4.7 Article

AGTR2, One Possible Novel Key Gene for the Entry of SARS-CoV-2 Into Human Cells

Publisher

IEEE COMPUTER SOC
DOI: 10.1109/TCBB.2020.3009099

Keywords

Proteins; Lung; Receptor (biochemistry); Databases; Gene expression; Compounds; Viruses (medical); SARS-CoV-2; receptor; ACE2; AGTR2

Funding

  1. Basic research program of Peking University [BMU2020JC001]

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Recent research has found that AGTR2, which interacts with ACE2 and is highly expressed in the lungs, may play a key role in the entry of SARS-CoV-2 into human cells. This suggests a potential novel gene involved in the infection process and could provide new insights for future research.
Recently, it was confirmed that ACE2 is the receptor of SARS-CoV-2, the pathogen causing the recent outbreak of severe pneumonia around the world. It is confused that ACE2 is widely expressed across a variety of organs and is expressed moderately but not highly in lung, which, however, is the major infected organ. Therefore, we hypothesized that there could be some other genes playing key roles in the entry of SARS-CoV-2 into human cells. Here we found that AGTR2 (angiotensin II receptor type 2), a G-protein coupled receptor, has interaction with ACE2 and is highly expressed in lung with a high tissue specificity. More importantly, simulation of 3D structure based protein-protein interaction reveals that AGTR2 shows a higher binding affinity with the Spike protein of SARS-CoV-2 than ACE2 (energy: -8.2 vs. -5.1 [kcal/mol]). A number of compounds, biologics and traditional Chinese medicine that could decrease the expression level of AGTR2 were predicted. Finally, we suggest that AGTR2 could be a putative novel gene for the entry of SARS-CoV-2 into human cells, which could provide different insight for the research of SARS-CoV-2 proteins with their receptors.

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