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 report 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-CoV-2 thereby blocking its entry into cells. In a mouse model of COVID-19, 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.
【저자키워드】 COVID-19, ACE2, Sex hormones, estrogenes, 【초록키워드】 SARS-CoV-2, Severe infection, therapy, glycosylation, Estrogen, ACE2 receptor, Spike protein, human ACE2, Protein, cells, male, female, mechanism, Evidence, Interaction, sex hormone, molecular basis, human ACE2 receptor, alveolar, females, susceptible, ENhance, reduced, variety, disrupt, underlie, the SARS-CoV-2, the SARS-CoV-2 virus, 【제목키워드】 SARS-CoV-2, hormone,