α-glucosidase inhibitors as host-directed antiviral agents with potential for the treatment of COVID-19

Biochem Soc Trans. 2020 Jun 30;48(3):1287-1295. doi: 10.1042/BST20200505.

Abstract

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, has pushed the health systems of many countries to breaking point and precipitated social distancing measures that have crippled economic activities across the globe. A return to normality is unlikely until effective therapeutics and a vaccine are available. The immediacy of this problem suggests that drug strategies should focus on repurposing approved drugs or late-stage clinical candidates, as these have the shortest path to use in the clinic. Here, we review and discuss the role of host cell N-glycosylation pathways to virus replication and the drugs available to disrupt these pathways. In particular, we make a case for evaluation of the well-tolerated drugs miglitol, celgosivir and especially miglustat for the treatment of COVID-19.

Keywords: COVID-19; SARS-CoV-2; antiviral; drug repurposing; glycosylation; therapeutic.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Betacoronavirus / chemistry*
  • COVID-19
  • Calnexin / metabolism
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / metabolism*
  • Coronavirus Infections / virology
  • Drug Repositioning / methods*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Glycoside Hydrolase Inhibitors / therapeutic use
  • Glycosylation / drug effects
  • Host-Pathogen Interactions
  • Humans
  • Pandemics
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / metabolism*
  • Pneumonia, Viral / virology
  • Protein Folding / drug effects
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / metabolism
  • Virus Replication / drug effects
  • alpha-Glucosidases / metabolism

Substances

  • Antiviral Agents
  • CANX protein, human
  • Glycoside Hydrolase Inhibitors
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Calnexin
  • glucosidase I
  • alpha-Glucosidases