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. Graphical abstract Image 1 Significance: « short abstract » Covid-19 treatment could benefit from repurposing strategies for already used drugs, allowing a rapid clinical development. SARS-CoV-2 virus enters its target cells by interacting with their plasma membrane receptor, ACE2, localized in raft-type cholesterol-enriched lipid domains. It is here proposed to take benefit from the well-documented anti-cholesterol effect of the statin family, which would allow to disorganize these cholesterol-enriched membrane microdomains. Statins are widely-used safe drugs for long-term prevention of cardiovascular risk, thus presenting a high efficiency-to-toxicity ratio. This new therapeutic, host-targeted approach has the further advantage to avoid any drug resistance due to possible virus mutations.
【저자키워드】 COVID-19, Drug repurposing, coronavirus, cholesterol, statins, Membrane microdomains,