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2.
Trials ; 24(1): 221, 2023 Mar 23.
Article in English | MEDLINE | ID: covidwho-2268764

ABSTRACT

BACKGROUND: Perirenal fat plays a key role in sustaining pathological high blood pressure. We aim to investigate the efficacy of intervention for perirenal fat mediated by focused power ultrasound (FPU) on primary hypertension. METHODS: A multicenter, randomized, sham-controlled, double-blinded trial will be implemented in 200 participants with mild to moderate hypertension. All enrolled participants will be randomly allocated to perirenal fat modification (PFM) intervention using FPU or sham-procedure at a ratio of 1:1 and will be followed up at 24 h, 14 days, 30 days, and 90 days after the intervention. The primary endpoint is changes in office systolic blood pressure (SBP) at 30 days compared with baseline. The secondary endpoints include the changes in office SBP from baseline to 90 days, changes in 24-h mean SBP from baseline to 30 days and 90 days, and changes in heart rate from baseline to 30 days. Safety endpoint is defined as any severe adverse events related to the intervention. DISCUSSION: The present study is the first to use noninvasive FPU to intervene in perirenal fat to achieve the goal of reducing blood pressure for patients with essential hypertension. Our study is expected to provide a new treatment strategy to control high blood pressure. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05049096. Registered on September 7, 2021. PROTOCOL VERSION: Version 1.3.1, data 23 August 2021. SPONSOR: Prof. Xiangqing Kong is the principal investigator of this trial.


Subject(s)
COVID-19 , Hypertension , Humans , SARS-CoV-2 , Kidney/diagnostic imaging , Hypertension/diagnostic imaging , Hypertension/therapy , Essential Hypertension , Treatment Outcome , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
3.
Crystals ; 13(2):359.0, 2023.
Article in English | MDPI | ID: covidwho-2246817

ABSTRACT

The rapid worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a series of problems. Detection platforms based on graphene field-effect transistors (GFETs) have been proposed to achieve a rapid diagnosis of SARS-CoV-2 antigen or antibody. For GFET-based biosensors, the graphene surface usually needs to be functionalized to immobilize the bioreceptor and the non-covalent approach is preferred for functionalization because it is believed not to significantly alter the electronic properties of graphene. However, in this work, the non-covalent functionalization introduced by 1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE) was determined to lead to different changes in electrical properties in graphene samples with different defect densities. The fabricated graphene biosensor can successfully detect SARS-CoV-2 antigen with a concentration as low as 0.91 pg/mL. Further, by careful comparison, we determined that, for GFET fabricated on graphene with a higher defect density, the current variation caused by PBASE modification is greater and the background current noise in the subsequent antigen detection is also larger. Based on this relationship, we can predict the background current noise of the biosensors by evaluating the current change induced by the modification and screen the devices at an early stage of graphene biosensor fabrication for process optimization.

4.
Front Cell Infect Microbiol ; 12: 1060031, 2022.
Article in English | MEDLINE | ID: covidwho-2198721

ABSTRACT

Introduction: To analyze the current state, hotspots, and cutting-edge trends of genomics research on the outbreak of Corona Virus Disease 2019 (COVID-19) from 2019 to the present (March 2022). Methods: Statistical and visual analysis of COVID-19 genomics results published in the 2019-2022 Web of Science Core Collection Database (WOSCC) was performed using CiteSpace software, including data on countries, institutions, authors, journals, co-citations, keywords, etc. Results: A total of 9133 English literature were included. The number of publications has significantly increased in 2021, and it is expected that this upward trend will last into the future. The research hotspots of COVID-19 revolve around quarantine, biological management, angiotensin-converting enzyme-2, RNA-dependent RNA polymerase, etc. Research frontiers and trends focus on molecular docking, messenger RNA, functional receptor, etc. Conclusion: The last two years have seen a significant increase in research interest in the field of novel coronavirus pneumonia genomics.


Subject(s)
COVID-19 , Humans , Molecular Docking Simulation , Bibliometrics , Genomics , Software
5.
Chinese Journal of Endemiology ; 40(8):616-621, 2021.
Article in Chinese | GIM | ID: covidwho-2055471

ABSTRACT

Objective: To investigate the risk factors of proteinuria in patients with hypertension in Qinghai-Tibet Plateau.

