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1.
BMJ : British Medical Journal (Online) ; 377, 2022.
Article in English | ProQuest Central | ID: covidwho-1807349

ABSTRACT

ObjectiveTo evaluate sintilimab versus placebo in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) as first line treatment of unresectable locally advanced, recurrent, or metastatic oesophageal squamous cell carcinoma.DesignMulticentre, randomised, double blind, phase 3 trial.Setting66 sites in China and 13 sites outside of China between 14 December 2018 and 9 April 2021.Participants659 adults (aged ≥18 years) with advanced or metastatic oesophageal squamous cell carcinoma who had not received systemic treatment.InterventionParticipants were randomised 1:1 to receive sintilimab or placebo (3 mg/kg in patients weighing <60 kg or 200 mg in patients weighing ≥60 kg) in combination with cisplatin 75 mg/m2 plus paclitaxel 175 mg/m2 every three weeks. The trial was amended to allow investigators to choose the chemotherapy regimen: cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil (800 mg/m2 continuous infusion on days 1-5).Main outcome measuresOverall survival in all patients and in patients with combined positive scores of ≥10 for expression of programmed cell death ligand 1.Results659 patients were randomly assigned to sintilimab (n=327) or placebo (n=332) with chemotherapy. 616 of 659 patients (93%) received sintilimab or placebo in combination with cisplatin plus paclitaxel and 43 of 659 patients (7%) received sintilimab or placebo in combination with cisplatin plus 5-fluorouracil. At the interim analysis, sintilimab with chemotherapy showed better overall survival compared with placebo and chemotherapy in all patients (median 16.7 v 12.5 months, hazard ratio 0.63, 95% confidence interval 0.51 to 0.78, P<0.001) and in patients with combined positive scores of ≥10 (17.2 v 13.6 months, 0.64, 0.48 to 0.85, P=0.002). Sintilimab and chemotherapy significantly improved progression free survival compared with placebo and chemotherapy in all patients (7.2 v 5.7 months, 0.56, 0.46 to 0.68, P<0.001) and in patients with combined positive scores of ≥10 (8.3 v 6.4 months, 0.58, 0.45 to 0.75, P<0.001). Adverse events related to treatment occurred in 321 of 327 patients (98%) in the sintilimab-chemotherapy group versus 326 of 332 (98%) patients in the placebo-chemotherapy group. Rates of adverse events related to treatment, grade ≥3, were 60% (196/327) and 55% (181/332) in the sintilimab-chemotherapy and placebo-chemotherapy groups, respectively.ConclusionsCompared with placebo, sintilimab in combination with cisplatin plus paclitaxel showed significant benefits in overall survival and progression free survival as first line treatment in patients with advanced or metastatic oesophageal squamous cell carcinoma. Similar benefits of sintilimab with cisplatin plus 5-fluorouracil seem promising.Trial registrationClinicalTrials.gov NCT03748134.

2.
Environmental Research ; 212:113297, 2022.
Article in English | ScienceDirect | ID: covidwho-1796872

ABSTRACT

Meteorological factors have been confirmed to affect the COVID-19 transmission, but current studied conclusions varied greatly. The underlying causes of the variance remain unclear. Here, we proposed two scientific questions: (1) whether meteorological factors have a consistent influence on virus transmission after combining all the data from the studies;(2) whether the impact of meteorological factors on the COVID-19 transmission can be influenced by season, geospatial scale and latitude. We employed a meta-analysis to address these two questions using results from 2813 published articles. Our results showed that, the influence of meteorological factors on the newly-confirmed COVID-19 cases varied greatly among existing studies, and no consistent conclusion can be drawn. After grouping outbreak time into cold and warm seasons, we found daily maximum and daily minimum temperatures have significant positive influences on the newly-confirmed COVID-19 cases in cold season, while significant negative influences in warm season. After dividing the scope of the outbreak into national and urban scales, relative humidity significantly inhibited the COVID-19 transmission at the national scale, but no effect on the urban scale. The negative impact of relative humidity, and the positive impacts of maximum temperatures and wind speed on the newly-confirmed COVID-19 cases increased with latitude. The relationship of maximum and minimum temperatures with the newly-confirmed COVID-19 cases were more susceptible to season, while relative humidity's relationship was more affected by latitude and geospatial scale. Our results suggested that relationship between meteorological factors and the COVID-19 transmission can be affected by season, geospatial scale and latitude. A rise in temperature would promote virus transmission in cold seasons. We suggested that the formulation and implementation of epidemic prevention and control should mainly refer to studies at the urban scale. The control measures should be developed according to local meteorological properties for individual city.

