tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Ana Mitrović[SUP] 2 [/SUP], Izidor Sosič[SUP] 3 [/SUP], Pamela Martinez-Orellana[SUP] 1 [/SUP], Federica Dattola[SUP] 1 [/SUP], Stanislav Gobec[SUP] 3 [/SUP], Janko Kos[SUP] 4 [/SUP], Alessandro Marcello[SUP] 5 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Ana Mitrović[SUP] 2 [/SUP], Izidor Sosič[SUP] 3 [/SUP], Pamela Martinez-Orellana[SUP] 1 [/SUP], Federica Dattola[SUP] 1 [/SUP], Stanislav Gobec[SUP] 3 [/SUP], Janko Kos[SUP] 4 [/SUP], Alessandro Marcello[SUP] 5 [/SUP]
Affiliations
- PMID: 37355023
- DOI: 10.1016/j.antiviral.2023.105655
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.