Corpus overview


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MeSH Disease

HGNC Genes

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Transmission

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    Antiviral activity of Glucosylceramide synthase inhibitors against SARS-CoV-2 and other RNA virus infections

    Authors: Einat B. Vitner; Roy Avraham; Hagit Achdout; Hadas Tamir; Avi Agami; Lilach Cherry; Yfat Yahalom-Ronen; Boaz Politi; Noam Erez; Sharon Melamed; Nir Paran; Tomer Israely

    doi:10.1101/2020.05.18.103283 Date: 2020-05-19 Source: bioRxiv

    The need for antiviral drugs is real and relevant. Broad spectrum antiviral drugs have a particular advantage when dealing with rapid disease outbreaks, such as the current COVID-19 MESHD pandemic. Since viruses are completely dependent on internal cell mechanisms, they must cross cell membranes during their lifecycle, creating a dependence on processes involving membrane dynamics. Thus, in this study we examined whether the synthesis of glycosphingolipids, biologically active components of cell membranes, can serve as an antiviral therapeutic target. We examined the antiviral effect of two specific inhibitors of GlucosylCeramide MESHD synthase (GCS); (i) Genz-123346, an analogue of the FDA-approved drug Cerdelga(R), (ii) GENZ-667161, an analogue of venglustat which is currently under phase III clinical trials. We found that both GCS inhibitors inhibit the replication of four different enveloped RNA viruses of different genus, organ-target and transmission TRANS route: (i) Neuroinvasive Sindbis virus (SVNI), (ii) West Nile virus (WNV), (iii) Influenza A virus, and (iv) SARS-CoV-2. Moreover, GCS inhibitors significantly increase the survival rate of SVNI-infected MESHD mice. Our data suggest that GCS inhibitors can potentially serve as a broad-spectrum antiviral therapy and should be further examined in preclinical and clinical trial. Analogues of the specific compounds tested have already been studied clinically, implying they can be fast-tracked for public use. With the current COVID-19 MESHD pandemic, this may be particularly relevant to SARS-CoV-2 infection MESHD. One Sentence SummaryAn analogue of Cerdelga(R), an FDA-approved drug, is effective against a broad range of RNA-viruses including the newly emerging SARS-CoV-2.

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MeSH Disease
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