6.
Journal of International Students ; 12:68-87, 2022.
Article in English | ProQuest Central | ID: covidwho-2002868

ABSTRACT

It is well established that international education can profoundly influence a student, including identity and agency formation and the acquisition of knowledge and culture. This study applies the concept of self-formation to reconceptualize the international student experience. It captures the development, changes, and operation of identity and agency during self-formation. Utilizing collective autoethnography, the authentic experiences of three international students studying in Australia during the Covid-19 pandemic were collected. These stories illustrate their transformation from international students to student researchers. Through thematic analysis, three phases have been identified in this study, which are self-exploration, self-positioning, and self-determination and shedding light on the role of agency and hybrid identity. A further scholarly investigation is advocated to enrich the discussion of self-formation and add a nuanced investigation into the variability of individual experiences.

7.
J Perinatol ; 42(10): 1328-1337, 2022 10.
Article in English | MEDLINE | ID: covidwho-1972567

ABSTRACT

OBJECTIVE: We examined the relationship between trimester of SARS-CoV-2 infection, illness severity, and risk for preterm birth. STUDY DESIGN: We analyzed data for 6336 pregnant persons with SARS-CoV-2 infection in 2020 in the United States. Risk ratios for preterm birth were calculated for illness severity, trimester of infection, and illness severity stratified by trimester of infection adjusted for age, selected underlying medical conditions, and pregnancy complications. RESULT: Pregnant persons with critical COVID-19 or asymptomatic infection, compared to mild COVID-19, in the second or third trimester were at increased risk of preterm birth. Pregnant persons with moderate-to-severe COVID-19 did not show increased risk of preterm birth in any trimester. CONCLUSION: Critical COVID-19 in the second or third trimester was associated with increased risk of preterm birth. This finding can be used to guide prevention strategies, including vaccination, and inform clinical practices for pregnant persons.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Premature Birth , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome , Premature Birth/epidemiology , SARS-CoV-2 , United States/epidemiology
8.
Front Microbiol ; 12: 803031, 2021.
Article in English | MEDLINE | ID: covidwho-1753384

ABSTRACT

Background: COVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population. Methods: We collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients' sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays. Results: We found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10-11 months) and one and a half years (17-18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age. Conclusions: We concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.

9.
Front Psychol ; 12: 811078, 2021.
Article in English | MEDLINE | ID: covidwho-1674383

ABSTRACT

PURPOSE: This study aims to examine the mediating role recovery plays in the relationship between resilience and posttraumatic growth (PTG) among breast cancer patients. METHODS: A cross-sectional study design was implemented between January 02, 2021 and April 29, 2021. A total of 789 breast cancer patients from eight hospitals in Liaoning province were selected for participation in this study. These participants completed questionnaires, which included the Post-Traumatic Growth Inventory, EGO Resilience Scale and the Questionnaire about the Process of Recovery. The associated factors of PTG were analyzed using hierarchical multiple regression (HMR). The proposed relationships among resilience, recovery, and PTG were checked by structural equation modeling (SEM) analyses. RESULTS: The average PTG score of breast cancer patients was 53.00 ± 28.30. PTG was positively correlated with both recovery and PTG (a*b = 0.1, BCa95% CI: 0.154 ∼ 0.054). CONCLUSION: Breast cancer patients were found to exhibit a moderate degree of PTG. Resilience was positively associated with PTG and recovery mediated the positive effect of resilience on PTG. Resilience might serve as a crucial protective factor that could explain positive growth in life-threatening illnesses through the mediating path of recovery.

10.
Chinese Journal of School Health ; 42(3):371-374, 2021.
Article in Chinese | CAB Abstracts | ID: covidwho-1498070

ABSTRACT

Objective: To understand the willingness and associated factors with novel coronavirus vaccination ('COVID-19 vaccination') among parents of primary and middle school students in Tongzhou District of Beijing, and to provide reference for studying the feasibility of COVID-19 vaccination among students.

11.
Energies ; 14(9):2352, 2021.
Article in English | ProQuest Central | ID: covidwho-1231447

ABSTRACT

Enhancing forecasting performance in terms of both the expected mean value and variance has been a critical challenging issue for energy industry. In this paper, the novel methodology of finite mixture Generalized AutoRegressive Conditional Heteroskedasticity (GARCH) approach with Expectation–Maximization (EM) algorithm is introduced. The applicability of this methodology is comprehensively evaluated for the forecasting of energy related time series including wind speed, wind power generation, and electricity price. Its forecasting performances are evaluated by various criteria, and also compared with those of the conventional AutoRegressive Moving-Average (ARMA) model and the less conventional ARMA-GARCH model. It is found that the proposed mixture GARCH model outperforms the other two models in terms of volatility modeling for all the energy related time series considered. This is proven to be statistically significant because the p-values of likelihood ratio test are less than 0.0001. On the other hand, in terms of estimations of mean wind speed, mean wind power output, and mean electricity price, no significant improvement from the proposed model is obtained. The results indicate that the proposed finite mixture GARCH model is a viable approach for mitigating the associated risk in energy related predictions thanks to the reduced errors on volatility modeling.

