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. 2021 Jan 10;31(5):e2213. doi: 10.1002/rmv.2213

FIGURE 4.

FIGURE 4

Proposed detrimental role of sACE2 in SARS‐CoV‐2 entry and subsequent disease severity in site of infection and distant cells: (a) in sACE2 abundant condition, virus S protein may partially be covered with circulatory sACE2 forming virus–sACE2 complex and can be primed by floating serine proteases; (b) it can enter its genetic material by membrane fusion; (c) few available mACE2 can bind the virus–sACE2 complex and endocytosis can proceed through several mechanisms; (d) virus–sACE2 complex can be internalized by receptor‐independent macropinocytosis; and (e) the complex can travel to distant cell where serine protease activity is low or absent. In all internalization processes, the virus–sACE2 complex takes sACE2 inside creating rapid crisis of sACE2 and increase of Ang II. This may lead to RAS imbalance and COVID‐19 severity. Ang II, angiotensin II; COVID‐19¸ coronavirus disease 2019; mACE2, membrane ACE2; sACE2, soluble ACE2; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2