Development of a Cell-Based High-Throughput Functional Screening Assay To Study Host-Virus (COVID-19) Interaction

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Despite the needs for prophylactic and therapeutic treatments, no drug or vaccine has yet been approved for the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among the options envisaged to control or prevent the spread of SARS-CoV-2, blocking its cell entry with neutralizing antibodies, peptide blockers or protease inhibitors targeting viral (spike protein) and host membrane proteins (ACE2 and TMPRSS2) may be extremely effective to combat the invading virus. Unfortunately, due to the safety concerns related to viral replication, SARS-CoV-2 is classified as a BSL3 agent and its manipulation requires high-containment laboratories and trained personnel. In response to the current pandemic, the goal of this collaborative research project submitted with the partner Immune Biosolutions, a biotech company focusing on the discovery, engineering and development of humanized chicken antibodies for oncology and infectious diseases, is to develop a safe and accurate lentiviral model of SARS-CoV-2 infection that will allow high-throughput screening and validation of COVID-19 innovative therapeutics in BSL2 laboratories. To this aim, we propose (1) to incorporate the SARS-CoV-2 spike protein (SARS-CoV-2 S) in lentiviral pseudovirions and implement a robust and reproducible fluorescence detection-based functional assay for high-throughput screening and quantification of antiviral drug efficacy through the monitoring of permissive cell infection by eGFP-positive pseudoviral particles; and (2) to screen lung, gastrointestinal and brain cell types for their susceptibility to pseudovirus infection. It is anticipated that this lentiviral cell-based functional platform will accelerate the discovery and validation of new solutions to fight against current and future coronavirus infections.