12.
J Med Virol ; 93(1): 472-480, 2021 01.
Article in English | MEDLINE | ID: covidwho-1206789

ABSTRACT

During the early stages of the pandemic, some coronavirus disease (COVID-19) patients were misdiagnosed as having influenza, which aroused the concern that some deaths attributed to influenza were actually COVID-19-related. However, little is known about whether coinfection with influenza contributes to severity of COVID-19 pneumonia, and the optimal therapeutic strategy for these patients. We retrospectively studied 128 hospitalized patients with COVID-19 pneumonia. All patients were positive severe acute respiratory syndrome coronavirus 2 positive by nucleic acid detection. Sixty-four cases were coinfected with influenza A/B and the other 64 were influenza negative, matched by age, sex, and days from onset of symptoms. Among the 64 coinfected patients, 54 (84.4%) were coinfected with influenza A, and 10 (15.6%) with influenza B. The median duration of viral shedding time from admission was longer for patients with influenza coinfection (17.0 days) than for those without influenza coinfection (12.0 days) (P < .001). The multivariable Cox proportional hazards model showed that the hazards ratio of resolution in lung involvement was 1.878 (P = .020) for patients administered lopinavir/ritonavir, compared with those not administered lopinavir/ritonavir (95% confidence interval: 1.103-3.196). Among influenza coinfected patients, those treated with lopinavir/ritonavir exhibited faster pneumonia resolution within 2 weeks after symptom onset (37% vs 1%; P = .001). There was no difference in lung involvement between influenza coinfected and noninfected groups. Lopinavir/ritonavir eliminated the difference of lung involvement between influenza coinfected and noninfected groups, indicating that lopinavir/ritonavir is associated with pneumonia resolution in COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Coinfection/drug therapy , Influenza, Human/drug therapy , Lopinavir/therapeutic use , Pneumonia/drug therapy , Ritonavir/therapeutic use , Aged , COVID-19/virology , Case-Control Studies , Cohort Studies , Drug Therapy, Combination/methods , Female , Hospitalization , Humans , Influenza, Human/virology , Male , Middle Aged , Pandemics/prevention & control , Pneumonia/virology , Retrospective Studies , SARS-CoV-2/drug effects , Virus Shedding/drug effects
13.
J Glob Health ; 11: 05006, 2021 Mar 27.
Article in English | MEDLINE | ID: covidwho-1173056

ABSTRACT

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread throughout China. So far, it has caused ~ 4000 deaths in this country. We aimed to systematically characterize clinical features and determine risk factors of sudden death for COVID-19 patients. METHODS: Deceased patients with COVID-19 in Tongji hospital from January 22 to March 23, 2020 were extracted. Patients who died within 24 hours after admission were identified as sudden deaths, and the others formed non-sudden deaths. The differences in clinical characteristics between the two groups were estimated. Risk factors associated with sudden deaths were explored by logistic regression. RESULTS: 281 deceased patients were enrolled in this study. Sudden death occurred in 28 (10.0%) patients, including 4 (14.3%) admitted to the intensive care unit. Fatigue was more common in sudden deaths (11, 47.8%) than in non-sudden deaths (40, 17.2%). Both the count and percentage of eosinophils were lower in sudden deaths than that in non-sudden deaths (P = 0.006 and P = 0.004). Compared with non-sudden deaths, sudden deaths had higher plasma levels of procalcitonin, C-reactive protein, D-dimer, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase, alkaline phosphatase and N-terminal pro-brain natriuretic peptide. There were not significant differences in gender, age, chest CT image features and comorbidities observed. CONCLUSIONS: The differences between the two groups suggested more severe systemic inflammation, multi-organ dysfunction, especially impaired liver and heart function in COVID-19 patients who died suddenly after admission. More researches are needed to verify these points.


