New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective To analyze the clinical features of medullary thyroid carcinoma(MTC) and the risk factors of cervical lymph node metastasis.Methods A retrospective analysis of 84 cases of thyroid surgery in the First Affiliated Hospital of Zhengzhou University from Jan.2012 to Jun.2018 and confirmed by routine pathology as MTC patients was performed.Chi-square test and logistic regression were used to analyze patients' age,gender,clinical features such as tumor diameter,number of lesions,and invasion of the capsule and risk factors associated with cervical lymph node metastasis.Results Statistical analysis found that the incidence of lymph node metastasis significantly increased in patients with central region ≥ 1 cm (x2=4.196,P=0.041),multiple lesions (x2=5.946,P=0.015),and thyroid capsule invasion (x2=15.277,P＜0.001) and the difference was statistically significant.The incidence of cervical lymph node metastasis was significantly higher in patients with the tumor diameter ≥ 1 cm(x2=5.269,P=0.022),multiple lesions(x2=4.550,P=0.033),and thyroid capsule invasion(x2=19.253,P＜0.001) and the difference was statistically significant.Logistic regression analysis showed that thyroid capsule invasion was an independent risk factor for central lymph node metastasis (OR=7.551,P=0.001) and cervical lymph node metastasis (OR=8.067,P＜0.001).Of the 84 patients who received calcitonin before surgery,56 patients had preoperative calcitonin＞200 pg/ml,and the cervical lymph node metastasis rate was 55.4％ (31/56).28 patients had preoperative calcitonin＜200 pg/ml,and the cervical lymph node metastasis rate was 28.6％ (8/28).The former increased and the difference was statistically significant.Of the 18 patients who underwent preoperative detection of carcinoembryonic antigen (CEA),8 patients had CEA＞30 ng/ml,cervical lymph node metastasis was 75％ (6/8);10 patients had CEA＜30 ng/ml,and the cervical lymph node metastasis was 60％(6/10).Conclusions Higher cervical lymph node metastasis is a clinical feature of MTC.For patients with thyroid capsule invasion,the risk of cervical lymph node metastasis is significantly increased,and prophylactic cervical lymph node dissection is required.Preoperative detection of calcitonin and CEA can be used to diagnose MTC and predict lymph node metastasis.The cervical lymph node dissection can be considered with reference to the concentration.