Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
1.
RSC Adv ; 12(48): 31441, 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2106535

ABSTRACT

[This corrects the article DOI: 10.1039/D2RA04162F.].

2.
Journal of Pharmaceutical and Biomedical Analysis ; : 115118, 2022.
Article in English | ScienceDirect | ID: covidwho-2083231

ABSTRACT

Coronavirus disease (COVID-19) caused by SARS-COV-2 infection has been widely prevalent in many countries and has become a common challenge facing mankind. Traditional Chinese medicine (TCM) has played a prominent role in this pandemic, and especially TCM with the function of “heat-clearing and detoxifying” has shown an excellent role in anti-virus. Fufang Shuanghua oral liquid (FFSH) has been used to treat the corresponding symptoms of influenza such as fever, nasal congestion, runny nose, sore throat, and upper respiratory tract infections in clinic, which are typical symptoms of COVID-19. The content of chlorogenic acid, andrographolide and dehydrated andrographolide as the quality control components of FFSH is not less than 1.0mg/mL, 60μg/mL and 60μg/mL respectively. In this study, UPLC-Q-TOF-MS/MS was employed to describe the chemical profile of FFSH. Virtual screening and fluorescence resonance energy transfer (FRET) were used to screen the effective components of FFSH acting on SARS-CoV-2 main protease (Mpro). As a result, 214 compounds in FFSH were identified or preliminarily characterized by UPLC-Q-TOF-MS/MS, and 61 active ingredients with potential inhibitory effects on Mpro were selected through receptor-based and ligand-based virtual screening. In particular, quercetin, forsythoside A, and linoleic acid showed a good inhibitory effect on Mpro in FRET evaluation with IC50 values of 26.15μM, 22.26μM and 47.09μM respectively, and had a strong binding affinity with the receptor Mpro (6LU7) in molecular docking. CYS145 and HIS41 were the main amino acid residues affected by small molecules in the protein binding domain. In brief, we characterized, for the first time, 214 chemical components in FFSH, and three of them, including quercetin, forsythoside A and linoleic acid, were screened out to exert beneficial anti-COVID-19 effects through CYS145 and HIS41 sites, which may provide a new research strategy for TCM to develop new therapeutic drugs against COVID-19.

3.
Anal Chem ; 94(42): 14761-14768, 2022 10 25.
Article in English | MEDLINE | ID: covidwho-2062140

ABSTRACT

Antibody drugs have been rapidly developed to cure many diseases including COVID-19 infection. Silicone oil is commonly used as a lubricant coating material for devices used in the pharmaceutical industry to store and administer antibody drug formulations. However, the interaction between silicone oil and antibody molecules could lead to the adsorption, denaturation, and aggregation of antibody molecules, impacting the efficacy of antibody drugs. Here, we studied the molecular interactions between antibodies and silicone oil in situ in real time. The effect of the surfactant on such interactions was also investigated. Specifically, the adsorption dynamics of a bispecific antibody (BsAb) onto a silicone oil surface without and with different concentrations of the surfactant PS80 in antibody solutions were monitored. Also the possible lowest effective PS80 concentrations that can prevent the adsorption of BsAb as well as a monoclonal antibody (mAb) onto silicone oil were measured. It was found that different concentrations of PS80 are required for preventing the adsorption of different antibodies. Both BsAB and mAB denature on silicone oil without a surfactant. However, for a low surfactant concentration in the solution, although the surfactant could not completely prevent the antibody from adsorption, it could maintain the native structures of adsorbed BsAb and mAb antibodies on silicone oil. This is important knowledge, showing that to prevent antibody aggregation on silicone oil it is not necessary to add surfactant to a concentration high enough to completely minimize protein adsorption.


Subject(s)
Antibodies, Bispecific , COVID-19 , Humans , Silicone Oils/chemistry , Surface-Active Agents/chemistry , Excipients/chemistry , Adsorption , Antibodies, Monoclonal/chemistry , Lubricants
5.
RSC Adv ; 12(35): 22592-22607, 2022 Aug 10.
Article in English | MEDLINE | ID: covidwho-1996875

ABSTRACT

The global pandemic of COVID-19, which began in late 2019, has resulted in extremely high morbidity and severe mortality worldwide, with important implications for human health, international trade, and national politics. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is the primary pathogen causing COVID-19. Analytical chemistry played an important role in this global epidemic event, and detection of SARS-CoV-2 even became a part of daily life. Analytical chemists have devoted much effort and enthusiasm to this event, and different analytical techniques have shown very rapid development. Electrochemical biosensors are highly efficient, sensitive, and cost-effective and have been used to detect many highly pathogenic viruses long before this event. However, another fact is that electrochemical biosensors are not the technology of choice for most detection applications. This review describes for the first time the role played by electrochemical biosensors in SARS-CoV-2 detection from a bibliometric perspective. This paper analyzed 254 relevant research papers up to June 2022. The contributions of different countries and institutions to this topic were analyzed. Keyword analysis was used to explore different methodological attempts of electrochemical detection techniques. More importantly, we are trying to find an answer to the question: do electrochemical biosensors have the potential to become a genuinely employable detection technology in an outbreak of infectious disease?

