25-hydroxy Cholesterol is an oxysterol.
1 It is formed from cholesterol by cholesterol-25-hydroxylase, and its production can be induced by inflammation or infection.
2 25-hydroxy Cholesterol suppresses endogenous cholesterol synthesis by binding to insulin-induced gene (INSIG) proteins and preventing sterol regulatory element binding proteins (SREBPs) from being transported to the Golgi. It inhibits IgA class switching induced by LPS and various cytokines in B cells (IC
50 = ~50 nM).
3 25-hydroxy Cholesterol inhibits replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Vero cells (EC
50 = 3.675 μM) and reduces increases in viral protein production in infected Vero cells when used prior to infection.
4 It reduces viral RNA loads in the lung and trachea in a mouse model of SARS-CoV-2 infection when administered at a dose of 100 mg/kg per day. Serum levels of 25-hydroxy cholesterol are increased in mice expressing human angiotensin-converting enzyme 2 (hACE2), the functional receptor for SARS-CoV-2, in a model of SARS-CoV-2 infection and in a patient with COVID-19, the primarily respiratory disease caused by SARS-CoV-2.