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Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2

Repurposing clinically available drugs to treat the new coronavirus disease 2019 (COVID-19) is an urgent need in the course of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) pandemic, as very few treatment options are available. The iminosugar Miglustat is a well-characterized drug f...

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Autores principales: Rajasekharan, Sreejith, Milan Bonotto, Rafaela, Nascimento Alves, Lais, Kazungu, Yvette, Poggianella, Monica, Martinez-Orellana, Pamela, Skoko, Natasa, Polez, Sulena, Marcello, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144969/
https://www.ncbi.nlm.nih.gov/pubmed/33946304
http://dx.doi.org/10.3390/v13050808
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author Rajasekharan, Sreejith
Milan Bonotto, Rafaela
Nascimento Alves, Lais
Kazungu, Yvette
Poggianella, Monica
Martinez-Orellana, Pamela
Skoko, Natasa
Polez, Sulena
Marcello, Alessandro
author_facet Rajasekharan, Sreejith
Milan Bonotto, Rafaela
Nascimento Alves, Lais
Kazungu, Yvette
Poggianella, Monica
Martinez-Orellana, Pamela
Skoko, Natasa
Polez, Sulena
Marcello, Alessandro
author_sort Rajasekharan, Sreejith
collection PubMed
description Repurposing clinically available drugs to treat the new coronavirus disease 2019 (COVID-19) is an urgent need in the course of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) pandemic, as very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases, such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated in the micromolar range for SARS-CoV-2 in vitro. The drug acts at the post-entry level and leads to a marked decrease of viral proteins and release of infectious viruses. The mechanism resides in the inhibitory activity toward α-glucosidases that are involved in the early stages of glycoprotein N-linked oligosaccharide processing in the endoplasmic reticulum, leading to a marked decrease of the viral Spike protein. Indeed, the antiviral potential of protein glycosylation inhibitors against SARS-CoV-2 is further highlighted by the low-micromolar activity of the investigational drug Celgosivir. These data point to a relevant role of this approach for the treatment of COVID-19.
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spelling pubmed-81449692021-05-26 Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2 Rajasekharan, Sreejith Milan Bonotto, Rafaela Nascimento Alves, Lais Kazungu, Yvette Poggianella, Monica Martinez-Orellana, Pamela Skoko, Natasa Polez, Sulena Marcello, Alessandro Viruses Article Repurposing clinically available drugs to treat the new coronavirus disease 2019 (COVID-19) is an urgent need in the course of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) pandemic, as very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases, such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated in the micromolar range for SARS-CoV-2 in vitro. The drug acts at the post-entry level and leads to a marked decrease of viral proteins and release of infectious viruses. The mechanism resides in the inhibitory activity toward α-glucosidases that are involved in the early stages of glycoprotein N-linked oligosaccharide processing in the endoplasmic reticulum, leading to a marked decrease of the viral Spike protein. Indeed, the antiviral potential of protein glycosylation inhibitors against SARS-CoV-2 is further highlighted by the low-micromolar activity of the investigational drug Celgosivir. These data point to a relevant role of this approach for the treatment of COVID-19. MDPI 2021-04-30 /pmc/articles/PMC8144969/ /pubmed/33946304 http://dx.doi.org/10.3390/v13050808 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rajasekharan, Sreejith
Milan Bonotto, Rafaela
Nascimento Alves, Lais
Kazungu, Yvette
Poggianella, Monica
Martinez-Orellana, Pamela
Skoko, Natasa
Polez, Sulena
Marcello, Alessandro
Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2
title Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2
title_full Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2
title_fullStr Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2
title_full_unstemmed Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2
title_short Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2
title_sort inhibitors of protein glycosylation are active against the coronavirus severe acute respiratory syndrome coronavirus sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144969/
https://www.ncbi.nlm.nih.gov/pubmed/33946304
http://dx.doi.org/10.3390/v13050808
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