3.
Journal of Hazardous Materials ; : 128980, 2022.
Article in English | ScienceDirect | ID: covidwho-1796501

ABSTRACT

The ingestion and accumulation of microplastics is a serious threat to the health and survival of humans and other organisms given the increasing use of daily-use plastic products, especially during the COVID-19 pandemic. However, whether direct microplastic contamination from plastic packaging is a threat to human health remains unclear. We analyzed the market demand for plastic packaging in Asia-Pacific, North America, and Europe and identified the commonly used plastic food packaging products. We found that food containers exposed to high-temperature water release more than 10 million microplastics per mL of water. Recycled plastic food packaging was demonstrated to continuously leach micro- and nanoplastics. In vitro cell engulfing experiments revealed that these leachates are readily taken up by murine macrophages without any conditioning and that short-term exposure substantially suppressed the lysosomal activities of macrophages. We demonstrated that the ingestion of micro- and nanoplastics released from food containers exerts immediate negative effects on macrophage activities, proving that the explosive growth in the use of plastic packaging poses severe health risks.

4.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-333130

ABSTRACT

Background: The epidemiological characteristics and transmissibility of Coronavirus Disease 2019 (COVID-19) may undergo changes due to the mutation of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) strains. The purpose of this study is to compare the differences in the outbreaks of the different strains, with regards to aspects such as epidemiological characteristics, transmissibility, and difficulties in prevention and control. Methods: COVID-19 data from outbreaks of pre-Delta strains, the Delta variant and Omicron variant, were obtained from the Chinese Center for Disease Control and Prevention (CDC). Case data were collected from China’s direct-reporting system, and the data concerning outbreaks were collected by on-site epidemiological investigators and collated by the authors of this paper. Indicators such as the effective reproduction number (Reff), time-dependent reproduction number (Rt), rate of decrease in transmissibility (RDT), and duration from the illness onset date to the diagnosed date (DID) / reported date (DIR) were used to compare differences in transmissibility between pre-Delta strains, Delta variants and Omicron variants. A nonparametric test was used to compare differences in epidemiological characteristics and transmissibility between outbreaks of different strains. P < 0.05 indicated that the difference was statistically significant. Results: Mainland China has maintained a “dynamic zero-out strategy” since the first case was reported, and clusters of outbreaks have occurred intermittently. The strains causing outbreaks in mainland China have gone through three stages: the outbreak of pre-Delta strains, the outbreak of the Delta variant, and outbreaks involving the superposition of Delta and Omicron variant strains. Each outbreak of pre-Delta strains went through two stages: a rising stage and a falling stage;Each outbreak of the Delta variant and Omicron variant went through three stages: a rising stage, a platform stage and a falling stage. The maximum Reff value of Omicron variant outbreaks was highest (median: 6.7;ranged from 5.3 to 8.0) and the differences were statistically significant. The RDT value of outbreaks involving pre-Delta strains was smallest (median: 91.4%;[IQR]: 87.30%-94.27%), and the differences were statistically significant. The DID and DIR of all strains accounted for the most in 0 ~ 2 days, with more than 75%. The range of duration for outbreaks of pre-Delta strains was the largest (median: 20 days, ranging from 1 to 61 days), and the differences were statistically significant. Conclusion: With the evolution of the virus, the transmissibility of the variants has increased. The transmissibility of the Omicron variant is higher than that of both the pre-Delta strains and the Delta variant, and is more difficult to suppress. These findings enable us to get a more clear and precise picture of the transmissibility of the different variants in the real world, in accordance with the findings of previous studies. Reff is more suitable than Rt for assessing the transmissibility of the disease during an epidemic outbreak.

