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Antiviral Res . Cathepsin inhibitors nitroxoline and its derivatives inhibit SARS-CoV-2 infection

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  • Antiviral Res . Cathepsin inhibitors nitroxoline and its derivatives inhibit SARS-CoV-2 infection

    Antiviral Res


    . 2023 Jun 22;105655.
    doi: 10.1016/j.antiviral.2023.105655. Online ahead of print. Cathepsin inhibitors nitroxoline and its derivatives inhibit SARS-CoV-2 infection

    Rafaela Milan Bonotto 1 , Ana Mitrović 2 , Izidor Sosič 3 , Pamela Martinez-Orellana 1 , Federica Dattola 1 , Stanislav Gobec 3 , Janko Kos 4 , Alessandro Marcello 5



    AffiliationsAbstract

    The severity of the SARS-CoV-2 pandemic and the recurring (re)emergence of viruses prompted the development of new therapeutic approaches that target viral and host factors crucial for viral infection. Among them, host peptidases cathepsins B and L have been described as essential enzymes during SARS-CoV-2 entry. In this study, we evaluated the effect of potent selective cathepsin inhibitors as antiviral agents. We demonstrated that selective cathepsin B inhibitors, such as the antimicrobial agent nitroxoline and its derivatives, impair SARS-CoV-2 infection in vitro. Antiviral activity observed at early stage of virus entry was cell-type dependent and correlated well with the intracellular content and enzymatic function of cathepsins B or L. Furthermore, tested inhibitors were effective against the ancestral SARS-CoV-2 D614 as well as against the more recent BA.1_4 (Omicron). Taken together, our results highlight the important role of host cysteine cathepsin B in SARS-CoV-2 virus entry and show that cathepsin-specific inhibitors, such as nitroxoline and its derivatives, could be used to treat COVID-19. Finally, these results also suggest that nitroxoline has potential to be further explored as repurposed drug in antiviral therapy.

    Keywords: COVID-19; Cathepsin; Coronavirus; Drug repurposing; Inhibition; Nitroxoline; SARS-CoV-2.

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