6.
Biomed Pharmacother ; 152: 113230, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1881709

ABSTRACT

BACKGROUND: Bromodomain and extraterminal proteins (BETs) are more than just epigenetic regulators of transcription. Here we highlight a new role for the BET protein BRD4 in the maintenance of higher order chromatin structure at Topologically Associating Domain Boundaries (TADBs). BD2-selective and pan (non-selective) BET inhibitors (BETi) differentially support chromatin structure, selectively affecting transcription and cell viability. METHODS: Using RNA-seq and BRD4 ChIP-seq, the differential effect of BETi treatment on the transcriptome and BRD4 chromatin occupancy of human aortic endothelial cells from diabetic patients (dHAECs) stimulated with TNFα was evaluated. Chromatin decondensation and DNA fragmentation was assessed by immunofluorescence imaging and quantification. Key dHAEC findings were verified in proliferating monocyte-like THP-1 cells using real time-PCR, BRD4 co-immunoprecipitation studies, western blots, proliferation and apoptosis assays. FINDINGS: We discovered that 1) BRD4 co-localizes with Ying-Yang 1 (YY1) at TADBs, critical chromatin structure complexes proximal to many DNA repair genes. 2) BD2-selective BETi enrich BRD4/YY1 associations, while pan-BETi do not. 3) Failure to support chromatin structures through BRD4/YY1 enrichment inhibits DNA repair gene transcription, which induces DNA damage responses, and causes widespread chromatin decondensation, DNA fragmentation, and apoptosis. 4) BD2-selective BETi maintain high order chromatin structure and cell viability, while reducing deleterious pro-inflammatory transcription. INTERPRETATION: BRD4 plays a previously unrecognized role at TADBs. BETi differentially impact TADB stability. Our results provide translational insight for the development of BETi as therapeutics for a range of diseases including CVD, chronic kidney disease, cancer, and COVID-19.


Subject(s)
COVID-19 , Transcription Factors , Cell Cycle Proteins/metabolism , Chromatin , Endothelial Cells/metabolism , Epigenesis, Genetic , Humans , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Transcription Factors/metabolism
8.
J Nat Prod ; 85(2): 327-336, 2022 02 25.
Article in English | MEDLINE | ID: covidwho-1655431

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 5 million deaths worldwide to date. Due to the limited therapeutic options so far available, target-based virtual screening with LC/MS support was applied to identify the novel and high-content compounds 1-4 with inhibitory effects on SARS-CoV-2 in Vero E6 cells from the plant Dryopteris wallichiana. These compounds were also evaluated against SARS-CoV-2 in Calu-3 cells and showed unambiguous inhibitory activity. The inhibition assay of targets showed that compounds 3 and 4 mainly inhibited SARS-CoV-2 3CLpro, with effective Kd values. Through docking and molecular dynamics modeling, the binding site is described, providing a comprehensive understanding of 3CLpro and interactions for 3, including hydrogen bonds, hydrophobic bonds, and the spatial occupation of the B ring. Compounds 3 and 4 represent new, potential lead compounds for the development of anti-SARS-CoV-2 drugs. This study has led to the development of a target-based virtual screening method for exploring the potency of natural products and for identifying natural bioactive compounds for possible COVID-19 treatment.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , Microbial Sensitivity Tests/methods , Phloroglucinol/pharmacology , SARS-CoV-2/drug effects , Terpenes/pharmacology , Chromatography, High Pressure Liquid , Chromatography, Liquid , Crystallography, X-Ray , Drug Delivery Systems , Dryopteris/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Docking Simulation , Molecular Structure , Virtual Reality
9.
Chinese Journal of Nosocomiology ; 31(21):3691-3694, 2021.
Article in Chinese | CAB Abstracts | ID: covidwho-1628307

