Fig. 4.

Illustration of SARS-CoV-2–host–statin interactions. The center (‘nuclear’ blue area) shows the relationships among virus and epigenetic modifications (left) and aspects of the host immune response in response to the epigenetic changes (right). The upper right is a lipid raft (maroon) with contents regulated by statins and pleiotropic effects linked to isoprenoid group deficiency. ACE2 receptor gains function. Suppression of inflammatory and thrombotic mediators by statins, directly and indirectly, modifies the level of inflammation and other COVID-19-induced responses, that is, the ‘cytokine storm’. Following left underneath under the nuclear area, the vasoprotective actions of statins drugs include normalization of nitric oxide production and endothelial function. ACE2, angiotensin-converting enzyme 2; COX2, cyclooxygenase2; cPLA2, c-phospholipase; ET, endothelin; FPP, Farnesyl pyrophosphate; IL, interleukin; MHC, major histocompatibility; MPro, main protease; MYD88, myeloid differentiation factor; NOS, nitric oxide synthase; PAI-1, plasminogen activator inhibitor; RdRp, RNA-dependent RNA polymerase; TF, tissue factor; TM, thrombomodulin; TNF, tumor necrosis factor; TXA2, thromboxane.