tetano
Editor, Senior Moderator
J Biol Chem
. 2021 Feb 24;100470.
doi: 10.1016/j.jbc.2021.100470. Online ahead of print.
Glucosylceramide synthase inhibitors prevent replication of SARS-CoV-2 and Influenza virus
Einat B Vitner[SUP] 1 [/SUP], Hagit Achdout[SUP] 2 [/SUP], Roy Avraham[SUP] 2 [/SUP], Boaz Politi[SUP] 2 [/SUP], Lilach Cherry[SUP] 2 [/SUP], Hadas Tamir[SUP] 2 [/SUP], Yfat Yahalom-Ronen[SUP] 2 [/SUP], Nir Paran[SUP] 2 [/SUP], Sharon Melamed[SUP] 2 [/SUP], Noam Erez[SUP] 2 [/SUP], Tomer Israely[SUP] 2 [/SUP]
Affiliations
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 lifecycle, 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 FDA-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.
Keywords: COVID-19; GlucosylCeramide Synthase; Glucosylceramide; SARS-CoV-2; Sphingolipids; antiviral drugs.
. 2021 Feb 24;100470.
doi: 10.1016/j.jbc.2021.100470. Online ahead of print.
Glucosylceramide synthase inhibitors prevent replication of SARS-CoV-2 and Influenza virus
Einat B Vitner[SUP] 1 [/SUP], Hagit Achdout[SUP] 2 [/SUP], Roy Avraham[SUP] 2 [/SUP], Boaz Politi[SUP] 2 [/SUP], Lilach Cherry[SUP] 2 [/SUP], Hadas Tamir[SUP] 2 [/SUP], Yfat Yahalom-Ronen[SUP] 2 [/SUP], Nir Paran[SUP] 2 [/SUP], Sharon Melamed[SUP] 2 [/SUP], Noam Erez[SUP] 2 [/SUP], Tomer Israely[SUP] 2 [/SUP]
Affiliations
- PMID: 33639165
- DOI: 10.1016/j.jbc.2021.100470
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 lifecycle, 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 FDA-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.
Keywords: COVID-19; GlucosylCeramide Synthase; Glucosylceramide; SARS-CoV-2; Sphingolipids; antiviral drugs.