Coronavirus disease 2019 , caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism.Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.

P reeclampsia (PE), affecting ≈5% to 7% of pregnancies worldwide, is a multisystem syndrome that occurs during the third trimester of human pregnancy, and it is a leading cause of maternal and perinatal morbidity and mortality. [1][2][3][4] Placental deficiencies are widely recognized as the principal pathological origin of the disorder.Preeclamptic patients usually present with high circulating testosterone and reduced estradiol production during gestation, and therefore, they are considered to experience endocrine disorders. [5][6][7][8] Physiologically, the circulating testosterone and estradiol levels in pregnant women increase from the first trimester and are further elevated toward the end of pregnancy. 9 The placenta is an important source of steroid hormone production throughout gestation, although the ovarian luteal cells have that role in early pregnancy. The placenta can manufacture pregnenolone and express several enzymes that are fundamentally required for the biosynthetic conversion of cholesterol to androgens and estrogens, such as CYP17 (17α-hydroxy/17,20-lyase), 3β-HSD (3β-hydroxysteroid dehydrogenase), 17β-HSD, and aromatase. Specifically, the placental aromatase acts to convert androstenedione (A 4 ) into estrone (E 1 ), and testosterone (T 0 ) into 17β-estradiol (E 2 ), and 17β-HSD3 works to convert A 4 into T 0 .9 The aberrantly increased testosterone level and decreased estradiol Abstract-Preeclampsia, a multisystem syndrome occurring during mid-to late gestation in humans, is a leading cause of maternal and perinatal morbidity and mortality. Patients usually present with high circulating testosterone and reduced estradiol production, but the mechanisms remain unclear. Revealing the mechanism that modulating the imbalance of testosterone and estradiol in preeclampsia is of great value in understanding the cause of the disease. The placenta is the predominant source of steroid hormone production during gestation, and we observed markedly increased 17β-HSD3 (17β-hydroxysteroid dehydrogenase 3) levels and downregulated aromatase expression, the key enzymes responsible for synthesis of testosterone and estradiol, respectively, in preeclamptic placentas compared with controls. Furthermore, we found a significant upregulation of microRNA (miR)-22 in preeclamptic placentas. In a trophoblast cell line, JEG-3 cells, testosterone repressed the expression of aromatase and estrogen receptor α and the production of estradiol while promoting miR-22 expression. miR-22 directly targeted and inhibited estrogen receptor α expression while indirectly decreasing aromatase expression and estradiol production by interfering with estrogen receptor α signaling. Furthermore, inhibition of miR-22 expression significantly reversed the inhibitory effect of testosterone on de novo estradiol synthesis in human trophoblastic cells. The findings reveal a mechanism underlying the balanced production of androgen and estrogen modulated by miR-22 in the human placenta and provide new insights into the pathogenesis of preeclam...