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Coronaviruses, cholesterol and statins: Involvement and application for Covid-19

The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorgani...

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Autores principales: Orlowski, Stéphane, Mourad, Jean-Jacques, Gallo, Antonio, Bruckert, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. Published by Elsevier B.V. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213520/
https://www.ncbi.nlm.nih.gov/pubmed/34153377
http://dx.doi.org/10.1016/j.biochi.2021.06.005
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author Orlowski, Stéphane
Mourad, Jean-Jacques
Gallo, Antonio
Bruckert, Eric
author_facet Orlowski, Stéphane
Mourad, Jean-Jacques
Gallo, Antonio
Bruckert, Eric
author_sort Orlowski, Stéphane
collection PubMed
description The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. As a consequence, numerous cell physiology processes, such as signaling cascades, can be compromised. Also, some examples of anti-bacterial and anti-viral effects of statins have been observed for infectious agents known to be cholesterol dependent. In-vivo, besides their widely-reported hypocholesterolemic effect, statins display various pleiotropic effects mediated, at least partially, by perturbation of membrane microdomains as a consequence of the alteration of endogenous cholesterol synthesis. It should thus be worth considering a high, but clinically well-tolerated, dose of statin to treat Covid-19 patients, in the early phase of infection, to inhibit virus entry into the target cells, in order to control the viral charge and hence avoid severe clinical complications. Based on its efficacy and favorable biodisposition, an option would be considering Atorvastatin, but randomized controlled clinical trials are required to test this hypothesis. This new therapeutic proposal takes benefit from being a drug repurposing, applied to a widely-used drug presenting a high efficiency-to-toxicity ratio. Additionally, this therapeutic strategy avoids any risk of drug resistance by viral mutation since it is host-targeted. Noteworthy, the same pharmacological approach could also be proposed to address different animal coronavirus endemic infections that are responsible for heavy economic losses.
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spelling pubmed-82135202021-06-21 Coronaviruses, cholesterol and statins: Involvement and application for Covid-19 Orlowski, Stéphane Mourad, Jean-Jacques Gallo, Antonio Bruckert, Eric Biochimie Article The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. As a consequence, numerous cell physiology processes, such as signaling cascades, can be compromised. Also, some examples of anti-bacterial and anti-viral effects of statins have been observed for infectious agents known to be cholesterol dependent. In-vivo, besides their widely-reported hypocholesterolemic effect, statins display various pleiotropic effects mediated, at least partially, by perturbation of membrane microdomains as a consequence of the alteration of endogenous cholesterol synthesis. It should thus be worth considering a high, but clinically well-tolerated, dose of statin to treat Covid-19 patients, in the early phase of infection, to inhibit virus entry into the target cells, in order to control the viral charge and hence avoid severe clinical complications. Based on its efficacy and favorable biodisposition, an option would be considering Atorvastatin, but randomized controlled clinical trials are required to test this hypothesis. This new therapeutic proposal takes benefit from being a drug repurposing, applied to a widely-used drug presenting a high efficiency-to-toxicity ratio. Additionally, this therapeutic strategy avoids any risk of drug resistance by viral mutation since it is host-targeted. Noteworthy, the same pharmacological approach could also be proposed to address different animal coronavirus endemic infections that are responsible for heavy economic losses. The Authors. Published by Elsevier B.V. 2021-10 2021-06-18 /pmc/articles/PMC8213520/ /pubmed/34153377 http://dx.doi.org/10.1016/j.biochi.2021.06.005 Text en © 2021 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Orlowski, Stéphane
Mourad, Jean-Jacques
Gallo, Antonio
Bruckert, Eric
Coronaviruses, cholesterol and statins: Involvement and application for Covid-19
title Coronaviruses, cholesterol and statins: Involvement and application for Covid-19
title_full Coronaviruses, cholesterol and statins: Involvement and application for Covid-19
title_fullStr Coronaviruses, cholesterol and statins: Involvement and application for Covid-19
title_full_unstemmed Coronaviruses, cholesterol and statins: Involvement and application for Covid-19
title_short Coronaviruses, cholesterol and statins: Involvement and application for Covid-19
title_sort coronaviruses, cholesterol and statins: involvement and application for covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213520/
https://www.ncbi.nlm.nih.gov/pubmed/34153377
http://dx.doi.org/10.1016/j.biochi.2021.06.005
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