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Glucosylceramide synthase inhibitors prevent replication of SARS-CoV-2 and influenza virus

Einat B Vitner1, Hagit Achdout1, Roy Avraham1

  • 1Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.

The Journal of Biological Chemistry
|February 27, 2021
PubMed

Insights

Two glucosylceramide synthase inhibitors show promise in combating viral infections. These compounds effectively inhibit the replication of SARS-CoV-2 and influenza viruses, suggesting a new therapeutic avenue.

Area of Science:

  • Virology
  • Cell Biology
  • Drug Discovery

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant global health threat.
  • While vaccines are crucial, effective antiviral treatments are essential for managing COVID-19 and other viral infections.
  • Viral replication depends on host cell membrane dynamics, presenting a potential therapeutic target.

Purpose of the Study:

  • To investigate glycosphingolipid synthesis as a novel therapeutic target against SARS-CoV-2.
  • To evaluate the antiviral efficacy of specific glucosylceramide synthase (GCS) inhibitors against SARS-CoV-2 and influenza viruses.

Main Methods:

  • Utilized two GCS inhibitors: Genz-123346 (analogue of Cerdelga) and GENZ-667161 (analogue of venglustat).
  • Assessed the impact of these inhibitors on the replication of SARS-CoV-2 and influenza virus A/PR/8/34 (H1N1) in host cells.

Main Results:

  • Both GCS inhibitors demonstrated significant inhibition of SARS-CoV-2 replication.
  • The GCS inhibitors were also effective in disrupting the replication of influenza virus A/PR/8/34 (H1N1).

Conclusions:

  • Glycosphingolipid synthesis is essential for supporting the life cycles of various viruses.
  • GCS inhibitors represent a promising class of compounds for further development as broad-spectrum antiviral therapies.
Keywords:
COVID-19SARS-CoV-2antiviral drugsglucosylceramideglucosylceramide synthasesphingolipids

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