5.
Med Phys ; 2022 Apr 09.
Article in English | MEDLINE | ID: covidwho-1782646

ABSTRACT

PURPOSE: COVID-19 has become a global pandemic and is still posing a severe health risk to the public. Accurate and efficient segmentation of pneumonia lesions in CT scans is vital for treatment decision-making. We proposed a novel unsupervised approach using cycle consistent generative adversarial network (cycle-GAN) which automates and accelerates the process of lesion delineation. METHOD: The workflow includes lung volume segmentation, healthy lung image synthesis, infected and healthy image subtraction, and binary lesion mask creation. The lung volume was first delineated using a pre-trained U-net and worked as the input for the following network. A cycle-GAN was developed to generate synthetic healthy lung CT images from infected lung images. After that, the pneumonia lesions are extracted by subtracting the synthetic healthy lung CT images from the infected lung CT images. A median filter and K-means clustering were then applied to contour the lesions. The auto segmentation approach was validated on three different datasets. RESULTS: The average Dice coefficient reached 0.666±0.178 on the three datasets. Especially, the dice reached 0.748±0.121 and 0.730±0.095, respectively, on two public datasets Coronacases and Radiopedia. Meanwhile, the average precision and sensitivity for lesion segmentation on the three datasets were 0.679±0.244 and 0.756±0.162. The performance is comparable to existing supervised segmentation networks and outperforms unsupervised ones. CONCLUSION: The proposed label-free segmentation method achieved high accuracy and efficiency in automatic COVID-19 lesion delineation. The segmentation result can serve as a baseline for further manual modification and a quality assurance tool for lesion diagnosis. Furthermore, due to its unsupervised nature, the result is not influenced by physicians' experience which otherwise is crucial for supervised methods. This article is protected by copyright. All rights reserved.

6.
Res Sq ; 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1786457

ABSTRACT

The SARS-CoV-2 RNA genome contains a 5'-cap that facilitates translation of viral proteins, protection from exonucleases and evasion of the host immune response1-4. How this cap is made is not completely understood. Here, we reconstitute the SARS-CoV-2 7MeGpppA2'-O-Me-RNA cap using virally encoded non-structural proteins (nsps). We show that the kinase-like NiRAN domain5 of nsp12 transfers RNA to the amino terminus of nsp9, forming a covalent RNA-protein intermediate (a process termed RNAylation). Subsequently, the NiRAN domain transfers RNA to GDP, forming the cap core structure GpppA-RNA. The nsp146 and nsp167 methyltransferases then add methyl groups to form functional cap structures. Structural analyses of the replication-transcription complex bound to nsp9 identified key interactions that mediate the capping reaction. Furthermore, we demonstrate in a reverse genetics system8 that the N-terminus of nsp9 and the kinase-like active site residues in the NiRAN domain are required for successful SARS-CoV-2 replication. Collectively, our results reveal an unconventional mechanism by which SARS-CoV-2 caps its RNA genome, thus exposing a new target in the development of antivirals to treat COVID-19.

7.
Front Immunol ; 13: 770982, 2022.
Article in English | MEDLINE | ID: covidwho-1775662

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike protein (S) of SARS-CoV-2 is a major target for diagnosis and vaccine development because of its essential role in viral infection and host immunity. Currently, time-dependent responses of humoral immune system against various S protein epitopes are poorly understood. In this study, enzyme-linked immunosorbent assay (ELISA), peptide microarray, and antibody binding epitope mapping (AbMap) techniques were used to systematically analyze the dynamic changes of humoral immune responses against the S protein in a small cohort of moderate COVID-19 patients who were hospitalized for approximately two months after symptom onset. Recombinant truncated S proteins, target S peptides, and random peptides were used as antigens in the analyses. The assays demonstrated the dynamic IgM- and IgG recognition and reactivity against various S protein epitopes with patient-dependent patterns. Comprehensive analysis of epitope distribution along the spike gene sequence and spatial structure of the homotrimer S protein demonstrated that most IgM- and IgG-reactive peptides were clustered into similar genomic regions and were located at accessible domains. Seven S peptides were generally recognized by IgG antibodies derived from serum samples of all COVID-19 patients. The dynamic immune recognition signals from these seven S peptides were comparable to those of the entire S protein or truncated S1 protein. This suggested that the humoral immune system recognized few conserved S protein epitopes in most COVID-19 patients during the entire duration of humoral immune response after symptom onset. Furthermore, in this cohort, individual patients demonstrated stable immune recognition to certain S protein epitopes throughout their hospitalization period. Therefore, the dynamic characteristics of humoral immune responses to S protein have provided valuable information for accurate diagnosis and immunotherapy of COVID-19 patients.


