Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry

Published: July 29, 2020, 5:01 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.29.227249v1?rss=1 Authors: Aguilar Pineda, J., Albaghdadi, M., Jiang, W., Vera Lopez, K. J., Lindsay, M. E., Davila del-Carpio, G., Gomez Valdez, B., Malhotra, R., Lino Cardenas, C. L. Abstract: Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further observed that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV2 thereby blocking its entry into cells. In a mouse model, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19. Copy rights belong to original authors. Visit the link for more info