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

Abstract

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.

Keywords: Cholesterol; Coronavirus; Covid-19; Drug repurposing; Membrane microdomains; Statins.

Graphical abstract

Scheme 1

The « take-home message » Overview of the different underlying biological data supporting the proposed repurposing strategy for statins against SARS-CoV-2 infection. Note that in-vitro and in-vivo (preclinical and clinical) situations for statin effects both can occur in the sub-micromolar concentration range.

Scheme 2

« Graphical abstract » Simplified cartoon describing the mechanism of action underlying the proposed repurposing of statins for fighting against Covid-19 by inhibiting SARS-CoV-2 entry into the target cells.