A whole-cell S. cerevisiae biosensor for the detection of ACE2-dependent viruses

• Grant number: 23/02347-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2024
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Gonçalo Amarante Guimarães Pereira
• Grantee: Gustavo Seguchi
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Coronaviruses are important human pathogens. Among them, SARS-CoV, HCoV-NL63 and SARS-CoV-2, the causal agents behind the SARS outbreak from 2003, the common cold and the current COVID-19 pandemic, utilise the human protein ACE2 as the main entry point to invade cells. Although the current detection systems (eg. The rapid antigen test and RT-qPCR) have played an important role in the management of the disease, they are hindered by important limitations that preclude efficient testing. The price and dependency on specialised equipment and personnel, or still, the compromised sensitivity for the detection of new variants as a result of mutated viral sequences, highlights the need for innovative solutions that surpass these difficulties. As such, this project proposes a viral detection system based on yeasts of the Saccharomyces cerevisiae species expressing ACE2 and a membrane receptor (AT1) for angiotensin II. The signal transduction in response to the virus would be indirect, triggered by the detection of Ang II concentration in the extracellular medium by AT1. It is known that ACE2 naturally converts Ang II to Ang 1-7, the hijacking of its enzymatic activity by the binding of the viral S protein would lead to an accumulation of its substrate and, consequently, to a greater reporter signal emission relative to the absence of the virus. Therefore, a yeast biosensor centred on the role of ACE2 stands as a rapid, innocuous and accessible viral detection tool, as well as being versatile and robust - given that other viruses or variants also utilise the same receptor for infection, this approach is not susceptible to antigenic escape.