Subject(s)
COVID-19/mortality , Death, Sudden/epidemiology , Patient Admission/statistics & numerical data , SARS-CoV-2 , Aged , Cause of Death , China/epidemiology , Death, Sudden/etiology , Female , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
14.
Pharmaceuticals (Basel) ; 14(3)2021 Mar 09.
Article in English | MEDLINE | ID: covidwho-1143552

ABSTRACT

Although death in malaria is attributed to cerebrovascular blockage and anaemia, overwhelming cytokine production can contribute to the severity of the disease. Therefore, mitigation of dysregulated inflammatory signalling may provide further benefit for malaria treatment. Quercetin (3,3',4',5,7-pentahydroxyflavone) is known to inhibit glycogen synthase kinase-3ß (GSK3ß), a potent regulator of both pro- and anti-inflammatory effects. Quercetin is therefore a potential therapeutic to modulate the imbalanced cytokine production during malarial infection. Anti-malarial effects of quercetin were evaluated in murine models of severe and cerebral malaria using Plasmodium berghei NK65 and ANKA strains, respectively. Western blotting and analysis of cytokines were carried out to determine the GSK3ß-mediated cytokine-modulating effects of quercetin in infected animals. Quercetin (25 mg/kg BW) treatment in P. berghei NK65-infected animals resulted in 60.7 ± 2.4% suppression of parasitaemia and significantly decreased serum levels of TNF-α and IFN-γ, whilst levels of IL-10 and IL-4 were elevated significantly. Western analysis revealed that pGSK3ß (Ser9) increased 2.7-fold in the liver of quercetin-treated NK65-infected animals. Treatment of P. berghei ANKA-infected mice with quercetin (15 mg/kg BW) increased (2.3-fold) pGSK3ß (Ser9) in the brains of infected animals. Quercetin is a potential plant-derived therapeutic for malaria on the basis that it can elicit anti-malarial and GSK3ß-mediated cytokine-modulating effects.

15.
Accounting & Finance ; n/a(n/a), 2021.
Article in English | Wiley | ID: covidwho-1124668

ABSTRACT

Abstract The COVID-19 pandemic is significantly disrupting human capital in labour markets. Workforce reductions cause firm outputs to fall and prices to rise, leading to unprecedented economic costs. To quantify the economic costs, we develop a dynamic general equilibrium macroeconomic model that incorporates susceptible?infectious?recovered epidemiology dynamics, where individuals can be healthy, infected or recovered so that evolution of human capital can be well tracked. We characterise optimal public policy responses to the decline in human capital by either isolating susceptible residents from infected residents to reduce the spread of disease or increases in government spending to improve the recovery and death rates.

16.
Clin Transl Immunology ; 10(2): e1251, 2021.
Article in English | MEDLINE | ID: covidwho-1084626

ABSTRACT

OBJECTIVES: We aimed to gain an understanding of the paradox of the immunity in COVID-19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation. METHODS: A total of 280 hospitalised patients with COVID-19 were evaluated for cytokine profiles and clinical features including viral shedding. A mouse model of acute infection by lymphocytic choriomeningitis virus (LCMV) was applied to dissect the relationship between immunological, virological and pathological features. The results from the mouse model were validated by published data set of single-cell RNA sequencing (scRNA-seq) of immune cells in bronchoalveolar lavage fluid (BALF) of COVID-19 patients. RESULTS: The levels of soluble CD25 (sCD25), IL-6, IL-8, IL-10 and TNF-α were higher in severe COVID-19 patients than non-severe cases, but only sCD25 was identified as an independent risk factor for disease severity by multivariable binary logistic regression analysis and showed a positive association with the duration of viral shedding. In agreement with the clinical observation, LCMV-infected mice with high levels of sCD25 demonstrated insufficient anti-viral response and delayed viral clearance. The elevation of sCD25 in mice was mainly contributed by the expansion of CD25+CD8+ T cells that also expressed the highest level of PD-1 with pro-inflammatory potential. The counterpart human CD25+PD-1+ T cells were expanded in BALF of COVID-19 patients with severe disease compared to those with modest disease. CONCLUSION: These results suggest that high levels of sCD25 in COVID-19 patients probably result from insufficient anti-viral immunity and indicate an expansion of pro-inflammatory T cells that contribute to disease severity.

