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1.
Antiviral Res ; 205: 105381, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1982553

ABSTRACT

SARS-CoV-2 has raised the alarm to search for effective therapy for this virus. To date several vaccines have been approved but few available drugs reported recently still need approval from FDA. Remdesivir was approved for emergency use only. In this report, the SARS-CoV-2 3CLpro was expressed and purified. By using a FRET-based enzymatic assay, we have screened a library consisting of more than 300 different niclosamide derivatives and identified three molecules JMX0286, JMX0301, and JMX0941 as potent allosteric inhibitors against SARS-CoV-2 3CLpro, with IC50 values similar to that of known covalent inhibitor boceprevir. In a cell-based antiviral assay, these inhibitors can inhibit the virus growth with EC50 in the range of 2-3 µM. The mechanism of action of JMX0286, JMX0301, and JMX0941 were characterized by enzyme kinetics, affinity binding and protein-based substrate digestion. Molecular docking, molecular dynamics (MD) simulations and hydration studies suggested that JMX0286, JMX0301, JMX0941 bind specifically to an allosteric pocket of the SARS-CoV-2 3CL protease. This study provides three potent compounds for further studies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Coronavirus 3C Proteases , Cysteine Endopeptidases/metabolism , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases/metabolism , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Viral Nonstructural Proteins
2.
Prog Neuropsychopharmacol Biol Psychiatry ; 118: 110578, 2022 08 30.
Article in English | MEDLINE | ID: covidwho-1864636

ABSTRACT

Emerging evidence suggested that people with severe mental disorders were more vulnerable to the negative effects of the COVID-19 pandemic. However, few researches investigated the influence of global pandemics on people at clinical high risk (CHR) for psychosis. This study aimed to investigate the impact of the COVID-19 pandemic on clinical symptoms, psychological distress, and eye-tracking characteristics in CHR individuals and healthy participants. Forty-nine CHR individuals and 50 healthy controls (HC) were assessed by PTSD Checklist for DSM-5 (PCL-5), Perceived Stress Scale, 10-item version (PSS-10), and Coronavirus Impact Scale (CIS). Eye movement performances were measured by the tests of fixation stability, free-viewing, and anti-saccade. According to the mean score of CIS, participants were stratified into high-impact (n = 35) and low-impact (n = 64) subgroups. Compared with the HC group, CHR participants reported significantly higher levels of post-traumatic symptoms caused by the COVID-19 pandemic and showed abnormalities in most of the eye movement indexes. Among the altered indexes, the saccade amplitude of fixation stability test (far distractor), the scan path length of free-viewing test, and the accuracy of anti-saccade test were negatively affected by the severity of impact level in the CHR group. Moreover, the altered eye movement indexes were significantly associated with the total scores of CIS, PCL-5, and subscales of the Scale of Prodromal Syndromes (SOPS) among CHR individuals. Overall, our findings suggested the negative impact of the COVID-19 pandemic on the eye movement characteristics of CHR individuals. The present study provides valuable information on physiological distress related to the COVID-19 pandemic and sensitive neuropsychological biomarkers that interacted with social and environment stress in the CHR population.


Subject(s)
COVID-19 , Psychotic Disorders , COVID-19/epidemiology , Eye-Tracking Technology , Humans , Pandemics , Prodromal Symptoms , Psychotic Disorders/psychology
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322246

ABSTRACT

Background: Currently, coronavirus disease 2019 (COVID-19) has spread worldwide and become a global health concern. Here, we report a familial cluster of COVID-19 infection in a northern Chinese region and share our local experience. Methods A familial cluster of six patients infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) was included for analysis. The demographic data, clinical features, laboratory examinations, and epidemiological characteristics of enrolled cases were collected and analyzed. Results Two family members (Cases 1 and 2) had Hubei exposure history and were admitted to the hospital with a confirmed diagnosis of COVID-19;eight familial members who had contact with them during the incubation period were isolated in a hospital. Finally, the condition of four members (Cases 3, 4, 5, and 6) was as follows. Case 3 had negative SARS-CoV-2 RT-PCR results but was suspected to have COVID-19 because of radiographic abnormalities. Cases 4 and 5 developed COVID-19. Due to positive SARS-CoV-2 RT-PCR results, Case 6 was considered an asymptomatic carrier. In addition, four close contacts did not have evidence of SARS-CoV-2 infection. Conclusions Our findings suggest that COVID-19 has infectivity during the incubation period and preventive quarantine is effective for controlling an outbreak of COVID-19 infection.

