Small Molecule Antiviral Agents Against Flaviviruses

Award Information
Agency:
Department of Defense
Branch
Army
Amount:
$149,404.00
Award Year:
2012
Program:
SBIR
Phase:
Phase I
Contract:
W81XWH-12-C-0028
Award Id:
n/a
Agency Tracking Number:
A112-106-0883
Solicitation Year:
2011
Solicitation Topic Code:
A11-106
Solicitation Number:
2011.2
Small Business Information
300 George Street, Suite 309, New Haven, CT, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
142406110
Principal Investigator:
Michel Ledizet
PI/Senior Scientist
(203) 503-0383
mledizet@L2Dx.com
Business Contact:
Martin Mattessich
Managing Director
(203) 494-5288
mmattessich@L2Dx.com
Research Institution:
Stub




Abstract
Flaviviruses enter mammalian cells by a mechanism involving a structural rearrangement of the stem region of their envelope protein. The stem region establishes specific molecular contacts with amino acid residues of domain II of the rest of the envelope protein. Our hypothesis is that tetrapeptides that bind to the stem region of flaviviruses will block viral entry and could be used as human therapeutic agents. We will model the configuration of the stem region of West Nile virus (WNV) making contact with domain II, using a process that we used successfully with dengue virus (DV) serotype 1. We will then use advanced proprietary computational methods to design tetrapeptides predicted to bind the stem region in that configuration. The peptides predicted to bind the stem region with the highest affinity will be synthesized and tested in WNV and DV1-4 neutralizing assays. Because the stem region is conserved among flaviviruses, we expect that these peptides will be active against several flaviviruses of medical importance. Our preliminary results support the validity of our approach. We designed tetrapeptides predicted to bind the stem region of DV 1. We found that a portion of these peptides neutralized DV1, and also DV2 and WNV.

* information listed above is at the time of submission.

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