Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2

The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social and economic stability. In this study, we established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus S protein and its host receptor ACE2. This platform is a rapid, sensitive, specific, and high throughput system. With this platform, we screened two compound libraries of 2,864 molecules and identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S-protein and the human cell ACE2 receptor. This data suggests that TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug. SIGNIFICANCEThe ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. In this present study, we screened two compound libraries of 2,864 molecules and identified a potent inhibitor (TS-984) for blocking the coronavirus S-protein and the human cell ACE2 receptor. TS-984 might have the potential to be developed into an effective anti-coronavirus drug for treating COVID-19.

The applied research of ultrasound-guided percutaneous thrombin injection for the treatment of Iarogenic femoral arterial complexity pseudoaneurysms / 重庆医学

Objective The aim to assess the methodology and feasibility of ultrasound guided percutaneous thrombin injection(UGTI) for the treatment of Iarogenic Femoral Arterial Complexity Pseudoaneurysms(IFACP).Methods Thirty two iarogenic femoral arterial complexity pseudoaneurysms patients following femoral arerial puncture for arterial angiography were treated with UGTI.Twenty-three IFACP with 2 lobes,8 IFACP with 3 lobes,1 IFACP with 4 lobes.Under local anesthesia the lobe was pene trated by artery needle successively and thrombin jection was performed slowely into distal lobe with US guide precise localization.Dynamical observation was performed for the status of thrombogenesis and cavity plugging.US follow-up examination were performed after 24 h and 7 d.Results Reperfusion occurred in IFACP with 3 lobes after 24 h and UGTI failure.IFACPs with 4 lobes failure.Nothromboembolic,infectious,allergic complication soccurred.Conclusion UGTI is the first mothed for the treatment of IFACP.Precise localization and percutaneous can enhance the ratio of treatment of IFACPs and avoid the severe complications.

Insights into the clinical value of cyclin-dependent kinase 5 in glioma: a retrospective study.

BACKGROUND: Previous studies suggested that expression of cyclin-dependent kinase 5 (CDK5) may promote the migration and invasion of human glioma cells. In this study, we aimed to evaluate the clinical value of CDK5 in different grades of glioma in relation to Ki-67 labeling index (LI). METHODS: We firstly assessed by immunohistochemistry the expression of CDK5 in 152 glioma tissues and 16 normal brain tissues and further explored the relationship between CDK5 expression and other clinical features. RESULTS: The positive ratio of CDK5 in gliomas (57.2%) was higher than that in normal brain tissues (12.5%, P=0.001). Difference of CDK5 expression among four World Health Organization (WHO) grades was statistically significant (P=0.001). The significant differences of CDK5 expression were also observed between WHO I glioma (34.8%) and WHO III glioma (62.5%), as well as WHO IV glioma (82.8%; P=0.026, P<0.001, respectively). Furthermore, Spearman's rank correlation confirmed that CDK5 was positively correlated with the pathological grade of glioma (r=0.831, P<0.001). The CDK5 expression was also positively correlated with Ki-67 LI (r=0.347, P<0.001). CONCLUSIONS: The current result suggests that CDK5 may play an essential role in the tumorigenesis and aggressiveness of gliomas.

Analysis and research on spectrum signal of mice blood based on hilbert-huang transform / 中国医学装备

Objective:To provide a criterion for determining whether a mouse's health by analyzing the time-frequency local characteristics of nonlinear and unsteady mice blood spectrum signal.Methods: Collect the blood spectrum signal of the normal and liver damage mice by infrared spectrum method, then study the mice blood spectrum signal by Hilbert - huang transform method.Results: Initially formed criterion on judge whether there is hepatic injury in mice signal.Conclusion: Analysis method based on HHT in mice blood signal spectrum analysis can accurately determine the health of the mice and it provides a new method of analysis for noninvasive blood tests.

MR features of mice spleen lymphocytes labeled with super-paramagnetic iron oxide particles / 中华放射学杂志

Objective To investigate the feasibility of labeling mice spleen lymphocytes with superparamagnetic iron oxide(SPIO)and in vitro MR imaging of the labeled cells.Methods Spleen lymphocytes of 5 mice were isolated and then labeled with SPIO of 100,50,25,15,10,5 μg/ml,which was previously prepared with PLL.Prussian blue staining was performed to show the intracellular iron.Cell viability was compared among fresh,labeled and unlabeled cells.Different concentrations of mice spleen lymphocytes were screened using 3.0 T MR on T2WI,T2 * WI and SWI sequences in vitro.Cell viability was compared using independent-sample t test between groups.The MRI values among different groups were compared using one-way ANOVA.Results SPIO prepared with PLL could successfully label mice spleen lymphocytes,the optimum concentration of SPIO was 5 μg/ml.The Prussian blue staining showed intracellular blue spots and a labeling efficiency of(93.6 ± 2.1)％.Three groups of fresh,labeled and unlabeled cells showed a Trypan blue staining result of(94.8 ± 3.1)％,(88.7 ± 2.7)％,and(88.9 ±3.2)％,respectively; no statistically significant difference was found in cell viability between labeled and unlabeled lymphocytes(t =0.281,P ＞ 0.05); however,the cell viability of fresh cells were statistically significant higher than the labeled and unlabeled lymphocytes(t =8.125 and 7.253 respectively,P ＜0.05for all).Among the T2 WI,T2 * WI and SWI sequences under the same concentrations of cells,the SWI sequence was the most sensitive.Conclusions The mice spleen lymphocytes can be effectively labeled with SPIO with no impact on cell viability,and MR can be used to track these labeled cells in vitro.The SWI sequence is the most sensitive.