The Protein and Small Molecule Chemistry Core (Core C) will provide instrumentation, expertise and service related to the cloning, expression and purification of viral proteins and virus-like-particles (VLPs) as needed by each of the three major projects. In addition, the Core will provide chemical synthesis support for the small molecule inhibitor discovery efforts proposed in Projects 1 and 3. This core will provide the following specific functions: (1) cloning of wild-type and mutant genes encoding viral proteins into bacterial and insect expressions systems;(2) purification of viral proteins;(3) expression, purification and characterization of VLPs;(4) quantitation of interactions with antibodies, polysaccharides and small molecules;(5) synthesis of peptide arrays for diagnostics assays proposed in Project 1;(6) synthesis of small molecules to examine structure-activity relationships and increase potency of candidate molecules developed in Projects 1 and 3.

Public Health Relevance

The Protein and Small Molecule Chemistry Core will facilitate the discovery and development of molecules to be used as diagnostics or therapeutics for norovirus infections. The development of new diagnostics and therapeutics would have a positive impact on public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI057788-09
Application #
8450101
Study Section
Special Emphasis Panel (ZAI1-GPJ-M)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
9
Fiscal Year
2013
Total Cost
$254,642
Indirect Cost
$88,751
Name
Baylor College of Medicine
Department
Type
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Ajami, Nadim J; Kavanagh, Owen V; Ramani, Sasirekha et al. (2014) Seroepidemiology of norovirus-associated travelers' diarrhea. J Travel Med 21:6-11
Qu, Lin; Vongpunsawad, Sompong; Atmar, Robert L et al. (2014) Development of a Gaussia luciferase-based human norovirus protease reporter system: cell type-specific profile of Norwalk virus protease precursors and evaluation of inhibitors. J Virol 88:10312-26
Venkataram Prasad, B V; Air, Gillian M (2014) Editorial overview: virus-glycan interactions and pathogenesis. Curr Opin Virol 7:v-vi
Atmar, Robert L; Opekun, Antone R; Gilger, Mark A et al. (2014) Determination of the 50% human infectious dose for Norwalk virus. J Infect Dis 209:1016-22
Huang, Wanzhi; Samanta, Moumita; Crawford, Sue E et al. (2014) Identification of human single-chain antibodies with broad reactivity for noroviruses. Protein Eng Des Sel 27:339-49
Katayama, Kazuhiko; Murakami, Kosuke; Sharp, Tyler M et al. (2014) Plasmid-based human norovirus reverse genetics system produces reporter-tagged progeny virus containing infectious genomic RNA. Proc Natl Acad Sci U S A 111:E4043-52
Ramani, Sasirekha; Atmar, Robert L; Estes, Mary K (2014) Epidemiology of human noroviruses and updates on vaccine development. Curr Opin Gastroenterol 30:25-33
Shanker, Sreejesh; Czako, Rita; Sankaran, Banumathi et al. (2014) Structural analysis of determinants of histo-blood group antigen binding specificity in genogroup I noroviruses. J Virol 88:6168-80
Venkataram Prasad, B V; Shanker, Sreejesh; Hu, Liya et al. (2014) Structural basis of glycan interaction in gastroenteric viral pathogens. Curr Opin Virol 7:119-27
Rogers, Jennifer D; Ajami, Nadim J; Fryszczyn, Bartlomiej G et al. (2013) Identification and characterization of a peptide affinity reagent for detection of noroviruses in clinical samples. J Clin Microbiol 51:1803-8

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