ABSTRACT

OBJECTIVE: To investigate the mode of prevention and control during local outbreaks of Corona virus disease 2019 (COVID-19), and to provide a basis for effective prevention of nosocomial infection. METHODS: Based on the working mode of the state council to prevent and control local outbreaks of COVID-19, the national technical guidelines on COVID-19 prevention and control, and the experience of fighting against COVID-19, working mode of nosocomial infection prevention and control team under the new mode were explored and analyzed. RESULTS: COVID-19 nosocomial infection prevention and control required scientific standards, multiple measures and precise control. Infection prevention and control teams should focus on environmental safety and personnel safety. Therefore, the effectiveness of the work should focus on improving the organizational structure, infection risk assessment in designated hospitals, establishing rules and regulations and working processes, establishing working mechanisms, standardizing information reporting and other aspects, and ensuring the implementation of prevention and control measures through supervision, monitoring, training and guidance. CONCLUSION: Nosocomial infection has a serious impact on COVID-19 response. Infection prevention and control teams need to establish a scientific and effective working mode to implement precise policies and scientific prevention and control, which can effectively prevent and control nosocomial infection incidents in COVID-19 response.

10.
Aging (Albany NY) ; 14(2): 544-556, 2022 01 17.
Article in English | MEDLINE | ID: covidwho-1626781

ABSTRACT

The wide spread of coronavirus disease 2019 is currently the most rigorous health threat, and the clinical outcomes of severe patients are extremely poor. In this study, we establish an early warning nomogram model related to severe versus common COVID-19. A total of 1059 COVID-19 patients were analyzed in the primary cohort and divided into common and severe according to the guidelines on the Diagnosis and Treatment of COVID-19 by the National Health Commission of China (7th version). The clinical data were collected for logistic regression analysis to assess the risk factors for severe versus common type. Furthermore, 123 COVID-19 patients were reviewed as the validation cohort to assess the performance of this model. Multivariate logistic analysis revealed that age, dyspnea, lymphocyte count, C-reactive protein and interleukin-6 were independent factors for prewarning the severe type occurrence. Then, the early warning nomogram model including these risk factors for inferring the severe disease occurrence out of common type of COVID-19 was constructed. The C-index of this nomogram in the primary cohort was 0.863, 95% confidence interval (CI) (0.836-0.889). Meanwhile, in the validation cohort, the C-index of this nomogram was 0.889, 95% CI (0.828-0.950). In both the primary cohort and validation cohorts, the calibration curve showed good agreement between prediction and actual probability. The early warning model shows that data at the very beginning including age, dyspnea, lymphocyte count, CRP, and IL-6 may prewarn the severe disease occurrence to some extent, which could help clinicians early and timely treatment.


Subject(s)
COVID-19/mortality , Clinical Decision Rules , Nomograms , Age Factors , COVID-19/pathology , China/epidemiology , Female , Humans , Logistic Models , Male , Multivariate Analysis , ROC Curve , Retrospective Studies , Risk Factors , Sex Factors
11.
Sensors (Basel) ; 21(21)2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1512561

ABSTRACT

Sustained attention is essential for older adults to maintain an active lifestyle, and the deficiency of this function is often associated with health-related risks such as falling and frailty. The present study examined whether the well-established age-effect on reducing mind-wandering, the drift to internal thoughts that are seen to be detrimental to attentional control, could be replicated by using a robotic experimenter for older adults who are not as familiar with online technologies. A total of 28 younger and 22 older adults performed a Sustained Attention to Response Task (SART) by answering thought probes regarding their attention states and providing confidence ratings for their own task performances. The indices from the modified SART suggested a well-documented conservative response strategy endorsed by older adults, which were represented by slower responses and increased omission errors. Moreover, the slower responses and increased omissions were found to be associated with less self-reported mind-wandering, thus showing consistency with their higher subjective ratings of attentional control. Overall, this study demonstrates the potential of constructing age-related cognitive profiles with attention evaluation instruction based on a social companion robot for older adults at home.


Subject(s)
Robotics , Aged , Humans , Memory, Short-Term , Self Report , Social Interaction , Task Performance and Analysis
13.
Circ Cardiovasc Qual Outcomes ; 14(5): e007098, 2021 05.
Article in English | MEDLINE | ID: covidwho-1232381

