The severity of the global COVID-19 pandemic poses an urgent need for the development of efficient therapeutic strategies. To complete the available therapeutic arsenal, targeting the SARS-CoV-2 genome by antisense RNA therapy should be deeply investigated. We designed in silico antisense oligonucleotides (ASO) targeting viral genome to block the viral replication and transcription. The objective of the project is to validate the best ASO firstly by in vitro experiments on infected Vero E6 cultures, and secondly to test the best oligonucleotides antisense in vivo on infected animal model to perform a preclinical trial.