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Comment
. 2020 May 19;52(5):731-733.
doi: 10.1016/j.immuni.2020.04.003. Epub 2020 Apr 22.

COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome

Toshio Hirano  1 , Masaaki Murakami  2
Affiliations
Comment

COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome

Toshio Hirano et al. Immunity. .

Abstract

Zhou et al. (Nature) and Hoffmann et al. (Cell) identify ACE2 as a SARS-CoV-2 receptor, and the latter show its entry mechanism depends on cellular serine protease TMPRSS2. These results may explain proinflammatory cytokine release via the associated angiotestin II pathway and a possible therapeutic target via the IL-6-STAT3 axis.

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Figures

Figure 1
Figure 1
Possible therapeutic targets for COVID-19, a cytokine release syndrome. SARS-CoV-2 uses angiotensin converting enzyme II (ACE2) and transmembrane serine protease 2 (TMPRSS2) as cell entry receptors, followed by a cytokine-related syndrome, ARDS, which is induced by the hyper-activation of the transcription factor NF-κB, most likely in nonimmune cells including lung epithelial cells. ACE2 molecules on the cell surface are occupied by SARS-CoV-2. Angiotensin 2 (AngII) then increases in the serum due to a reduction of ACE2-mediated degradation. SARS-CoV-2 itself activates NF-κB via pattern recognition receptors (PPRs), and the accumulated AngII induces inflammatory cytokines including TNFα and IL-6-soluble (s)IL-6R via disintegrin and metalloprotease 17 (ADAM17), followed by activation of the IL-6 amplifier (IL-6 AMP), which describes enhanced NF-κB activation machinery via the coactivation of NF-κB and transcription factor STAT3. The molecules underlined indicate possible therapeutic targets for COVID-19, which is a cytokine release syndrome (CRS).
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