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2.
China Oncology ; 32(6):499-511, 2022.
Article in Chinese | Scopus | ID: covidwho-1964893

ABSTRACT

[] The corona virus disease 2019 (COVID-19) pandemic continues to severely impact healthcare systems around the world, and patients with cancer are even worse affected owing to compromised immune status and greater exposure risk. In the present review, we retrieved the relevant literature including guidelines and consensuses directly related to the purpose of this study from the PubMed database, and then summarized the research data on cancer and COVID-19, aiming to discuss the personal protection, systemic anti-cancer therapy, outcome of co-infection, and the clinical management strategy in this population. We found that patients with malignant tumors had a higher chance of suffering COVID-19, co-infection of whom had an even worse clinical prognosis, especially for those with lung cancer or hematologic cancers. Systemic chemotherapy may delay the clearance of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) virus of human body, and thus have a negative impact on the clinical outcomes of COVID-19, while certain endocrine therapy and targeted drugs having limited or no impact. There has been no sufficient evidence for the impact of immune checkpoint therapy on the outcomes of COVID-19 till now. It is of great value to strengthen the personal protection of patients, adjust the anti-tumor treatments rationally and optimize the clinical management processes. © 2022, Editorial Office of China Oncology. All rights reserved.

3.
Bull Exp Biol Med ; 172(6): 721-724, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1942032

ABSTRACT

This study was intended to define T lymphocyte subsets in different clinical groups of COVID-19-infected patients to explore the interaction between T cell-mediated immune response and the severity of COVID-19 course. Lymphopenia in patients with severe COVID-19 was found. In patients with severe COVID-19 course, the absolute counts of CD3+, CD4+, and CD8+ T lymphocytes at admission were lower than on day 14 after discharge. Further analysis showed that the older were the patients with COVID-19, the more likely they developed severe infection. The results confirmed the significance of T lymphocytes in the clearance of the COVID-19.


Subject(s)
COVID-19 , CD8-Positive T-Lymphocytes , Humans , Lymphocyte Count , Lymphocyte Subsets , T-Lymphocyte Subsets
4.
Atmosphere ; 13(5), 2022.
Article in English | Scopus | ID: covidwho-1933965

ABSTRACT

Mass suspension of anthropogenic activities is extremely rare, the quarantine due to the coronavirus disease 2019 (COVID-19) represents a natural experiment to investigate the impact of anthropogenic activities on air quality. The mitigation of air pollution during the COVID-19 lock-down has been reported from a global perspective;however, the air pollution levels vary in different regions. This study initiated a novel synthesis of multiple-year satellite observations, national ground measurements towards SO2, NO2 and O3 and meteorological conditions to evaluate the impact of the COVID-19 lockdown in Beihai, a specific city in a less developed area in southwest China, to reveal the potential implications of control strategies for air pollution. The levels of the major air pollutants during the COVID-19 lockdown (LP) and during the same period of previous years (SP) were compared and a series of statistical tools were applied to analyze the sources of air pollution in Beihai. The results show that air pollutant levels decreased with substantial diversity during the LP. Satellite-retrieved NO2 and SO2 levels during the LP decreased by 5.26% and 22.06%, while NO2, SO2, PM2.5 and PM10 from ground measurements during the LP were 25.6%, 2.7%, 22.2% and 22.2% lower than during SP, respectively. Ground measured SO2 concentrations during the LP were only 2.7% lower than during the SP, which may be attributed to uninterrupted essential industrial activ-ities, such as power plants. Polar plots analysis shows that NO2 concentrations were strongly associated with local emission sources, such as automobiles and local industry. Additionally, the much lower levels of NO2 concentrations during the LP and the absence of an evening peak may highlight the significant impact of the traffic sector on NO2. The decrease in daily mean O3 concentrations during the LP may be associated with the reduction in NO2 concentrations. Indications in this study could be beneficial for the formulation of atmospheric protection policies. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

5.
Chinese Journal of Microbiology and Immunology (China) ; 42(4):245-250, 2022.
Article in Chinese | EMBASE | ID: covidwho-1928717

