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. 2020 May 1;318(5):L1020-L1022.
doi: 10.1152/ajplung.00097.2020. Epub 2020 Mar 24.

Covid-19 infection and mortality: a physiologist's perspective enlightening clinical features and plausible interventional strategies

Zaid A Abassi  1   2 , Karl Skorecki  3 , Samuel Noam Heyman  4 , Safa Kinaneh  1 , Zaher Armaly  3   5
Affiliations

Covid-19 infection and mortality: a physiologist's perspective enlightening clinical features and plausible interventional strategies

Zaid A Abassi et al. Am J Physiol Lung Cell Mol Physiol. .
No abstract available

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1.
Fig. 1.
The initial step after the invasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is binding to membranal angiotensin-converting enzyme 2 receptor (ACE2), widely expressed in various organs, including, lungs, heart, kidney, intestinal, vascular endothelium, and testis. This step is preceded by furin-mediated exposure of the viral receptor binding protein (RBP) localized to S-glycoprotein (S1 domain of the viral spike). Furin is expressed in various target organs, including the heart, but is also present in the circulation as a free enzyme, making it a key factor in the uncovering of RBP and eventually in SARS-CoV-2 transmission. Moreover, circulating and intracellular furin enhances the affinity of the virus to ACE2, not only by exposing the viral binding site on S1 domain but also by revealing the effusion site on the S2 domain in the viral spike. Consequently, the virus undergoes endocytosis, interaction with lysosomal Cathepsin L and massive replication accompanied by profound activation by the abundant intracellular furin. The activated intracellular SARS-CoV-2 undergoes exocytosis, where it binds again to ACE2 elsewhere, thus creating a vicious feed-forward, devastating cycle. This may explain the nonremitting clinical presentation in critically ill SARS-CoV-2-infected patients. Importantly, drugs that upregulate ACE2, such as angiotensin-II inhibitors (ACE-I), angiotensin receptor blockers (ARBs), and mineralocorticoid receptor (MR) antagonists, sensitize ACE2-expressing target organs to SARS-CoV-2. ADAM17, A disintegrin and metalloproteinase 17; COX, cyclooxygenase; ER, endoplasmic reticulum; TMPRSS2, type II transmembrane serine protease.
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References

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