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SARS-CoV2 S Protein Features Potential Estrogen Binding Site

Ante Tomasović*orcid tiny, Damir Stanzerorcid tiny, Ivan Krešimir Svetecorcid tiny and Marina Svetec Miklenić*orcid tiny

Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia


Article history:

Received: 27 May 2020

Accepted: 8 February 2021

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Key words:

SARS-CoV2, coronavirus, S protein, estrogen, estradiol, estrogen binding site


Research background. During the current SARS-CoV2 pandemic, as well as earlier SARS and MERS epidemics, it has been observed that COVID19-positive women on average tend to have milder symptoms and lower fatality rates than men. There is a number of differences between the sexes known to contribute to different immune responses and severity of the disease, one being the effect of estrogen via estrogen receptor signalling. We wondered if estrogen might also affect the SARS-CoV2 more directly, perhaps by binding to the surface glycoprotein (S protein), thus possibly reducing its infectivity.

Experimental approachTo assess whether there is a possibility for estrogen binding on the SARS-CoV2 S protein we used BLAST and HHpred to compare protein sequences of S protein and human estrogen receptor β, while 3D structures of a potential estrogen binding site and an active site of estrogen receptor β were visualized and compared using PyMOL. 

Results and conclusionsBy comparing the protein sequence of SARS-CoV2 S protein with the human estrogen receptor β, we identified a potential estrogen binding site on S protein and further determined that it also shares notable similarities with the active site of ER β when observed in 3D structure of their respective proteins. As a control, SARS-CoV2 S protein was compared with the human androgen receptor, and no such similarities were found. The potential estrogen binding site is part of coronavirus S2 superfamily domain, which is involved in host-virus membrane fusion during infection and appears to be conserved throughout the Coronaviridae family.

Novelty and scientific contributionThis preliminary communication shows that SARS-CoV2 S protein features a potential estrogen binding site. Hopefully, this will prompt a more comprehensive study on the possibilities of estrogen binding on the S protein and the effect this might confer on the virus infectivity.

*Corresponding author:

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