Subject(s)
COVID-19 , Antibodies, Viral , Epitopes , Humans , Immunity, Humoral , Immunoglobulin G , Immunoglobulin M , Peptides , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
8.
Front Public Health ; 9: 665985, 2021.
Article in English | MEDLINE | ID: covidwho-1771100

ABSTRACT

Purpose: This study examined the association between storey of building and fall risk in older adults' residences and residents' level of fear of falling. Methods: The National Health and Ageing Trends Study (NHATS) collected information that would provide an understanding of basic trends people aged 65 years and older. Using a longitudinal survey, the present study employed the first round of NHATS data that was collected in 2011. In the first round, 12,411 participants were enrolled, and 8,077 interviews were completed. The study sample sizes for falling and worry about falling are 6,153 and 6,142, respectively. Results: Unadjusted analysis revealed that storey of building was a risk factor for fall and worry about falling. There was a higher prevalence for fall and worry about falling when subjects lived in single storey of building compared with the subjects live in multi-storey. Logistic regression analysis showed no highly significant between storey of building and the fall/fear of falling. Conclusion: Several clinical factors independently were indicated pertaining to the fall and worry about falling in older adult's residences.


Subject(s)
Accidental Falls , Aged , Aging , Fear , Humans , Risk Factors
9.
Vaccines ; 10(4):496, 2022.
Article in English | MDPI | ID: covidwho-1762227

ABSTRACT

Omicron, the latest SARS-CoV-2 Variant of Concern (VOC), first appeared in Africa in November 2021. At present, the question of whether a new VOC will out-compete the currently predominant variant is important for governments seeking to determine if current surveillance strategies and responses are appropriate and reasonable. Based on both virus genomes and daily-confirmed cases, we compare the additive differences in growth rates and reproductive numbers (R0) between VOCs and their predominant variants through a Bayesian framework and phylo-dynamics analysis. Faced with different variants, we evaluate the effects of current policies and vaccinations against VOCs and predominant variants. The model also predicts the date on which a VOC may become dominant based on simulation and real data in the early stage. The results suggest that the overall additive difference in growth rates of B.1.617.2 and predominant variants was 0.44 (95% confidence interval, 95% CI: −0.38, 1.25) in February 2021, and that the VOC had a relatively high R0. The additive difference in the growth rate of BA.1 in the United Kingdom was 6.82 times the difference between Delta and Alpha, and the model successfully predicted the dominating process of Alpha, Delta and Omicron. Current vaccination strategies remain similarly effective against Delta compared to the previous variants. Our model proposes a reliable Bayesian framework to predict the spread trends of VOCs based on early-stage data, and evaluates the effects of public health policies, which may help us better prepare for the upcoming Omicron variant, which is now spreading at an unprecedented speed.

10.
Iran J Public Health ; 50(8): 1517-1525, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1761438

ABSTRACT

Background: COVID-19 has resulted in an emerging respiratory infection with a pandemical diffusion since December 2019. We aimed to elucidate whether the presence of thyroid disease might increase the risk of severe COVID-19 infection. Methods: Studies reporting seriously ill in COVID-19 patients with and without thyroid disease combined were searched and 11 relevant studies were subjected to our analysis, and pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated by using STATA and Review Manager Software. Results: In total, 2,995 COVID-19 patients were included in this study. The pooled ORs were calculated using a fixed-effects model according to the heterogeneity. The pooled results revealed that thyroid disease was associated with severe COVID-19 infection in patients (OR = 2.14, 95 % CI: 1.23-3.72, P = 0.007). In the subgroup analysis by type of thyroid disease, hypothyroidism was positively associated with risks of severe COVID-19 infection (OR = 4.78, 95 % CI: 1.59-14.36, P = 0.005), however, no obvious difference was found in the risk regarding the severe COVID-19 infection amongst hyperthyroidism or unclassified thyroid disease. In addition, subgroup analysis stratified by ethnic groups demonstrated that thyroid disease was linked to the risks of severe COVID-19 infection in Asian patients (OR = 2.41, 95 % CI: 1.30-4.48, P = 0.005) rather than non-Asian (OR = 1.31, 95 % CI: 0.35-4.87, P = 0.684). Conclusion: This study indicates a correlation between thyroid disease and severe COVID-19 infection.

12.
Journal of Shandong University ; 59(2):88-94, 2021.
Article in Chinese | GIM | ID: covidwho-1744693

ABSTRACT

Objective: To explore the chain mediating effect of perceived social support and coping strategies on resilience and compassion fatigue of first-line nurses treating patients with COVID-19.

