ABSTRACT
There are no effective therapies for COVID-19 or antivirals against SARS-CoV-2. Furthermore, current vaccines appear less efficacious for new SARS-CoV-2 variants. Thus, there is an urgent need to better understand the virulence mechanisms of SARS-CoV-2 and the host response to develop therapeutic agents. Here, we show host Neu1 regulates coronavirus replication by controlling sialylation on coronavirus nucleocapsid protein. Coronavirus nucleocapsid proteins in COVID-19 patients and in coronavirus HCoV-OC43-infected cells were heavily sialylated; this sialylation controlled the RNA binding activity and replication of coronavirus. Neu1 overexpression increased HCoV-OC43 replication, whereas Neu1 knockdown reduced HCoV-OC43 replication. Moreover, a newly developed Neu1 inhibitor, Neu5Ac2en-OAcOMe, selectively targeted intracellular sialidase, which dramatically reduced HCoV-OC43 and SARS-CoV-2 replication in vitro and rescued mice from HCoV-OC43 infection-induced death. Our findings suggest that Neu1 inhibitors could be used to limit SARS-CoV-2 replication in patients with COVID-19, making Neu1 a potential therapeutic target for COVID-19 and future coronavirus pandemics.
ABSTRACT
Objective To study MR imaging features of dysembryoplastic neuroepithelial tumors (DNET). Methods MRI ap-pearances of 10 patients with surgery and pathology proved DNET were analyzed retrospectively. All of 10 patients underwent routine and contrast-enhanced MRI. Results All lesions were located in the regions near the surface of brain,including frontal lobe (4 ca-ses) ,parietal lobe (4 cases),temporal lobe (1 case) and parietoinsular lobe (1 case). The lesions appeared as sector in 4 cases, re-versed triangle in 4 cases,irregularity in 2 cases. Homogeneous or heterogeneous long T_1 and long Tz signal intensity were seen on MR imaging. The lesion showed predominant cystic component and septa, no obvious mass effect and peritumoral edema could be found in all cases. Bone thinning of the adjacent calvaria could be seen in 6 cases. On post contrast MRI scan,the lesions had no obvi-ous enhancement in 6 cases ,while mild enhancement could be found in the intra-tumorous solid nodule or septations in 4 cases. Conclusion DNETs are of certain clinical manifestations and MRI features,it is helpful for preoperative diagnosis of DNET.