tetano
Editor, Senior Moderator
Viruses
. 2021 Apr 30;13(5):808.
doi: 10.3390/v13050808.
Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2
Sreejith Rajasekharan[SUP] 1 [/SUP], Rafaela Milan Bonotto[SUP] 1 [/SUP], Lais Nascimento Alves[SUP] 1 [/SUP], Yvette Kazungu[SUP] 1 [/SUP], Monica Poggianella[SUP] 1 [/SUP], Pamela Martinez-Orellana[SUP] 1 [/SUP], Natasa Skoko[SUP] 2 [/SUP], Sulena Polez[SUP] 2 [/SUP], Alessandro Marcello[SUP] 1 [/SUP]
Affiliations
Abstract
Repurposing clinically available drugs to treat the new coronavirus disease 2019 (COVID-19) is an urgent need in the course of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) pandemic, as very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases, such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated in the micromolar range for SARS-CoV-2 in vitro. The drug acts at the post-entry level and leads to a marked decrease of viral proteins and release of infectious viruses. The mechanism resides in the inhibitory activity toward ?-glucosidases that are involved in the early stages of glycoprotein N-linked oligosaccharide processing in the endoplasmic reticulum, leading to a marked decrease of the viral Spike protein. Indeed, the antiviral potential of protein glycosylation inhibitors against SARS-CoV-2 is further highlighted by the low-micromolar activity of the investigational drug Celgosivir. These data point to a relevant role of this approach for the treatment of COVID-19.
Keywords: COVID-19; Celgosivir; Miglustat; SARS-CoV-2; antiviral; coronavirus; inhibitor; spike.
. 2021 Apr 30;13(5):808.
doi: 10.3390/v13050808.
Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2
Sreejith Rajasekharan[SUP] 1 [/SUP], Rafaela Milan Bonotto[SUP] 1 [/SUP], Lais Nascimento Alves[SUP] 1 [/SUP], Yvette Kazungu[SUP] 1 [/SUP], Monica Poggianella[SUP] 1 [/SUP], Pamela Martinez-Orellana[SUP] 1 [/SUP], Natasa Skoko[SUP] 2 [/SUP], Sulena Polez[SUP] 2 [/SUP], Alessandro Marcello[SUP] 1 [/SUP]
Affiliations
- PMID: 33946304
- DOI: 10.3390/v13050808
Abstract
Repurposing clinically available drugs to treat the new coronavirus disease 2019 (COVID-19) is an urgent need in the course of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) pandemic, as very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases, such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated in the micromolar range for SARS-CoV-2 in vitro. The drug acts at the post-entry level and leads to a marked decrease of viral proteins and release of infectious viruses. The mechanism resides in the inhibitory activity toward ?-glucosidases that are involved in the early stages of glycoprotein N-linked oligosaccharide processing in the endoplasmic reticulum, leading to a marked decrease of the viral Spike protein. Indeed, the antiviral potential of protein glycosylation inhibitors against SARS-CoV-2 is further highlighted by the low-micromolar activity of the investigational drug Celgosivir. These data point to a relevant role of this approach for the treatment of COVID-19.
Keywords: COVID-19; Celgosivir; Miglustat; SARS-CoV-2; antiviral; coronavirus; inhibitor; spike.