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. 2020 Jun 19;11:1472. doi: 10.3389/fimmu.2020.01472

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Copyright © 2020 Sfera, Osorio, Jafri, Diaz and Campo Maldonado.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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TMPRSS2 and ADAM17 are two virus-usurped host proteases. The former primes the spike (S) protein into S1, the active receptor binding site, promoting viral ingress. The latter, ADAM17, sheds the ACE-2 ectodomain, downregulating these proteins. The shed virus-ACE-2 complexes are soluble and readily spread by the circulation, causing end-organ damage, and critical illness. Some protease inhibitors may downregulate both TMPRSS2 and ADAM17, providing added therapeutic benefit for COVID-19 patients.