Structural characterization of Chikungunya Virus proteins and the search for antiviral agents

• Grant number: 17/07229-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2017
• End date: February 28, 2018
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Glaucius Oliva
• Grantee: Gustavo Machado Alvares de Lima
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

Chikungunya fever, caused by the Chikungunya Virus (CHIKV), is an arbovirose transmitted to humans by the bite of female infected mosquitoes, commonly the Aedes aegypti. Symptoms, related to the patient's gender and age, include rash, vomiting, joint and musculoskeletal pain, edema, fever, and neurological problems in adults, such as Guillain-Barre syndrome. In addition, there are reports, albeit rare, of spontaneous abortion in infected pregnant women. The absence of effective treatment against the disease, associated with the debilitating period caused by acute pain, creates the need to intensify studies that may lead to new candidates for CHIKV drugs or vaccines. To date, there are no effective treatments or forms of virus eradication, and the prevention and control of transmitter mosquito populations are the only ways to combat CHIKV. CHIKV is a positive-strand RNA virus of the genus Alphavirus, whose genetic material encodes two polyproteins, one structural and one non-structural, which after cleavage becomes nine mature proteins. Three of these proteins form the viral envelope (E1, E2 and E3), one the capsid (protein C), and another four are involved in the viral replication process. The envelope proteins E1, E2 and E3, as well as the proteins nsP2 domain C9-peptidase, nsP3 Macrodomain and protein C already have their three-dimensional structures solved. This project proposes to study primarily proteins whose structures are not available using techniques such as molecular biology and X-ray crystallography. Furthermore, proteins with structures already described will be the object of recombinant expression and crystallization, in order to expand the current knowledge about them, allowing the search for new inhibitors candidates for antiviral drugs, using the Structure Based Drug Design and Fragment Based Drug Design. This project is tied to the FAPESP's project CIBFar/CEPID, and also aims to establish a base in the group for CHIKV studies, which already has experience with other arboviruses.