Molecular mechanisms underlying the recognition of the Dengue Virus envelope glycoprotein by the cellular lectin DC-SIGN and potential inhibitors of such interaction

• Grant number: 16/04958-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: September 21, 2016
• End date: September 05, 2017
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Antonio Caliri
• Grantee: Leandro Oliveira Bortot
• Supervisor: David Van der Spoel
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Uppsala University (UU), Sweden
• Associated to the scholarship: 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

Abstract

Dengue is a Neglected Tropical Disease that threatens half the world's population and against which there is no antivirals available for specific treatment. The attachment and internalization steps of the viral replication cycle are promising for the development of new therapeutic approaches. There are two essential elements for both of these steps: the viral envelope glycoprotein and cellular receptors that recognize it, such as DC-SIGN, and inhibiting their interaction may prevent further spreading of the infection inside the host. However, the molecular details about such event are unknown. In this context, we propose a project in which the molecular mechanisms underlying the interaction between the Dengue Virus glycosylated envelope glycoprotein and the cellular receptor DC-SIGN will be assessed using molecular dynamics simulations. Since the glycosylations displayed by the Dengue Virus are molecular patterns found in several pathogens, the proposed investigation will advance our basic knowledge about host-pathogen interactions at molecular level and contribute to drug design efforts. (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)

BORTOT, LEANDRO OLIVEIRA; BASHARDANESH, ZAHEDEH; VAN DER SPOEL, DAVID. Making Soup: Preparing and Validating Models of the Bacterial Cytoplasm for Molecular Simulation. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 60, n. 1, p. 322-331, JAN 2020. (13/00927-7, 16/04958-2)