Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

PubMed Disclaimer

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.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res 176: 104742, 2020. doi:10.1016/j.antiviral.2020.104742. - DOI - PMC - PubMed
    1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19 . Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med In press. doi:10.1056/NEJMoa2002032. - DOI - PMC - PubMed
    1. Hallenberger S, Bosch V, Angliker H, Shaw E, Klenk HD, Garten W. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature 360: 358–361, 1992. doi:10.1038/360358a0. - DOI - PubMed
    1. Hosaka M, Nagahama M, Kim WS, Watanabe T, Hatsuzawa K, Ikemizu J, Murakami K, Nakayama K. Arg-X-Lys/Arg-Arg motif as a signal for precursor cleavage catalyzed by furin within the constitutive secretory pathway. J Biol Chem 266: 12127–12130, 1991. - PubMed
    1. Ichiki T, Burnett JC Jr. Post-transcriptional modification of pro-BNP in heart failure: is glycosylation and circulating furin key for cardiovascular homeostasis? Eur Heart J 35: 3001–3003, 2014. doi:10.1093/eurheartj/ehu381. - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources