dengue virus

1
dengue virus
WHO 50 - 100 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

3
(No Transcript)
4
Kaufmann, et al. PNAS 10312400-12404 (2006)
5
Zhang, et al. Nature Structural Biology 10907
(2003)
6
Development of novel virus entry inhibitors
virus
host cell
inhibitor
entry blocked
7

• HOW DO YOU DEVELOP A VIRAL INHIBITOR?

8
(No Transcript)
9
Dengue Plaque Assay
control control
peptide 57IIb
peptide 80FP peptide 81IIb
peptide 59PA
10
(No Transcript)
11
(No Transcript)
12

• DONT 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-1
-------------I------V--LI--I--TA- DENV-3
-------------V---LN-L--MV--I--SA- DENV-4
-----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
17
(No Transcript)
18
(No Transcript)
19

• HOW DO THESE THINGS WORK?

20
(No Transcript)
21
(No Transcript)
22
(No Transcript)
23
Next Steps?