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Glucosylceramide synthase inhibitors prevent replication of SARS-CoV-2 and influenza virus.
Vitner, Einat B; Achdout, Hagit; Avraham, Roy; Politi, Boaz; Cherry, Lilach; Tamir, Hadas; Yahalom-Ronen, Yfat; Paran, Nir; Melamed, Sharon; Erez, Noam; Israely, Tomer.
  • Vitner EB; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel. Electronic address: einatv@iibr.gov.il.
  • Achdout H; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Avraham R; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Politi B; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Cherry L; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Tamir H; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Yahalom-Ronen Y; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Paran N; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Melamed S; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Erez N; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
  • Israely T; Departments of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
J Biol Chem ; 296: 100470, 2021.
Article in English | MEDLINE | ID: covidwho-1101336
ABSTRACT
The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health. Vaccines are ideal solutions to prevent infection, but treatments are also needed for those who have contracted the virus to limit negative outcomes, when vaccines are not applicable. Viruses must cross host cell membranes during their life cycle, creating a dependency on processes involving membrane dynamics. Thus, in this study, we examined whether the synthetic machinery for glycosphingolipids, biologically active components of cell membranes, can serve as a therapeutic target to combat SARS-CoV-2. We examined the antiviral effect of two specific inhibitors of glucosylceramide synthase (GCS) (i) Genz-123346, an analogue of the United States Food and Drug Administration-approved drug Cerdelga and (ii) GENZ-667161, an analogue of venglustat, which is currently under phase III clinical trials. We found that both GCS inhibitors inhibit replication of SARS-CoV-2. Moreover, these inhibitors also disrupt replication of influenza virus A/PR/8/34 (H1N1). Our data imply that synthesis of glycosphingolipids is necessary to support viral life cycles and suggest that GCS inhibitors should be further explored as antiviral therapies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pyrrolidines / Quinuclidines / Carbamates / Glycosphingolipids / Dioxanes / Influenza A Virus, H1N1 Subtype / SARS-CoV-2 / Glucosyltransferases Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines Language: English Journal: J Biol Chem Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pyrrolidines / Quinuclidines / Carbamates / Glycosphingolipids / Dioxanes / Influenza A Virus, H1N1 Subtype / SARS-CoV-2 / Glucosyltransferases Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines Language: English Journal: J Biol Chem Year: 2021 Document Type: Article