(1061-B) Accelerating Antiviral Therapeutic Discovery Against SARS-CoV-2, its variants and Potential Emerging Pathogens

Abstract: The Chemogenomic and Biological Screening Core Facility (PF-CCB) at Institut Pasteur Paris serves as a pivotal resource in drug discovery, driving the development of novel therapeutics and unraveling molecular pathways. During the COVID-19 pandemic, PF-CCB quickly implemented screening strategies to identify active molecules against authentic SARS-CoV-2. A robust medium-throughput screening assay, in 384-well format in a BSL3 environment, was developed enabling the evaluation of the anti-viral properties (IC50 and therapeutical index) of 200 molecules per week. Leveraging intra-campus collaborations, an in vivo Syrian hamster model was established to assess the efficacy of the most promising molecules against diverse SARS-CoV-2 variants. Through a compelling case study evaluating therapeutic monoclonal antibodies, the platform's efficacy and translational potential are demonstrated, corroborated by subsequent clinical trials. Building on this success, the screening pipeline has been adapted for the evaluation of new molecules against arboviruses and respiratory syncytial virus (RSV), emphasizing proactive pandemic preparedness. Through an integrated approach spanning molecular, cellular, and in vivo methodologies, PF-CCB accelerates the discovery and development of antiviral therapeutics, contributing to global initiatives in infectious disease control and public health protection.