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ATAZANAVIR, ALONE OR IN COMBINATION WITH RITONAVIR, INHIBITS SARS-COV-2 REPLICATION AND PROINFLAMMATORY CYTOKINE PRODUCTION
Ritonavir
Inibição
SARS-CoV-2
Replicação
Produção de citocina inflamatória
COVID-19
https://www.arca.fiocruz.br/handle/icict/44755
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Abstract
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 dentification 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. Extensive use of atazanavir (ATV) as antiretroviral and previous evidencesuggesting its bioavailability within the respiratory tract prompted us to study this molecule against SARS-CoV-2. Our results show that ATV could dock in the active site of SARS - CoV-2 Mpro, with greater strength than LPV, blocking Mpro activity. We confirmed that 50 ATV inhibits SARS-CoV-2 replication, alone or in combination with ritonavir (RTV) in Vero cells and human pulmonary epithelial cell line. ATV/RTV also impaired virusinduced 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.
Keywords in Portuguese
AtazanavirRitonavir
Inibição
SARS-CoV-2
Replicação
Produção de citocina inflamatória
COVID-19
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