TY - JOUR T1 - Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production JF - bioRxiv DO - 10.1101/2020.04.04.020925 SP - 2020.04.04.020925 AU - Natalia Fintelman-Rodrigues AU - Carolina Q. Sacramento AU - Carlyle Ribeiro Lima AU - Franklin Souza da Silva AU - André C. Ferreira AU - Mayara Mattos AU - Caroline S. de Freitas AU - Vinicius Cardoso Soares AU - Suelen da Silva Gomes Dias AU - Jairo R. Temerozo AU - Milene Miranda AU - Aline R. Matos AU - Fernando A. Bozza AU - Nicolas Carels AU - Carlos Roberto Alves AU - Marilda M. Siqueira AU - Patrícia T. Bozza AU - Thiago Moreno L. Souza Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/06/2020.04.04.020925.abstract N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease (COVID-19) would allow the rapid implementation of potentially life-saving procedures. The major protease (Mpro) of SARS-CoV-2 is considered a promising target, based on previous results from related CoVs with lopinavir (LPV), an HIV protease inhibitor. However, limited evidence exists for other clinically approved antiretroviral protease inhibitors, such as atazanavir (ATV). ATV is of high interest because of its bioavailability within the respiratory tract. Our results show that ATV could dock in the active site of SARS-CoV-2 Mpro, with greater strength than LPV. ATV blocked Mpro activity. We confirmed that ATV inhibits SARS-CoV-2 replication, alone or in combination with ritonavir (RTV) in Vero cells, human pulmonary epithelial cell line and primary monocytes, impairing virus-induced enhancement of IL-6 and TNF-α levels. Together, our data strongly suggest that ATV and ATV/RTV should be considered among the candidate repurposed drugs undergoing clinical trials in the fight against COVID-19. ER -