Development of a Cryo-EM pipeline for ligand discovery for SARS-CoV-2 Spike protein

• Grant number: 23/04847-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2023
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Rodrigo Villares Portugal
• Grantee: Matheus Pintor Baptista
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated research grant: 20/06062-1 - Biological complexes in action, in vitro and in silico (Exploiting Big-Data in Cryo-EM), AP.TEM

Abstract

Single-particle cryo-EM has achieved a resolution level that can be used in drug discovery. This approach is of paramount importance for understanding the mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike (S) protein, the surface glycoprotein involved in receptor recognition, viral attachment, and entry into host cells, is a key target for vaccine and therapeutic research, being the focus of a flood of recent publications. For obtaining high-resolution results, the various cryo-EM procedures, including the data collection and data processing, must be optimised. The aim of this project is to establish a pipeline for ligand discovery applied to the SARS-CoV-2 S-protein. The project will include several activities: establishing expression and purification protocols; optimizing specimen preparation, data collection and data processing; structural analysis with ligands, natural products and fragments. If successful, this pipeline could be used for screening and become available to the community. (AU)