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted clinical care worldwide. Evidence of how this health crisis affected common conditions like blood pressure (BP) control is uncertain. METHODS: We used longitudinal BP data from an ongoing randomized clinical trial to examine variations in home BP monitored via a smartphone-based application (app) in a total of 7394 elderly patients with hypertension aged 60 to 80 years stratified by their location in Wuhan (n=283) compared with other provinces of China (n=7111). Change in morning systolic BP (SBP) was analyzed for 5 30-day phases during the pandemic, including preepidemic (October 21 to November 20, 2019), incubation (November 21 to December 20, 2019), developing (December 21, 2019 to January 20, 2020), outbreak (January 21 to February 20, 2020), and plateau (February 21 to March 21, 2020). RESULTS: Compared with non-Wuhan areas of China, average morning SBP (adjusted for age, sex, body mass index) in Wuhan patients was significantly higher during the epidemic growth phases, which returned to normal at the plateau. Between-group differences in ΔSBP were +2.5, +3.0, and +2.1 mm Hg at the incubation, developing, and outbreak phases of COVID-19 (P<0.001), respectively. Sensitivity analysis showed a similar trend in trajectory pattern of SBP in both the intensive and standard BP control groups of the trial. Patients in Wuhan also had an increased regimen change in antihypertensive drugs during the outbreak compared with non-Wuhan patients. Expectedly, Wuhan patients were more likely to check their BP via the app, while doctors were less likely to monitor the app for BP control during the pandemic. CONCLUSIONS: Our data demonstrate that the COVID-19 pandemic was associated with a short-term increase in morning SBP among elderly patients with hypertension in Wuhan but not other parts of China. Further study will be needed to understand if these findings extended to other parts of the world substantially affected by the virus. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03015311.


Subject(s)
Blood Pressure Determination , COVID-19/epidemiology , Hypertension/diagnosis , Hypertension/physiopathology , Smartphone , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , China , Female , Humans , Hypertension/therapy , Longitudinal Studies , Male , Middle Aged , Self Care
15.
Biomedicines ; 9(4)2021 Apr 18.
Article in English | MEDLINE | ID: covidwho-1194606

ABSTRACT

Effective therapeutics are urgently needed to counter infection and improve outcomes for patients suffering from COVID-19 and to combat this pandemic. Manipulation of epigenetic machinery to influence viral infectivity of host cells is a relatively unexplored area. The bromodomain and extraterminal (BET) family of epigenetic readers have been reported to modulate SARS-CoV-2 infection. Herein, we demonstrate apabetalone, the most clinical advanced BET inhibitor, downregulates expression of cell surface receptors involved in SARS-CoV-2 entry, including angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase 4 (DPP4 or CD26) in SARS-CoV-2 permissive cells. Moreover, we show that apabetalone inhibits SARS-CoV-2 infection in vitro to levels comparable to those of antiviral agents. Taken together, our study supports further evaluation of apabetalone to treat COVID-19, either alone or in combination with emerging therapeutics.

16.
Mil Med Res ; 8(1): 21, 2021 03 17.
Article in English | MEDLINE | ID: covidwho-1140518

ABSTRACT

BACKGROUND: To develop an effective model of predicting fatal outcomes in the severe coronavirus disease 2019 (COVID-19) patients. METHODS: Between February 20, 2020 and April 4, 2020, consecutive confirmed 2541 COVID-19 patients from three designated hospitals were enrolled in this study. All patients received chest computed tomography (CT) and serological examinations at admission. Laboratory tests included routine blood tests, liver function, renal function, coagulation profile, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and arterial blood gas. The SaO2 was measured using pulse oxygen saturation in room air at resting status. Independent high-risk factors associated with death were analyzed using Cox proportional hazard model. A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients. RESULTS: There were 124 severe patients in the training cohort, and there were 71 and 76 severe patients in the two independent validation cohorts, respectively. Multivariate Cox analysis indicated that age ≥ 70 years (HR = 1.184, 95% CI 1.061-1.321), panting (breathing rate ≥ 30/min) (HR = 3.300, 95% CI 2.509-6.286), lymphocyte count < 1.0 × 109/L (HR = 2.283, 95% CI 1.779-3.267), and interleukin-6 (IL-6) >  10 pg/ml (HR = 3.029, 95% CI 1.567-7.116) were independent high-risk factors associated with fatal outcome. We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort (AUC = 0.900, 95% CI 0.841-0.960, sensitivity 95.5%, specificity 77.5%); in validation cohort 1 (AUC = 0.811, 95% CI 0.763-0.961, sensitivity 77.3%, specificity 73.5%); in validation cohort 2 (AUC = 0.862, 95% CI 0.698-0.924, sensitivity 92.9%, specificity 64.5%). The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation. The prognosis of severe COVID-19 patients with high levels of IL-6 receiving tocilizumab were better than that of those patients without tocilizumab both in the training and validation cohorts, but without difference (P = 0.105 for training cohort, P = 0.133 for validation cohort 1, and P = 0.210 for validation cohort 2). CONCLUSIONS: This nomogram could help clinicians to identify severe patients who have high risk of death, and to develop more appropriate treatment strategies to reduce the mortality of severe patients. Tocilizumab may improve the prognosis of severe COVID-19 patients with high levels of IL-6.


