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Investigation of the molecular mechanisms of the infection processes of human cells by dengue virus

Grant number: 08/11706-3
Support type:Research Projects - Thematic Grants
Duration: February 01, 2010 - January 31, 2014
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Leo Degreve
Grantee:Leo Degreve
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. researchers:Antonio Caliri ; Glaucia Maria da Silva ; Luis Gustavo Dias ; Maria Cristina Nonato
Associated scholarship(s):13/00927-7 - Molecular dynamics simulations for the identification of bioactive molecules: inhibitors of the interaction between the dengue virus envelope glycoprotein and cellular C-type lectins, BP.DD
10/01538-6 - Dynamic ánd conformational study of protein Calgranulin C (S100A12) ín interaction with bivalent ions ánd RAGE receptor, BP.MS

Abstract

The Dengue and Hemorrhagic Dengue are acute febrile diseases that take ill to the tropical populations but just begin to invade the temperate zones of Earth. The Dengue is considered a very important disease for the development of a vaccine and antiviral drugs due to its socio-economic impact. In the nowadays, 2.5 billion persons must be living inside the risk areas of the epidemic transmission. Also, 50 to 100 million persons are infected per year in the world of which one hundred thousand of cases are hemorrhagic dengue with a fatality rate about 1 to 5%. In 2007, 560000 Dengue cases occurred in the Brazil of which 1500 were hemorrhagic dengue with high rate of fatality. 1700 scientists in Brazil have devoted time for the understanding and control of the viral infection, development and test of vaccines, clinical treatment, interactions between virus and antibodies, relationship between genetic factors and disease intensity. It turns out that a broad and diverse range of concepts and views provided by subject fields as virology, public health, infectology, biochemistry, molecular biology, among others, have been necessary and applied to Dengue. From a reductionist point of view, the Dengue virus is a molecular machine composed by (only) 10 proteins: C, prM, E, NS1, NS2A, NS2B, NS4A, NS4B and NS5. Ones are structural proteins; others are proteins transporting viral genetic material for inside and outside the cell and proteins working on virus replication. The project goal is shed light on the molecular mechanism of fusion between the Dengue virus and its host cell and the molecular mechanism related to virus replication and its inhibition. The mechanism will be studied with a sort of tridimensional information initially extracted from the crystallography and electronic microscopy of the Dengue proteins, cellular receptors, complex of viral protein and antiviral molecule, and so on. Several computational techniques must be used in the project, ranging from molecular dynamics by all atom force field, coarse-grained modeling, chemometrics methods and linear-interaction-energy to the ab initio and DFT calculations for accurate evaluation of local interactions. An internet site will be developed in an appropriated audiovisual form to produce and present information, papers, videos by the Portal Paulista da Dengue. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DEGREVE, LEO; FUZO, CARLOS A.; CALIRI, ANTONIO. Extended secondary structures in proteins. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1844, n. 2, p. 384-388, FEB 2014. Web of Science Citations: 0.
SOARES, R. O. S.; CALIRI, A. Stereochemical features of the envelope protein Domain III of dengue virus reveals putative antigenic site in the five-fold symmetry axis. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1834, n. 1, p. 221-230, JAN 2013. Web of Science Citations: 9.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.