Abstract
ABSTRACTEbola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013–2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infection in vitro. Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7. Statin treatment did not interfere with viral entry, but the viral particles released from treated cells showed reduced infectivity due to inhibition of viral glycoprotein processing, as evidenced by decreased ratios of the mature glycoprotein form to precursor form. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Finally, statin-treated cells produced EBOV particles devoid of the surface glycoproteins required for virus infectivity. Our findings demonstrate that statin treatment inhibits EBOV infection and suggest that the efficacy of statin treatment should be evaluated in appropriate animal models of EVD.
Highlights
Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments
To test if statins affect EBOV replication, Huh7 cells were infected with the EBOV variant Mayinga (Ebola virus/H. sapiens-tc/ COD/1976/Yambuku-Mayinga) at a multiplicity of infection (MOI) of 0.05
After 1 h of virus adsorption, the cells were treated with dimethyl sulfoxide (DMSO) or with 20 M or 50 M lovastatin, the first clinically approved statin, in medium supplemented with lipoproteindeficient serum (LPDS)
Summary
Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Widely used cholesterollowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013–2016 outbreak in West Africa. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Statins are already FDA approved for reducing high cholesterol, have a favorable safety profile, and are inexpensive. They were suggested as a possible adjunct therapy for EVD patients during the 2013–2016 outbreak [10]. Cholesterol-dependent interactions between EBOV glycoproteins (GPs) are essential for virus assembly [15] This further suggests that drugs lowering cholesterol levels, like statins, could be useful therapeutics for EVD patients
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