SARS-CoV-2 replication in human ACE2-transgenic mice treated with daclatasvir

We examined the HCV nonstructural protein 5A (NS5A) inhibitor daclatasvir for potential repurposing against SARS-CoV-2 infection in transgenic miceexpressing human ACE2 (K18-hACE-2 mouse strain). Based on molecular docking, enzymatic assays and cellular-based studies, evidence was provided in favor of the compound possessing anti-exonuclease activity. Daclatasvir induced error-prone in vivo replication, prevented lethal SARS-CoV-2 replication, reduced cell death and inflammatory responses at a concentration that could allow further clinical development against COVID-19.