Ultrastructural characterisation of the anti-flaviviral compounds on the biogenesis of Zika virus replication organelles

• Grant number: 25/21936-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: February 01, 2026
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Glaucius Oliva
• Grantee: Isabela Dolci
• Supervisor: Jonathan Grimes
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Institution abroad: University of Oxford, England
• Associated to the scholarship: 22/16111-5 - Discovery and development of antiviral candidates against the Zika Virus protease NS2B-NS3pro, BP.DD

Abstract

Zika virus (ZIKV) is a positive-sense, single-stranded RNA virus transmitted primarily by Aedes mosquitoes and associated with severe clinical outcomes, including congenital Zika syndrome and neurological complications. Despite its public health relevance, no specific antivirals are currently available, highlighting the need for alternative therapeutic strategies. During infection, ZIKV non- structural proteins remodel endoplasmic reticulum membranes to form replication organelles, specialized compartments that concentrate viral proteins and RNA to support efficient genome replication. This project aims to investigate the ultrastructural organization of ZIKV replication organelles and to evaluate the potential effects of selected antiviral compounds. Initially, the timing of compound addition will be optimized in both replicon-harboring and infected cells to maximize the detection of antiviral effects. Cryo-electron tomography (cryo-ET) will then be applied to visualize intact replication organelles under near-native conditions. Quantitative analysis using command-line tools and custom scripts will assess structural features such as organelle size, shape, and spatial organization, comparing treated and untreated samples to identify compound-induced modifications. The internship at the Oxford Particle Imaging Centre (OPIC) under Prof. Jonathan Grimes, with co- orientation by postdoctoral researcher Dr. Pranav Shah, will provide access to advanced cryo-ET instrumentation and expertise, enabling the acquisition of high-quality datasets. The knowledge and technical skills gained are expected to support the implementation of cryo-ET approaches at IFSC/USP, contributing to the development of structural biology research in Brazil and advancing understanding of ZIKV replication and antiviral mechanisms. (AU)