ABSTRACT

Objective To analyze the genome characteristics and variations in nucleotides and amino acids of SARS-CoV-2 causing an outbreak in Henan Province in November 2021 and perform the traceability analysis.Methods In this study, throat swab specimens from cases in the acute phase were collected and tested for the nucleic acids of SARS-CoV-2 by real-time fluorescent RT-PCR.SARS-CoV-2 nucleic acid-positive samples were subjected to high-throughput genome sequencing and whole-genome alignment analysis.Results The median Ct values of ORF1ab gene and N gene in 70 positive specimens was 26.41 (15.58 to 39.27) and 24.43 (12.04 to 39.74), respectively.Compared with the sequence of Wuhan-Hu(NC_045512) reference strain, 47 to 49 nucleotide mutations sharing 47 nucleotide mutation and 41 amino acid mutations were found in 63 strains of successfully sequenced SARS-CoV-2.Nine nucleotide mutations and 12 amino acid mutations were found in the spike protein.The index case shared 47 mutations with the Russian imported cases in Henan Province on October 14 and the local cases in Jiangxi Province in October.Moreover, their genomes were highly homologous and they all belonged to the Delta variant (AY.122 evolutionary branch).Conclusions Continuous monitoring of imported COVID-19 cases and prolonging the period of quarantine were needed to reduce the risk of local outbreak and epidemic caused by imported COVID-19 cases.Analysis of the genomic characteristics of SARS-CoV-2 and the variations in nucleotides and amino acids was conducive to trace the origin of COVID-19 outbreak quickly and provide reference for precise control.

6.
Chinese Journal of Microbiology and Immunology (China) ; 42(1):16-22, 2022.
Article in Chinese | EMBASE | ID: covidwho-1928714

ABSTRACT

Objective To detect the serum levels of SARS-CoV-2-specific IgM and IgG antibodies in patients infected with SARS-CoV-2 and recipients of inactivated vaccine in different periods for understanding their variation patterns in vivo. Methods Chemiluminescence immunoassay was used to detect the levels of SARS-CoV-2-specific IgM and IgG antibodies in 144 serum samples of 44 COVID-19 patients, 381 serum samples of 118 asymptomatic infected cases and 398 serum samples of 273 inactivated vaccine recipients collected at different periods. The results were statistically analyzed together with basic characteristics and vaccination status. Results The positive rates of IgM antibody in COVID-19 patients, asymptomatic infected cases and inactivated vaccine recipients were 52. 27% (23 / 44), 23. 73% (28 / 118) and 14. 29% (39 / 273). The positive rate of IgM antibody was higher in COVID-19 patients than in asymptomatic infected cases and vaccine recipients (χ2 = 12. 106, P = 0. 001;χ2 = 34. 755, P<0. 001). The positive rates of IgG antibody in the three populations were 100. 00% (44 / 44), 97. 46% (115 / 118) and 98. 81% (166 / 168), and the differences were not statistically significant (χ2 = 2. 944, P = 0. 229). In COVID-19 patients, the concentration of IgM antibody in <40 years old group was lower than that in ≥40 years old group (Waldχ2 = 6. 609, P = 0. 010), and the concentration of IgG antibody in patients with vaccination was higher than that in patients without vaccination (Waldχ2 = 12. 402,P<0. 001). In asymptomatic infected cases, the concentration of IgG antibody was higher in people with vaccination than in those without vaccination (Waldχ2 = 4. 530, P = 0. 033). In SARS-CoV-2 vaccine recipients, the concentration of IgG antibody in <40 years old group was higher than that in ≥40 years old group (Waldχ2 = 9. 565, P = 0. 002). Dynamic analysis of antibody levels showed that from week 1 to week 9, the concentrations of IgM and IgG antibodies in COVID-19 patients were higher than those in asymptomatic infected cases and vaccine recipients. Conclusions The concentrations of IgM and IgG antibodies in COVID-19 patients were higher than those in asymptomatic infected cases and inactivated vaccine recipients. COVID-19 patients aged ≥40 years had higher level of IgM antibody. COVID-19 patients and asymptomatic infected cases who had received vaccination had higher concentration of IgG antibody. Inactivated vaccine showed good immunogenicity after whole course of immunization, and the IgG antibody level in <40 years old group was higher.