4.
Genomics and Applied Biology ; 39(8):3881-3885, 2020.
Article in Chinese | GIM | ID: covidwho-1497992

ABSTRACT

To provide scientific theoretical reference for diagnosis and treatment of patients with SARS-CoV-2 infection, this study collected typical COVID-19 patients' pathological reports and analyzed the pathological characteristics of the important systems and parts of human body, including respiratory system, circulatory system, digestive system, genitourinary system, nervous system and eye. Cytokine release syndrome(CRS), a common cause of death in COVID-19 patients, was discussed in this research.

5.
Am J Trop Med Hyg ; 106(1): 127-131, 2021 10 29.
Article in English | MEDLINE | ID: covidwho-1497592

ABSTRACT

This article aims to understand the changes in the detection rates of H5, H7, and H9 subtypes of avian influenza viruses (AIVs) in the live poultry markets (LPMs) in Nanchang City, Jiangxi Province, before and after the outbreak of the COVID-19. From 2019 to 2020, we monitored the LPM and collected specimens, using real-time reverse transcription polymerase chain reaction technology to detect the nucleic acid of type A AIV in the samples. The H5, H7, and H9 subtypes of influenza viruses were further classified for positive results. We analyzed 1,959 samples before and after the outbreak and found that the positive rates of avian influenza A virus (39.69%) and H9 subtype (30.66%) after the outbreak were significantly higher than before the outbreak (26.84% and 20.90%, respectively; P < 0.001). In various LPMs, the positive rate of H9 subtypes has increased significantly (P ≤ 0.001). Positive rates of the H9 subtype in duck, fecal, daub, and sewage samples, but not chicken samples, have increased to varying degrees. This study shows that additional measures are needed to strengthen the control of AIVs now that LPMs have reopened after the relaxing of COVID-19-related restrictions.


Subject(s)
COVID-19/prevention & control , Disease Outbreaks/prevention & control , Influenza A virus/isolation & purification , Influenza in Birds/epidemiology , Animals , COVID-19/epidemiology , China/epidemiology , Ducks/virology , Environmental Microbiology , Feces/virology , Humans , Influenza A Virus, H9N2 Subtype/isolation & purification , Influenza A virus/classification , Poultry , Sewage/virology
7.
Nurs Open ; 8(6): 3527-3537, 2021 11.
Article in English | MEDLINE | ID: covidwho-1220262

ABSTRACT

AIM: To investigate the influencing factors in professional identity of undergraduate nursing students after the outbreak of COVID-19. DESIGN: Cross-sectional study. METHODS: The study covered 2,999 nursing students in six undergraduate nursing schools. Several self-report questionnaires were used to collect the general information, psychological stress, coping styles and professional identity of the undergraduate nursing students. RESULTS: The overall average score of the professional identity of nursing students (3.67 ± 0.51) has increased significantly after the outbreak of COVID-19. The professional identity of the undergraduate nursing students was negatively correlated with psychological stress (r = -0.23, p < .001), expectation (r = -0.12, p < .001) and avoidance (r = -0.16, p < .001), but was positively correlated with solving problems (r = 0.18, p < .001) and seeking support (r = 0.12, p < .001). Academic performance, positions, grades, reasons for choosing a nursing profession, parents or relatives engaged in nursing work and the risk degree of residence were the factors influencing the professional identity score of undergraduate nursing students' (p < .001).