17.
BMJ Open ; 10(11): e041790, 2020 11 10.
Article in English | MEDLINE | ID: covidwho-919177

ABSTRACT

INTRODUCTION: Scholars believe that COVID-19 can be particularly lethal for patients with cancer. Some studies found that COVID-19 appears to be more lethal in patients with lung cancer than in other cancer patients. In order to take appropriate measures to balance a delay in lung cancer treatment against the risk for a potential COVID-19 exposure, we first need to know whether patients with lung cancer have special risks. We aim to conduct a systematic review and meta-analysis to examine differences in terms of presentation and outcomes between patients with lung cancer as opposed to other solid organ cancer after infection with SARS-CoV-2. METHODS AND ANALYSIS: A comprehensive search of published original research studies will be performed in Embase, MEDLINE, Web of Science, WangFangData, CQVIP, COMPENDEX and CNKI. The medRxiv preprint server will also be searched for applicable studies (grey literature). Original research studies will be included if they include patients with: (A) laboratory-confirmed SARS-CoV-2 infection and (B) confirmed solid cancer, and (C) measurable clinical presentation or outcome, such as mortality rate, intensive care unit admission rate, incidence of pneumonia. One author will conduct the electronic database searches, two authors will independently screen studies, two will extract data and two will assess study quality. If I² exceeds 60% for the pooled analysis, we will explore sources of heterogeneity in subgroups of studies. We will use fixed-effect, random-effects or mixed-effects models to estimate the relative risk or OR. If the data reporting allows, a subgroup analysis between non-small cell lung cancer and small cell lung cancer patients will be performed. ETHICS AND DISSEMINATION: The proposed study will not collect individual-level data and, therefore, does not require ethical approval. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42020190118.


Subject(s)
Coronavirus Infections/physiopathology , Lung Neoplasms/epidemiology , Neoplasms/epidemiology , Pneumonia, Viral/physiopathology , Betacoronavirus , COVID-19 , Case-Control Studies , Comorbidity , Coronavirus Infections/mortality , Humans , Intensive Care Units/statistics & numerical data , Meta-Analysis as Topic , Pandemics , Pneumonia, Viral/mortality , SARS-CoV-2 , Systematic Reviews as Topic
18.
Eur J Clin Invest ; 51(3): e13435, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-868107

ABSTRACT

OBJECTIVE: This study aimed to investigate the value of high-flow nasal cannula (HNFC) oxygen therapy in treating patients with severe novel coronavirus pneumonia (COVID-19). METHODS: The clinical data of 22 patients with severe COVID-19 were collected. The heart rate (HR), respiratory rate (RR) and oxygenation index (PO2 /FiO2 ) at 0, 6, 24 and 72 hours after treatment were compared between the HFNC oxygen therapy group and the conventional oxygen therapy (COT) group. In addition, the white blood cell (WBC) count, lymphocyte (L) count, C-reactive protein (CRP) and procalcitonin (PCT) were compared before and at 72 hours after oxygen therapy treatment. RESULTS: The differences at 0 hours between the two groups were not statistically significant. Compared with COT group,in the HFNC oxygen therapy group, HR, RR and PaO2 /FiO2 were better at 6 hours after treatment, PaO2 /FiO2 was better at 24 and 72 hours. After 72 hours, L and CRP had improved in the HFNC oxygen therapy group compared with the COT group, but the differences in WBC and PCT were not statistically significant. The length of stay in the intensive care unit (ICU) and the total length of hospitalization was shorter in the HFNC oxygen therapy group than in the COT group. CONCLUSION: Compared with COT, early application of HFNC oxygen therapy in patients with severe COVID-19 can improve oxygenation and RR, and HFNC oxygen therapy can improve the infection indexes of patients and reduce the length of stay in the ICU of patients. Therefore, it has high clinical application value.


Subject(s)
COVID-19/therapy , Heart Rate/physiology , Oxygen Inhalation Therapy/methods , Oxygen/blood , Respiratory Rate/physiology , Blood Gas Analysis , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/physiopathology , Cannula , Female , Humans , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Oxygen/administration & dosage , Partial Pressure , Procalcitonin/blood , SARS-CoV-2 , Severity of Illness Index
19.
mBio ; 11(5)2020 09 15.
Article in English | MEDLINE | ID: covidwho-772275