7.
Chinese Pharmaceutical Journal ; 57(10):845-850, 2022.
Article in Chinese | EMBASE | ID: covidwho-1918126

ABSTRACT

OBJECTIVE: To review the mechanism and the clinical research progress of nirmatrelvir tablets/ritonavir tablets(PaxlovidTM), so as to provide references for its rational usage. METHODS: Literatures related to nirmatrelvir tablets/ritonavir tablets in the official website of US Food and Drug Administration, Pubmed, Embase, CNKI, CBM and Wanfang were systematically searched. The basic information, mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy evaluation, safety, drug interaction, drug use in special populations were reviewed. RESULTS AND CONCLUSIONS: Nirmatrelvir tablets/ritonavir tablets inhibit the replication of SARS-COV-2 virus by inhibiting the processing of SARS-CoV-2 protein precursor mediated by the main protease. Based on current trial results, nirmatrelvir tablets/ritonavir tablets can significantly reduce hospitalization and mortality rates in adult patients with mild and moderate COVID-19. More research is required to determine whether the drug is appropriate for the clinical treatment of all COVID-19 patients.

8.
Global Advances in Health and Medicine ; 11:47, 2022.
Article in English | EMBASE | ID: covidwho-1916546

ABSTRACT

Methods: The survey was designed by an international team, translated and adapted to simplified Chinese, including 132 kinds of traditional Chinese medicine (TCM) preparation recommended by guidelines. It was distributed and collected from February to May 2021, with data analysed by WPS spreadsheet and wjx.cn. Descriptive statistics were used to describe demographics and clinical characteristics, diagnosis, treatments, preventative behaviours and interventions, and their associated outcomes. Results: The survey was accessed 503 times with 341 (67.8%) completions covering 23 provinces and four municipalities in China. Most (282/341, 82.7%) respondents reported no symptoms during the pandemic and the majority (290/341, 85.0%) reported having a SARS-CoV-2 PCR test at some point. Forty-five (13.2%) reported having a respiratory infection, among which 19 (42.2%) took one or more categories of modern medicine, e.g. painkillers, antibiotics;16 (35.6%) used TCM interventions(s);while seven respondents combined TCM with modern medicine. All respondents reported using at least one behavioural or medical approach to prevention, with 22.3% taking TCM and 5.3% taking modern medicines. No respondents reported having a critical condition related to COVID-19. Background: We aimed to investigate use of infection control behaviours, preventative and therapeutic interventions, and outcomes among respondents to an online survey during the COVID-19 pandemic in China. Conclusion: We found evidence of widespread use of infection control behaviours, modern medicines and TCM for treatment and prevention of COVID-19 and other respiratory symptoms. Larger scale studies are warranted, including a more representative sample exploring TCM preparations recommended in clinical guidelines.

9.
Engineering, Construction and Architectural Management ; 2022.
Article in English | Scopus | ID: covidwho-1891304

ABSTRACT

Purpose: The impacts of COVID-19 on construction projects have attracted much attention in the construction management research community. Nevertheless, a systematic review of these studies is still lacking. The purpose of this paper is to systematically analyze the impacts of COVID-19 on the different stages of a project life-cycle, and comprehensively sort out the epidemic response measures adopted by project participants. In addition, the study also attempts to explore the challenges and opportunities faced by project management practitioners under the context of COVID-19. Design/methodology/approach: This study comprehensively demonstrates the systematic review process of COVID-19 related research in the construction industry, systematically summarizes the research status of the impact of COVID-19 on construction projects, and defines the strategies to deal with COVID-19 in project management;and through the visualization research, determines the current key research topics and future research trends. Findings: This study identifies 11 construction activities in the project management life cycle that are affected by COVID-19 and finds that the COVID-19 epidemic has the greatest impact on construction workers, construction standards, construction contracts and construction performance. The study further summarizes the six main epidemic countermeasures and mitigation measures taken within the construction industry following the arrival of the epidemic. In addition, the results of this study identify opportunities and future trends in intelligent construction technology, rapid manufacturing engineering and project management in the construction industry in the post-epidemic era through literature results, which also provide ideas for related research. Practical implications: COVID-19 has brought severe challenges to society. It is of great significance for the future sustainable development of the construction industry to identify the impact of COVID-19 on all phases of the project and to promote the development of coping strategies by project stakeholders. Originality/value: First of all, there is little study comprehensively reviewing the impacts of COVID-19 on the different stages of construction projects and the strategies to deal with the negative impacts. In addition, from a life cycle perspective, the used articles in this study were grouped into different categories based on project stages. This promotes an integrated and comprehensive understanding of historical studies. Moreover, on the basis of a comprehensive review, this paper puts forward future research directions to promote the sustainable development of the construction sector. © 2022, Emerald Publishing Limited.