13.
PLoS One ; 17(3): e0265117, 2022.
Article in English | MEDLINE | ID: covidwho-1742021

ABSTRACT

BACKGROUND: To investigate the mortality and health care resource use among patients with severe or critical coronavirus disease of 2019 (COVID-19) in the first wave of pandemic in China. METHODS: We performed a systematic review and meta-analysis to investigate the mortality, discharge rate, length of hospital stay, and use of invasive ventilation in severe or critical COVID-19 cases in China. We searched electronic databases for studies from China with no restrictions on language or interventions patients received. We screened records, extracted data and assessed the quality of included studies in duplicate. We performed the meta-analysis using random-effect models through a Bayesian framework. Subgroup analyses were conducted to examine studies by disease severity, study location and patient enrolment start date. We also performed sensitivity analysis using various priors, and assessed between-study heterogeneity and publication bias for the primary outcomes. RESULTS: Out of 6,205 titles and abstracts screened, 500 were reviewed in full text. A total of 42 studies were included in the review, of which 95% were observational studies (n = 40). The pooled 28-day and 14-day mortalities among severe or critical patients were 20.48% (7,136 patients, 95% credible interval (CrI), 13.11 to 30.70) and 10.83% (95% CrI, 6.78 to 16.75), respectively. The mortality declined over time and was higher in patients with critical disease than severe cases (1,235 patients, 45.73%, 95% CrI, 22.79 to 73.52 vs. 3,969 patients, 14.90%, 95% CrI, 4.70 to 39.57) and patients in Hubei compared to those outside Hubei (6,719 patients, 26.62%, 95% CrI, 13.11 to 30.70 vs. 244 patients, 5.88%, 95% CrI 2.03 to 14.11). The length of hospital stay was estimated at 18.48 days (6,847 patients, 95% CrI, 17.59 to 21.21), the 28-day discharge rate was 50.48% (3,645 patients, 95% CrI, 26.47 to 79.53), and the use of invasive ventilation rate was 13.46% (4,108 patients, 95% CrI, 7.61 to 22.31). CONCLUSIONS: Our systematic review and meta-analysis found high mortality among severe and critical COVID-19 cases. Severe or critical COVID-19 cases consumed a large amount of hospital resources during the outbreak.


Subject(s)
COVID-19 , Critical Care , Length of Stay , Pandemics , SARS-CoV-2 , COVID-19/mortality , COVID-19/therapy , China/epidemiology , Critical Illness , Humans , Severity of Illness Index
14.
BMC Psychiatry Vol 22 2022, ArtID 33 ; 22, 2022.
Article in English | APA PsycInfo | ID: covidwho-1738252

ABSTRACT

Background: A global public health emergency triggered by the Coronavirus Disease 2019 (COVID-19) epidemic may have are markable psychological impact on the population. There is still limited psychological research on police officers, especially prison officers in the process of enforcing the law. The present study aims to identify prevalence and influencing factors on mental health status among frontline prison officers in China during the prevention and control of the COVID-19 epidemic. Methods: A cross-sectional survey with a sample of 981 frontline prison officers was conducted using snowball sampling approach. The self-administered questionnaire consisted of 4 parts: (i) informed consent form;(ii) socio-demographic section;(iii) work and life situations during the prevention and control of the COVID-19 epidemic;(iv) the Chinese version of the 12-item General Health Questionnaire (GHQ-12). Univariate analysis and multivariable logistic regression were performed to identify factors influencing mental health status. Results: The prevalence of being prone to mental health problems (GHQ-12 score >= 4) was 33.43% among frontline prison officers. The results of GHQ-12 factors analysis indicated that the prison officers suffered from psychological issues was related to anxiety and depression, which main symptoms were unhappy and depressed, lost sleep over worry and constantly under strain. Multivariate logistic regression analysis revealed that male (OR = 1.573, 95% CI:1.385-1.853), lockdown shift inside the prison(OR = 2.203, 95% CI:2.139-2.297), more night shifts (OR = 2.163, 95% CI:2.031-2.317;OR = 2.749, 95% CI:2.194-2.901), more smoking (OR = 1.100, 95% CI:1.037-2.168), poor self-reported physical condition (OR = 1.947, 95% CI:1.478-2.250), chronic or serious illness history(OR = 1.870, 95% CI:1.314-2.660;OR = 2.214, 95% CI:1.460-2.812) were risk factors for mental health among frontline prison officers, while regular diet (OR = 0.779, 95% CI:0.539-0.928), more physical exercise (OR = 0.702, 95% CI:0.548-0.899;OR = 0.641, 95% CI:0.316-0.887), more communication with family members (OR = 0.437, 95% CI:0.295-0.616) were protective factors. Conclusion: Chinese frontline prison officers experienced different psychological stress coming from the prevention and control of this epidemic. Therefore, continued surveillance of psychological problems and targeted mental health care for frontline prison officers were urgent. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

