RT Journal Article SR Electronic T1 The in vitro antiviral activity of the anti-hepatitis C virus (HCV) drugs daclatasvir and sofosbuvir against SARS-CoV-2 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.15.153411 DO 10.1101/2020.06.15.153411 A1 Carolina Q. Sacramento A1 Natalia Fintelman-Rodrigues A1 Jairo R. Temerozo A1 Suelen da Silva Gomes Dias A1 André C. Ferreira A1 Mayara Mattos A1 Camila R. R. Pão A1 Caroline S. de Freitas A1 Vinicius Cardoso Soares A1 Fernando A. Bozza A1 Dumith Chequer Bou-Habib A1 Patrícia T. Bozza A1 Thiago Moreno L. Souza YR 2020 UL http://biorxiv.org/content/early/2020/06/16/2020.06.15.153411.abstract AB The infection by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes major public health concern and economic burden. Although clinically approved drugs have been repurposed to treat individuals with 2019 Coronavirus disease (COVID-19), the lack of safety studies and limited efficiency as well jeopardize clinical benefits. Daclatasvir and sofosbuvir (SFV) are clinically approved direct-acting antivirals (DAA) against hepatitis C virus (HCV), with satisfactory safety profile. In the HCV replicative cycle, daclatasvir and SFV target the viral enzymes NS5A and NS5B, respectively. NS5A is endowed with pleotropic activities, which overlap with several proteins from SARS-CoV-2. HCV NS5B and SARS-CoV-2 nsp12 are RNA polymerases that share homology in the nucleotide uptake channel. These characteristics of the HCV and SARS-CoV-2 motivated us to further study the activity of daclatasvir and SFV against the new coronavirus. Daclatasvir consistently inhibited the production of infectious SARS-CoV-2 virus particles in Vero cells, in the hepatoma cell line HuH-7 and in type II pneumocytes (Calu-3), with potencies of 0.8, 0.6 and 1.1 μM, respectively. Daclatasvir targeted early events during SARS-CoV-2 replication cycle and prevented the induction of IL-6 and TNF-α, inflammatory mediators associated with the cytokine storm typical of SARS-CoV-2 infection. Sofosbuvir, although inactive in Vero cells, displayed EC50 values of 6.2 and 9.5 μM in HuH-7 and Calu-3 cells, respectively. Our data point to additional antiviral candidates, in especial daclatasvir, among drugs overlooked for COVID-19, that could immediately enter clinical trials.Competing Interest StatementThe authors have declared no competing interest.