Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production

Natalia Fintelman-Rodrigues; Carolina Q. Sacramento; Carlyle Ribeiro Lima; Franklin Souza da Silva; André C. Ferreira; Mayara Mattos; Caroline S. de Freitas; Vinicius Cardoso Soares; Suelen da Silva Gomes Dias; Jairo R. Temerozo; Milene Miranda; Aline R. Matos; Fernando A. Bozza; Nicolas Carels; Carlos Roberto Alves; Marilda M. Siqueira; Patrícia T. Bozza; Thiago Moreno L. Souza

ATV/RTV and CQ were similarly efficient to inhibit viral replication in the human monocytes ( Figure 7A ). Virus infection increased cellular mortality by 75%, which was prevented by ATV, at both doses tested, and by ATV/RTV, at 10 μM ( Figure 7B ). As a control, detergent treatment completely destroyed all cells ( Figure 7B ). Moreover, we observed that infections by SARS-CoV-2 triggered the expected increase in the IL-6 levels in the culture supernatant, which ranged from 20-to 60-fold depending on the cell donor ( Figure 7C , open circles in nil-treated cells). The virus-induced enhancement of IL-6 levels were significantly prevented by treatment with ATV at 10 µM, ATV/RTV at both 1 and 10 µM and CQ at 10 µM ( Figure 7C ). Another biomarker of uncontrolled pro-inflammatory cytokine response, TNF-α, was up-regulated 40-fold during virus infection ( Figure 7D ). Only the combination of ATV/RTV could significantly prevent the induction of TNF-α release ( Figure 7D ). Altogether, our results confirm that ATV and ATV/RTV should not be ignored as an additional therapeutic option against COVID-19.