--SA-
DENV E V---L--L---V-----SV-
WNV L-A V V-----GAF
YFV L-VM--V----S-A--F------GI-T---SAF
SLEV L-V I------I GAF
JEV L-A I----N-I---V-----GAF
RSSEV LTVI-EH------T--FL T-L-GAF
CEEV LTVI-EH------A--FLS-I-----T-L-GAF

19. HOW DO THESE THINGS WORK?

23. Next Steps?