15.
Emerg Microbes Infect ; 11(1): 902-913, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1730557

ABSTRACT

The immune memory of over 400 million COVID-19 convalescents is not completely understood. In this integrated study, we recorded the post-acute sequelae symptoms and tested the immune memories, including circulating antibodies, memory B cell, and memory CD4 or CD8 T cell responses of a cohort of 65 COVID-19 patients over 1-year after infection. Our data show that 48% of them still have one or more sequelae symptoms and all of them maintain at least one of the immune components. The chances of having sequelae symptoms or having better immune memory are associated with peak disease severity. We did four-time points sampling per subject to precisely understand the kinetics of durability of SARS-CoV-2 circulating antibodies. We found that the RBD IgG levels likely reach a stable plateau at around 6 months, albeit it is waning at the first 6 months after infection. At 1-year after infection, more than 90% of the convalescents generated memory CD4 or CD8 T memory responses, preferably against the SARS-CoV-2 M peptide pool. The convalescents also have polyfunctional and central memory T cells that could provide rapid and efficient response to SARS-CoV-2 re-infection. Based on this information, we assessed the immune protection against the Omicron variant and concluded that convalescents should still induce effective T cell immunity against the Omicron. By studying the circulating antibodies and memory B or T cell responses to SARS-CoV-2 in an integrated manner, our study provides insight into the understanding of protective immunity against diseases caused by secondary SARS-CoV-2 infection.


Subject(s)
COVID-19 , Antibodies, Viral , Humans , Immunity, Cellular , Longitudinal Studies , SARS-CoV-2
16.
Mol Divers ; 2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1729341

ABSTRACT

Xuanbai Chengqi Decoction (XBCQD), a classic traditional Chinese medicine, has been widely used to treat COVID-19 in China with remarkable curative effect. However, the chemical composition and potential therapeutic mechanism is still unknown. Here, we used multiple open-source databases and literature mining to select compounds and potential targets for XBCQD. The COVID-19 related targets were collected from GeneCards and NCBI gene databases. After identifying putative targets of XBCQD for the treatment of COVID-19, PPI network was constructed by STRING database. The hub targets were extracted by Cytoscape 3.7.2 and MCODE analysis was carried out to extract modules in the PPI network. R 3.6.3 was used for GO enrichment and KEGG pathway analysis. The effective compounds were obtained via network pharmacology and bioinformatics analysis. Drug-likeness analysis and ADMET assessments were performed to select core compounds. Moreover, interactions between core compounds and hub targets were investigated through molecular docking, molecular dynamic (MD) simulations and MM-PBSA calculations. As a result, we collected 638 targets from 61 compounds of XBCQD and 845 COVID-19 related targets, of which 79 were putative targets. Based on the bioinformatics analysis, 10 core compounds and 34 hub targets of XBCQD for the treatment of COVID-19 were successfully screened. The enrichment analysis of GO and KEGG indicated that XBCQD mainly exerted therapeutic effects on COVID-19 by regulating signal pathways related to viral infection and inflammatory response. Meanwhile, the results of molecular docking showed that there was a stable binding between the core compounds and hub targets. Moreover, MD simulations and MM-PBSA analyses revealed that these compounds exhibited stable conformations and interacted well with hub targets during the simulations. In conclusion, our research comprehensively explained the multi-component, multi-target, and multi-pathway intervention mechanism of XBCQD in the treatment of COVID-19, which provided evidence and new insights for further research.