Subject(s)
COVID-19/mortality , Clinical Decision Rules , Nomograms , Acute Disease , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/pathology , China/epidemiology , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sex Factors , Survival Analysis , Young Adult
17.
Cell ; 184(8): 2167-2182.e22, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1135274

ABSTRACT

Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined but could be through direct cardiac infection and/or inflammation-induced dysfunction. To identify mechanisms and cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with phosphoproteomics and single nuclei RNA sequencing. We identify an inflammatory "cytokine-storm", a cocktail of interferon gamma, interleukin 1ß, and poly(I:C), induced diastolic dysfunction. Bromodomain-containing protein 4 is activated along with a viral response that is consistent in both human cardiac organoids (hCOs) and hearts of SARS-CoV-2-infected K18-hACE2 mice. Bromodomain and extraterminal family inhibitors (BETi) recover dysfunction in hCOs and completely prevent cardiac dysfunction and death in a mouse cytokine-storm model. Additionally, BETi decreases transcription of genes in the viral response, decreases ACE2 expression, and reduces SARS-CoV-2 infection of cardiomyocytes. Together, BETi, including the Food and Drug Administration (FDA) breakthrough designated drug, apabetalone, are promising candidates to prevent COVID-19 mediated cardiac damage.


Subject(s)
COVID-19/complications , Cardiotonic Agents/therapeutic use , Cell Cycle Proteins/antagonists & inhibitors , Heart Diseases/drug therapy , Quinazolinones/therapeutic use , Transcription Factors/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/drug therapy , Cell Cycle Proteins/metabolism , Cell Line , Cytokines/metabolism , Female , Heart Diseases/etiology , Human Embryonic Stem Cells , Humans , Inflammation/complications , Inflammation/drug therapy , Mice , Mice, Inbred C57BL , Transcription Factors/metabolism
18.
World Scientific Research Journal ; 6(12):207-221, 2020.
Article in English | Airiti Library | ID: covidwho-994117

ABSTRACT

In the past few months, Coronavirus Disease 2019 (COVID‐19) has spread around the world. Among all the countries, the United States seems to be the one facing severe problems. This project begins with some graphical displays of basic explorations on confirmed and death cases in each state, followed by the application of the "lowess" smoother model on the recent trends of the daily new confirmed cases. Additionally, this project utilizes mathematical models and further graphical tools to investigate the impacts of the "Stay at Home" policy on the daily increment of confirmed cases. "Stay at Home" policy is practical to some extent since most state‐level administrative divisions are seeing a decline in the number of new daily diagnoses. However, the condition for several states is still so severe that they need to reconsider the work resumption or adopt other useful approaches.

19.
Science & Technology Review ; 38(4):15-20, 2020.
Article in Chinese | GIM | ID: covidwho-825186

ABSTRACT

At present, under the firm leadership of the Party Central Committee, the whole nation is fighting against the outbreak of the new coronavirus pneumonia (NCP). This is an serious infectious disease with many new clinical and epidemiological characteristics caused by a coronavirus that has never been found in humans before. For the sake of fighting the epidemic, urgent need for emergency research exists for virus characteristics, pathogenesis, transmission, clinical diagnosis and treatment, scientific prevention and control of NCP. This paper makes a summary of the current domestic and foreign literature on novel coronavirus pneumonia for you to quickly understand this new disease, In order to provide reference for further study of the disease.

20.
Sci Adv ; 6(32): eabb0372, 2020 08.
Article in English | MEDLINE | ID: covidwho-827120

ABSTRACT

Despite the therapeutic success of monoclonal antibodies (mAbs), early identification of developable mAb drug candidates with optimal manufacturability, stability, and delivery attributes remains elusive. Poor solution behavior, which manifests as high solution viscosity or opalescence, profoundly affects the developability of mAb drugs. Using a diverse dataset of 59 mAbs, including 43 approved products, and an array of molecular descriptors spanning colloidal, conformational, charge-based, hydrodynamic, and hydrophobic properties, we show that poor solution behavior is prevalent (>30%) in mAbs and is singularly predicted (>90%) by the diffusion interaction parameter (k D), a dilute-solution measure of colloidal self-interaction. No other descriptor, individually or in combination, was found to be as effective as k D. We also show that well-behaved mAbs, a substantial subset of which bear high positive charge and pI, present no disadvantages with respect to pharmacokinetics in humans. Here, we provide a systematic framework with quantitative thresholds for selecting well-behaved therapeutic mAbs during drug discovery.


Subject(s)
Antibodies, Monoclonal , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/therapeutic use , Diffusion , Humans , Hydrophobic and Hydrophilic Interactions , Viscosity
SELECTION OF CITATIONS
SEARCH DETAIL