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 #
2P01AI057788-06
Application #
7774784
Study Section
Special Emphasis Panel (ZAI1-GPJ-M (S1))
Project Start
2010-04-15
Project End
2015-03-31
Budget Start
2010-04-15
Budget End
2011-03-31
Support Year
6
Fiscal Year
2010
Total Cost
$284,952
Indirect Cost
Name
Baylor College of Medicine
Department
Type
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Alvarado, Gabriela; Ettayebi, Khalil; Atmar, Robert L et al. (2018) Human Monoclonal Antibodies That Neutralize Pandemic GII.4 Noroviruses. Gastroenterology 155:1898-1907
Costantini, Veronica; Morantz, Esther K; Browne, Hannah et al. (2018) Human Norovirus Replication in Human Intestinal Enteroids as Model to Evaluate Virus Inactivation. Emerg Infect Dis 24:1453-1464
Bányai, Krisztián; Estes, Mary K; Martella, Vito et al. (2018) Viral gastroenteritis. Lancet 392:175-186
Cortes-Penfield, Nicolas W; Ramani, Sasirekha; Estes, Mary K et al. (2017) Prospects and Challenges in the Development of a Norovirus Vaccine. Clin Ther 39:1537-1549
Ramani, Sasirekha; Neill, Frederick H; Ferreira, Jennifer et al. (2017) B-Cell Responses to Intramuscular Administration of a Bivalent Virus-Like Particle Human Norovirus Vaccine. Clin Vaccine Immunol 24:
Hurwitz, Amy M; Huang, Wanzhi; Estes, Mary K et al. (2017) Deep sequencing of phage-displayed peptide libraries reveals sequence motif that detects norovirus. Protein Eng Des Sel 30:129-139
Sharma, Sumit; Carlsson, Beatrice; Czakó, Rita et al. (2017) Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades. J Virol 91:
Shanker, Sreejesh; Hu, Liya; Ramani, Sasirekha et al. (2017) Structural features of glycan recognition among viral pathogens. Curr Opin Struct Biol 44:211-218
Zou, Winnie Y; Blutt, Sarah E; Crawford, Sue E et al. (2017) Human Intestinal Enteroids: New Models to Study Gastrointestinal Virus Infections. Methods Mol Biol :
Yu, Huimin; Hasan, Nesrin M; In, Julie G et al. (2017) The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology. Annu Rev Physiol 79:291-312

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