Subject(s)
COVID-19 , Education, Nursing, Baccalaureate , Students, Nursing , Adaptation, Psychological , Cross-Sectional Studies , Disease Outbreaks , Humans , SARS-CoV-2 , Stress, Psychological/epidemiology
9.
Int J Infect Dis ; 110: 247-257, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1188633

ABSTRACT

OBJECTIVES: The novel coronavirus (COVID-19) epidemic is reaching its final phase in China. The epidemic data are available for a complete assessment of epidemiological parameters in all regions and time periods. METHODS: This study aims to present a spatiotemporal epidemic model based on spatially stratified heterogeneity (SSH) to simulate the epidemic spread. A susceptible-exposed/latent-infected-removed (SEIR) model was constructed for each SSH-identified stratum (each administrative city) to estimate the spatiotemporal epidemiological parameters of the outbreak. RESULTS: We estimated that the mean latent and removed periods were 5.40 and 2.13 days, respectively. There was an average of 1.72 latent or infected persons per 10,000 Wuhan travelers to other locations until January 20th, 2020. The space-time basic reproduction number (R0) estimates indicate an initial value between 2 and 3.5 in most cities on this date. The mean period for R0 estimates to decrease to 80%, and 50% of initial values in cities were an average of 14.73 and 19.62 days, respectively. CONCLUSIONS: Our model estimates the complete spatiotemporal epidemiological characteristics of the outbreak in a space-time domain. These findings will help enhance a comprehensive understanding of the outbreak and inform the strategies of prevention and control in other countries worldwide.


Subject(s)
COVID-19 , Epidemics , Basic Reproduction Number , China/epidemiology , Humans , SARS-CoV-2
10.
Virulence ; 11(1): 482-485, 2020 12.
Article in English | MEDLINE | ID: covidwho-343283

ABSTRACT

Since its outbreak in Wuhan, Hubei Province China, 2019-coronavirus infected disease (COVID-19) had been widely spread all over the world, the control of which calls for a better understanding of its epidemiology and clinical characteristics. We included 12 confirmed cases of COVID-19 in First Affiliated Hospital of Jilin University from 23 January 2020 to 11 February 2020, which were retrospectively analyzed for epidemiological, demographic, clinical, laboratory, and radiological features. All the patients were confirmed by nucleic acid detection, the average age of whom was 45.25 years (range, 23-79 years). Most patients had a history of Wuhan traveling or had contact with Wuhan travelers or infected cases. Obvious family cluster was observed. Clinical manifestations included fever (12/12), fatigue (10/12), cough (6/12), sore throat (4/12), headache (3/12), and diarrhea (2/12). Only three out of eight patients had pneumonia manifestation on radiography. Most patients had a normal white blood cell (WBC) count and normal or reduced lymphocyte (LY) count. Pneumonia changes were observed in all the four patients who underwent a chest CT scan. Only one elderly patient developed severe pneumonia, while all the rest were mild disease and had a self-limiting course.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Adult , Aged , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/virology , Cough/etiology , Diarrhea/etiology , Fatigue/etiology , Female , Fever/etiology , Headache/etiology , Humans , Leukocyte Count , Male , Middle Aged , Pandemics , Pharyngitis/etiology , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
11.
Int J Infect Dis ; 96: 489-495, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-276634

