The potential role of scavenger receptor B type I (SR‐BI) in SARS‐CoV‐2 infection

Abstract

Scavenger receptor type B I (SR-BI), the major receptor for high-density lipoprotein (HDL) mediates the delivery of cholesterol ester and cholesterol from HDL to the cell membrane. SR-BI is implicated as a receptor for entry of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). SR-BI is colocalized with the angiotensin-converting enzyme 2 (ACE2) increasing the binding and affinity of SARS-CoV-2 to ACE2 with subsequent viral internalization. SR-BI regulates lymphocyte proliferation and the release of pro-inflammatory cytokines from activated macrophages and lymphocytes. SR-BI is reduced during COVID-19 due to consumption by SARS-CoV-2 infection. COVID-19-associated inflammatory changes and high angiotensin II (AngII) might be possible causes of repression of SR-BI in SARS-CoV-2 infection. In conclusion, the downregulation of SR-BI in COVID-19 could be due to direct invasion by SARS-CoV-2 or through upregulation of proinflammatory cytokines, inflammatory signaling pathways, and high circulating AngII. Reduction of SR-BI in COVID-19 look like ACE2 may provoke COVID-19 severity through exaggeration of the immune response. Further studies are invoked to clarify the potential role of SR-BI in the pathogenesis of COVID-19 that could be protective rather than detrimental.

SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway

“…SARS-CoV-2 infection primarily affects the vascular endothelium leading to endothelial dysfunction and the development of coagulopathy (Alrouji et al 2023b ; Alkazmi et al 2023b ; Alomair et al 2023 ). SARS-CoV-2 infects the endothelial cells directly due to the abundance expression of ACE2, causing cellular injury and apoptosis with subsequent reduction of endothelial cells’ capacity to release anti-thrombotic factors (Alomair et al 2023 ).…”