17.
Chem Eng J ; 438: 135589, 2022 Jun 15.
Article in English | MEDLINE | ID: covidwho-1712496

ABSTRACT

Nearly 200 million people have been diagnosed with COVID-19 since the outbreak in 2019, and this disease has claimed more than 5 million lives worldwide. Currently, researchers are focusing on vaccine development and the search for an effective strategy to control the infection source. This work designed a detection platform based on Surface-Enhanced Raman Spectroscopy (SERS) by introducing acetonitrile and calcium ions into the silver nanoparticle reinforced substrate system to realize the rapid detection of novel coronavirus. Acetonitrile may amplify the calcium-induced hot spots of silver nanoparticles and significantly enhanced the stability of silver nanoparticles. It also elicited highly sensitive SERS signals of the virus. This approach allowed us to capture the characteristic SERS signals of SARS-CoV-2, Human Adenovirus 3, and H1N1 influenza virus molecules at a concentration of 100 copies/test (PFU/test) with upstanding reproduction and signal-to-noise ratio. Machine learning recognition technology was employed to qualitatively distinguish the three virus molecules with 1000 groups of spectra of each virus. Acetonitrile is a potent internal marker in regulating the signal intensity of virus molecules in saliva and serum. Thus, we used the SERS peak intensity to quantify the virus content in saliva and serum. The results demonstrated a satisfactory linear relationship between peak intensity and protein concentration. Collectively, this rapid detection method has a broad application prospect in clinical diagnosis of viruses, management of emergent viral infectious diseases, and exploration of the interaction between viruses and host cells.

18.
STAR Protoc ; 3(2): 101238, 2022 06 17.
Article in English | MEDLINE | ID: covidwho-1704569

ABSTRACT

The immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteome is largely unknown. Here we describe a protocol for analyzing sera samples with SARS-CoV-2 proteome microarray. The proteins were expressed by either E. coli expression system or eukaryotic cell expression systems and obtained by affinity purification. The protocol includes microarray fabricating and sera profiling, which will be used to build an antibody response landscape for IgG and IgM. The protocol may help to facilitate a deeper understanding of immunity related to SARS-CoV-2. For complete details on the use and execution of this protocol, please refer to Li et al. (2021c).


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Escherichia coli , Humans , Proteome
19.
J Mater Chem B ; 10(6): 870-879, 2022 Feb 09.
Article in English | MEDLINE | ID: covidwho-1704333

ABSTRACT

In this study, we developed a crystal-reconstructed-BiVO4 aptamer photoelectrochemical (PEC) biosensor by a high-energy laser treatment technique. This biosensor achieves a limit of detection (LOD) (0.82 ag mL-1), linear detection range (1 ag mL-1 to 2 ng mL-1), and resolution ratio (∼18 molecules per mL) for prostate-specific antigen (PSA) tumor biomarker detection. Furthermore, reconstructed surface microstructure and oxygen vacancy doping energy formation after crystal reconstruction induce the stereo-hindrance effect and photogenerated hole energy is reduced during PSA target detection. In this case, a photocurrent inhibition phenomenon for PSA detection is noticed. Based on this photocurrent inversion phenomenon, some dysoxidizable nucleonic acid tumor (miRNA-21) and virus biomarkers (RdRp-COVID) can be detected with a LOD level of ∼10-16 M by linking the corresponding base paring probe on the surface of the crystal-reconstructed photoanode. In addition to high sensitivity, this PEC biosensor presents high detection specificity, stability, and accuracy in clinical verification. Thus, this crystal-reconstructed PEC biosensor shows application potential in the fields of multi-tumor or viral biomarker detection.

20.
Arch Virol ; 167(4): 1125-1130, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1694546

ABSTRACT

Given the structural similarities of the viral enzymes of different coronaviruses (CoVs), we investigated the potency of the anti-SARS-CoV-2 agents boceprevir and GC376 for counteracting seasonal coronavirus infections. In contrast to previous findings that both boceprevir and GC376 are potent inhibitors of the main protease (Mpro) of SARS-CoV-2, we found that GC376 is much more effective than boceprevir in inhibiting SARS-CoV-2 and three seasonal CoVs (NL63, 229E, and OC43) in cell culture models. However, these results are discordant with a molecular docking analysis that suggested comparable affinity of boceprevir and GC376 for the different Mpro enzymes of the four CoVs. Collectively, our results support future development of GC376 but not boceprevir (although it is an FDA-approved antiviral medication) as a pan-coronavirus antiviral agent. Furthermore, we caution against overinterpretation of in silico data when developing antiviral therapies.


Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Humans , Molecular Docking Simulation , Proline/analogs & derivatives , Protease Inhibitors/pharmacology , Pyrrolidines , SARS-CoV-2 , Sulfonic Acids
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