ABSTRACT

OBJECTIVES: The outbreak of atypical pneumonia caused by the novel coronavirus (COVID-19) has currently become a global concern. The generations of the epidemic spread are not well known, yet these are critical parameters to facilitate an understanding of the epidemic. A seafood wholesale market and Wuhan city, China, were recognized as the primary and secondary epidemic sources. Human movements nationwide from the two epidemic sources revealed the characteristics of the first-generation and second-generation spreads of the COVID-19 epidemic, as well as the potential third-generation spread. METHODS: We used spatiotemporal data of COVID-19 cases in mainland China and two categories of location-based service (LBS) data of mobile devices from the primary and secondary epidemic sources to calculate Pearson correlation coefficient,r, and spatial stratified heterogeneity, q, statistics. RESULTS: Two categories of device trajectories had generally significant correlations and determinant powers of the epidemic spread. Bothr and q statistics decreased with distance from the epidemic sources and their associations changed with time. At the beginning of the epidemic, the mixed first-generation and second-generation spreads appeared in most cities with confirmed cases. They strongly interacted to enhance the epidemic in Hubei province and the trend was also significant in the provinces adjacent to Hubei. The third-generation spread started in Wuhan from January 17-20, 2020, and in Hubei from January 23-24. No obvious third-generation spread was detected outside Hubei. CONCLUSIONS: The findings provide important foundations to quantify the effect of human movement on epidemic spread and inform ongoing control strategies. The spatiotemporal association between the epidemic spread and human movements from the primary and secondary epidemic sources indicates a transfer from second to third generations of the infection. Urgent control measures include preventing the potential third-generation spread in mainland China, eliminating it in Hubei, and reducing the interaction influence of first-generation and second-generation spreads.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , COVID-19 , China/epidemiology , Disease Outbreaks , Epidemics , Humans , Pandemics , SARS-CoV-2 , Wireless Technology
12.
Brain Behav Immun ; 88: 17-27, 2020 08.
Article in English | MEDLINE | ID: covidwho-270288

ABSTRACT

Since the end of 2019, Corona Virus Disease 2019 (COVID-19) has been the cause of a worldwide pandemic. The mental status of patients with COVID-19 who have been quarantined and the interactions between their psychological distress and physiological levels of inflammation have yet to be analyzed. Using a mixed-method triangulation design (QUAN + QUAL), this study investigated and compared the mental status and inflammatory markers of 103 patients who, while hospitalized with mild symptoms, tested positive with COVID-19 and 103 matched controls that were COVID-19 negative. The severity of depression, anxiety, and post-traumatic stress symptoms (PTSS) was measured via an on-line survey. Using a convenience sampling technique, qualitative data were collected until the point of data saturation. In addition, a semi-structured interview was conducted among five patients with COVID-19. Peripheral inflammatory markers were also collected in patients, both at baseline and within ± three days of completing the on-line survey. Results revealed that COVID-19 patients, when compared to non-COVID controls, manifested higher levels of depression (P < 0.001), anxiety (P < 0.001), and post-traumatic stress symptoms (P < 0.001). A gender effect was observed in the score of "Perceived Helplessness", the subscale of PSS-10, with female patients showing higher scores compared to male patients (Z = 2.56, P = 0.010), female (Z = 2.37, P = 0.018) and male controls (Z = 2.87, P = 0.004). Levels of CRP, a peripheral inflammatory indicator, correlated positively with the PHQ-9 total score (R = 0.37, P = 0.003, Spearman's correlation) of patients who presented symptoms of depression. Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (R = -0.31, P = 0.002), indicative of improvement of depression symptoms. Qualitative analysis revealed similar results with respect to patient reports of negative feelings, including fear, guilt, and helplessness. Stigma and uncertainty of viral disease progression were two main concerns expressed by COVID-19 patients. Our results indicate that significant psychological distress was experienced by hospitalized COVID-19 patients and that levels of depressive features may be related to the inflammation markers in these patients. Thus, we recommend that necessary measures should be provided to address depression and other psychiatric symptoms for COVID-19 patients and attention should be paid to patient perceived stigma and coping strategies when delivering psychological interventions.


Subject(s)
Anxiety/psychology , C-Reactive Protein/immunology , Coronavirus Infections/psychology , Depression/psychology , Inflammation/immunology , Pneumonia, Viral/psychology , Psychological Distress , Quarantine/psychology , Stress, Psychological/psychology , Adult , Aged , Anxiety/immunology , Betacoronavirus , Blood Sedimentation , COVID-19 , Case-Control Studies , Coronavirus Infections/immunology , Cross-Sectional Studies , Depression/immunology , Female , Hospitalization , Humans , Leukocyte Count , Male , Middle Aged , Pandemics , Patient Health Questionnaire , Pneumonia, Viral/immunology , Procalcitonin/immunology , SARS-CoV-2 , Sex Factors , Stress Disorders, Post-Traumatic/immunology , Stress Disorders, Post-Traumatic/psychology , Stress, Psychological/immunology
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