Binding of SARS-CoV-2 with its cellular receptor, ACE2, results in loss of ACE2 and its cardioprotective effects. The entry of SARS-CoV-2 into the cell is facilitated by TMPRSS2 that primes S-protein. Virus may also enter through endocytosis and become activated by cathepsin L, although other proteases such as furin may also activate SARS-CoV-2. Following virus entry into host cells, SARS-CoV-2 undergoes RNA replication within endosomes. ADAM17 (a disintegrin and metalloproteinase 17) activity is up-regulated by the endocytosed S-proteins of SARS-CoV, and though not proven, likely to be by SARS-CoV-2 given the similarity of viral interactions with ACE2. ADAM17 mediates the proteolytic cleavage of ACE2, releasing soluble ACE2 (sACE2) into the circulation.