Allosteric binders of ACE2 are promising anti-SARS-CoV-2 agents

The COVID-19 pandemic has had enormous health, economic, and social consequences. Vaccines have been successful in reducing rates of infection and hospitalization, but there is still a need for an acute treatment for the disease. We investigate whether compounds that bind the human ACE2 protein can interrupt SARS-CoV-2 replication without damaging ACE2s natural enzymatic function. Initial compounds were screened for binding to ACE2 but little interruption of ACE2 enzymatic activity. This set of compounds was extended by application of quantitative structure-activity analysis, which resulted in 512 virtual hits for further confirmatory screening. A subsequent SARS-CoV-2 replication assay revealed that five of these compounds inhibit SARS-CoV-2 replication in human cells. Further effort is required to completely determine the antiviral mechanism of these compounds, but they serve as a strong starting point for both development of acute treatments for COVID-19 and research into the mechanism of infection. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/484484v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@173d7c9org.highwire.dtl.DTLVardef@5c0021org.highwire.dtl.DTLVardef@c9caaorg.highwire.dtl.DTLVardef@18d23_HPS_FORMAT_FIGEXP M_FIG TOC Graphic: Overall study design. C_FIG

A hybrid in silico approach reveals novel inhibitors of multiple SARS-CoV-2 variants

The National Center for Advancing Translational Sciences (NCATS) has been actively generating SARS-CoV-2 high-throughput screening data and disseminates it through the OpenData Portal (https://opendata.ncats.nih.gov/covid19/). Here, we provide a hybrid approach that utilizes NCATS screening data from the SARS-CoV-2 cytophatic effect reduction assay to build predictive models, using both machine learning and pharmacophore-based modeling. Optimized models were used to perform two iterative rounds of virtual screening to predict small molecules active against SARS-CoV-2. Experimental testing with live virus provided 100 (~16% of predicted hits) active compounds (Efficacy > 30%, IC50 [≤] 15 M). Systematic clustering analysis of active compounds revealed three promising chemotypes which have not been previously identified as inhibitors of SARS-CoV-2 infection. Further analysis identified allosteric binders to host receptor angiotensin-converting enzyme 2, which were able to inhibit the entry of pseudoparticles bearing spike protein of wild type SARS-CoV-2 as well as South African B.1.351 and UK B.1.1.7 variants.

Web-based Secure Access from Multiple Patient Reservoirs / 대한의료정보학회지

OBJECTIVE: For the ubiquity of medical service, when user who has proper authority want to access medical data, user accessability should be assured. And the security of the disclosed medical data is important. This paper presents single user access interface on multiple patient reservoirs and elaborate access control using the Role-Based Access Control(RBAC) system. METHODS: Proposed system consists of 4-tier architecture that is client application, Access Control Central(ACC) agent, Local Access Control(LAC) agent and Hospital Information Systems(HIS). User requests medical data with client application. ACC notarizes user identity and controls access of user request and selectively encrypts medical data. LAC charges data conversion for communication between ACC and HIS. HIS has repositories of medical datum. System provides security service with digital certificate, X.509v3, of user. RESULTS: User requests medical data of several HIS approaching single ACC not by each HIS. Through conversion process of LAC, data that is described XML and is used for communication inter system enables information exchange with single common data format that is independent to several HIS. CONCLUSION: In the proposed system, user accesses medical datum of several HIS regardless of location and has consistent access interface. And using independent format against each HIS makes easy information exchange between several HIS. Transferred data maintains security about significant datum by selective encryption and increases encryption efficiency. Unified access control about multiple patient reservoirs that are scattered in other places provides unified and precise diagnosis of patient information. And it functions the portal of collaborate treatment in inter-HIS.

A Randomized, Double-Blind Clinical Trial to Determine the Efficacy of Carvedilol vs. Atenolol in Patients with Stage 1 to 2 Essential Hypertension

BACKGROUND: Carvedilol, an antihypertensive agent with beta-blocking and vasodilating pro-perties, has been demonstrated to be effective in reducing blood pressure. The purpose of this study is to compare the antihypertensive efficacy, safety and tolerability of carvedilol and atenolol in patients with stage 1 to 2 essential hypertension. METHODS: In this double-blind, double-dummy, randomized, parallel study, the efficacy, safety and tolerability of once-daily carvedilol versus once-daily atenolol were evaluated in 58 patients for 8 weeks with stage 1-2 hypertension. If mean peak sitting diastolic blood pressure was equal to or greater than 90mmHg after a 4 week treatment period, the dosage for both study drugs were doubled until the end of study. RESULTS: Data from 58 of 73 patients who completed the study were eligible for per-protocol analysis. At 4 weeks post treatment commencement, mean reductions in peak sitting diastolic blood pressure were 13.9mmHg (95% confidence interval 17.1-11.4) with 25mg carvedilol and 13.6mmHg (95% confidence interval 16.8-10.3) with 50mg atenolol. After the 8 week treatment period with dose titration, mean reductions in peak sitting diastolic blood pressure were 14.7mmHg (95% confidence interval 17.8-11.6) with 50mg carvedilol and 13.6mmHg (95% confidence interval 17.3-9.9) with 100mg atenolol. There were no statistically significant differences between the two treatments in the percentage of patients achieving a normalized blood pressure or in the degree of change in mean peak sitting diastolic blood pressure. Safety profiles were similar between treatments. One patient withdrew due to severe bradycardia development during the second week of treatment with atenolol. CONCLUSION: In patients with mild to moderate hypertension, there were no significant differences between the efficacy of carvedilol or atenolol with regard to antihypertensive effect. Both carvedilol and atenolol were well tolerated with similar safety profiles.

Efficacy of Doppler Contrast Enhancement to Evaluate the Pulmonary Vein Flow

BACKGROUND: Sometimes adequate pulmonary venous flow signal could not be obtained in transthoracic echocardiogram. It has been reported that contrast agent that has transpulmonary passage capability could be used in the enhancement of Doppler signal in the left side of the heart. We evaluated the Levovist(R)-enhanced pulmonary vein flow signals obtained by transthoracic echocardiogram and compared with those obtained by transesophageal echocardiogram. METHOD: Ten patients(male 8, female 10, mean age 46+/-11) with sinus rhythm who underwent transesophageal echocardiogram were enrolled. Spectral Doppler signal intensity(score; 0-5), systolic time velocity integral(Stvi), diastolic time velocity integral(Dtvi) of pulmonary vein flow before and after intravenous injection of the contrast were obtained and compared with those obtained by transesophageal echocardiogram. RESULTS: There was no serious side effect related to Levovist(R). Spectral Doppler signal intensity score of pulmonary vein flow with nonenhanced transthoracic echocardiogram was 2.1 / 5, and adequate Doppler signal could not be obtained in two patients. After contrast enhancement, Doppler signal intensity score rose up to 4.3 / 5 and adequate Doppler signal could be obtained in all patients. Time velocity integrals of systolic and diastolic pulmonary vein flow obtained by transthoracic echocardiogram correlated well with those obtained by transesophageal echocardiogram. CONCLUSION: Contrast enhancement of Doppler signal with the agent that has transpulmonary passage capability(Levovist(R)) is useful in the evaluation of pulmonary vein flow in patient whose transthoracic echocardiographic Doppler signal is inadequate.

Clinical experience on split thickness skin graft from the scalp

No abstract available.

A three year experience with face lift of the Korean(319 procedures)

No abstract available.

Correction of congenital microtia using the tissue expanders

No abstract available.