Caliciviruses consist of a family of viruses that infect humans and animals. Human caliciviruses called noroviruses cause gastrointestinal disease, with the disease burden being enormous in all age groups. Death can occur in young children and the elderly. Noroviruses cause almost all outbreaks (>95%) of nonbacterial foodborne and waterborne disease that result in 23 million cases of gastroenteritis annually in the US. Rehydration therapy is currently the only treatment for disease and hand washing may reduce transmission. Diagnosis is challenging because universal primers to detect the viral RNA genome are not available, and no rapid, broadly-reactive enzyme immunoassay is approved in the US. Effective antivirals could be useful to stop spread of virus in semi-closed environments and treat chronically infected individuals. This Program Project application integrates the efforts of a molecular virologist, a physician scientist, a biophysical chemist/microbiologist with expertise in proteomics, a structural biologist, and a newly recruited medicinal chemist interested in small molecule inhibitors. This integrated team will build on previous basic science experience and discoveries to allow rapid progress on current applied needs related to public health and understanding of viral pathogenesis. Project 1 will develop new, broadly-reactive diagnostic assays to detect noroviruses and identify lead antiviral compounds to inhibit key targets required for viral replication. Project 2 will develop methods to propagate noroviruses in cultured cells and dissect the molecular basis of host restriction of viral replication. Project 3 will pursue high resolution structural information on the viral capsid and viral proteins critical for genome replication to facilitate structure -based development and testing of antivirals. Each project is dependent on the experimental and intellectual contributions of 3 Core facilities: the Administration Core, Microscopy Core, and the Protein and Small Molecule Chemistry Core. Proposed, continued research by this Program Project team is expected to make new fundamental discoveries that will be important in the diagnosis, treatment, prevention and understanding of the biology of these epidemiologically significant human pathogens.

Public Health Relevance

Human caliciviruses cause gastrointestinal disease and the disease burden is enormous in all age groups. This Program Project grant proposes continued studies by a highly productive, integrated team of basic and clinical investigators to use multidisciplinary approaches to develop new tests and drugs for diagnosis, treatment and prevention of disease caused by these important human pathogens.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-GPJ-M (S1))
Program Officer
Cassels, Frederick J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
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

Showing the most recent 10 out of 47 publications