ABSTRACT

Membrane-associated RING-CH-type 8 (MARCH8) strongly blocks human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) incorporation into virions by downregulating its cell surface expression, but the mechanism is still unclear. We now report that MARCH8 also blocks the Ebola virus (EBOV) glycoprotein (GP) incorporation via surface downregulation. To understand how these viral fusion proteins are downregulated, we investigated the effects of MARCH8 on EBOV GP maturation and externalization via the conventional secretion pathway. MARCH8 interacted with EBOV GP and furin when detected by immunoprecipitation and retained the GP/furin complex in the Golgi when their location was tracked by a bimolecular fluorescence complementation (BiFC) assay. MARCH8 did not reduce the GP expression or affect the GP modification by high-mannose N-glycans in the endoplasmic reticulum (ER), but it inhibited the formation of complex N-glycans on the GP in the Golgi. Additionally, the GP O-glycosylation and furin-mediated proteolytic cleavage were also inhibited. Moreover, we identified a novel furin cleavage site on EBOV GP and found that only those fully glycosylated GPs were processed by furin and incorporated into virions. Furthermore, the GP shedding and secretion were all blocked by MARCH8. MARCH8 also blocked the furin-mediated cleavage of HIV-1 Env (gp160) and the highly pathogenic avian influenza virus H5N1 hemagglutinin (HA). We conclude that MARCH8 has a very broad antiviral activity by prohibiting different viral fusion proteins from glycosylation and proteolytic cleavage in the Golgi, which inhibits their transport from the Golgi to the plasma membrane and incorporation into virions.IMPORTANCE Enveloped viruses express three classes of fusion proteins that are required for their entry into host cells via mediating virus and cell membrane fusion. Class I fusion proteins are produced from influenza viruses, retroviruses, Ebola viruses, and coronaviruses. They are first synthesized as a type I transmembrane polypeptide precursor that is subsequently glycosylated and oligomerized. Most of these precursors are cleaved en route to the plasma membrane by a cellular protease furin in the late secretory pathway, generating the trimeric N-terminal receptor-binding and C-terminal fusion subunits. Here, we show that a cellular protein, MARCH8, specifically inhibits the furin-mediated cleavage of EBOV GP, HIV-1 Env, and H5N1 HA. Further analyses uncovered that MARCH8 blocked the EBOV GP glycosylation in the Golgi and inhibited its transport from the Golgi to the plasma membrane. Thus, MARCH8 has a very broad antiviral activity by specifically inactivating different viral fusion proteins.


Subject(s)
Ebolavirus/chemistry , Glycoproteins/antagonists & inhibitors , HIV-1/chemistry , Hemagglutinins, Viral/metabolism , Influenza A Virus, H5N1 Subtype/chemistry , Ubiquitin-Protein Ligases/genetics , Viral Envelope Proteins/antagonists & inhibitors , Viral Envelope Proteins/physiology , Animals , Cell Line , Chlorocebus aethiops , Ebolavirus/physiology , Glycosylation , HEK293 Cells , HIV-1/physiology , HeLa Cells , Hep G2 Cells , Humans , Influenza A Virus, H5N1 Subtype/physiology , Protein Binding , THP-1 Cells , Ubiquitin-Protein Ligases/metabolism , Vero Cells , Viral Fusion Proteins/antagonists & inhibitors , Viral Fusion Proteins/metabolism
20.
Naunyn Schmiedebergs Arch Pharmacol ; 394(4): 775-782, 2021 04.
Article in English | MEDLINE | ID: covidwho-746149

ABSTRACT

Hydroxychloroquine (HCQ) has been implicated in antiviral activity in vitro against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is still controversy about whether HCQ should be used for coronavirus disease 2019 (COVID-19) patients due to the conflicting results in different clinical trials. To systematically assess the benefits and harms of HCQ for the treatment of COVID-19. Data sources were systematically searched from Pubmed, Biorxiv, ChiCTR, Clinicalrials.gov , and the Cochrane library of RCTs for studies published from inception to June 1, 2020, to obtain any possible inclusion. This meta-analysis of inclusion criteria was directed on the basis of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). Pooled studies by the title and abstract were screened and removed in the light of meta-analysis by two reviewers. Seven studies involving 851 participants with COVID-19 were eligible for analysis. There was no significant difference in RT-PCR negative conversion between HCQ group and standard treatment (ST) group (RR = 1.11, 95% CI = 0.77-1.59, P = 0.591). The rate of exacerbated pneumonia on chest CT in HCQ group was lower than that in ST group (RR = 0.44, 95% CI = 0.20-0.94, P = 0.035). There was no statistical difference in progressed illness between the HCQ group and the ST group (RR = 0.66, 95% CI = 0.18-2.43, P = 0.530). Death (RR = 1.92, 95% CI = 1.26-2.93, P = 0.003) was distinctly different in HCQ group compared with ST group in the treatment of COVID-19. Our meta-analysis demonstrated that there was no robust evidence to support prescribing HCQ as a treatment for COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Hydroxychloroquine/therapeutic use , Adult , Antiviral Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Disease Progression , Evidence-Based Medicine , Female , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , Treatment Outcome
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