10.
Huanjing Kexue Xuebao/Acta Scientiae Circumstantiae ; 42(5):119-128, 2022.
Article in Chinese | Scopus | ID: covidwho-1876200

ABSTRACT

Pollutants emitted from motor vehicles have become an important source of air pollution. Based on the traffic flow data of the expressways in Fujian Province, a high-resolution pollutant emission inventory of the expressways from January to July in 2020 was established by the bottom-up calculation method. The results show that under the influence of the COVID-19, the monthly average traffic flow and pollutant emissions of the expressways in Fujian province decreased firstly and then increased. Pollutant emissions reached the lowest in April, and quickly recovered to the pre-COVID-19 emission level in May. The pollutant emissions of the CO, HC, NOx, PM2.5 and PM10 in the middle stage of the COVID-19 decreased by 90.68%, 89.06%, 92.58%, 89.58% and 89.63%, respectively, compared with those in the post stage of the COVID-19. In the entire study period, different cities have different sharing rates of the pollutant emissions from motor vehicles, with Quanzhou, Fuzhou and Zhangzhou having higher motor vehicle emission sharing rates on the expressways. In terms of the vehicle types, the small passenger buses and the light trucks are the main contributors for CO and HC, and the heavy trucks and the light trucks are the main contributors for NOx and PM. In terms of the fuel types, the gasoline vehicle is the main source of CO and HC, and the diesel vehicle is the main source of NOx and PM. In terms of the emission standards, vehicles with China 3 and China 4 have the largest contribution rate to various pollutants. However, the spatial distribution of various pollutants is consistent, with the higher level emissions in the eastern coastal expressways, while the lower level emissions in the western inland expressways. From the spatial distribution of NOx emission intensity of Expressways in Fujian Province, the emission intensity of each section in March and April was at a very low level. Taking the main emission of the motor vehicle: NOx as a case, the Shenyang-Haikou Expressway section has the highest NOx emission intensity. Moreover, the Xiamen and Quanzhou sections of Shenyang-Haikou Expressway have relatively high exposure levels of motor vehicle pollution, while other sections have relatively low exposure levels. © 2022, Science Press. All right reserved.

11.
Engineering Construction and Architectural Management ; : 22, 2022.
Article in English | Web of Science | ID: covidwho-1853332

ABSTRACT

Purpose This study applied eye-tracking techniques and questionnaires within the framework of the Stimulus-Organism-Response Model (SOR) and Technology Acceptance Model (TAM), to investigate the influencing factors of the public acceptance of 5G base stations. Design/methodology/approach This study used a combination of eye-tracking experiments and questionnaires. The data were analyzed using partial least squares structural equation modeling (PLS-SEM). Findings (1) The Technology Acceptance Model (TAM) could be used to explain the effects on public acceptance of 5G base stations in the context of the COVID-19 pandemic. The public's perceived usefulness and ease of use of 5G base stations positively affects public acceptance of 5G base stations. (2) The public's perceived risk of 5G base stations has a negative influence on the public acceptance of 5G base stations. (3) The public's visual attention to the different valence information about 5G base stations positively impacts the perceived ease of use while having negative impacts on perceived risk. (4) Visual attention to various valence information of 5G base stations can indirectly influence public acceptance through the perceived risk. Originality/value Applying the SOR and TAM to data obtained from eye-tracking experiments and questionnaires, this study analyzed the factors and mechanisms influencing public acceptance of 5G base stations in the context of the COVID-19 pandemic.

12.
Religious Education ; : 14, 2022.
Article in English | Web of Science | ID: covidwho-1852660

ABSTRACT

This article reports on research exploring how religious involvement and commitment are related to post-pandemic well-being among Chinese university students. The Religious Commitment Inventory-10, the Religious Involvement Scale, and the Post-Pandemic Well-Being Scale were administered to 1739 university students selected from 119 comprehensive universities. Results showed that religious involvement and religious commitment significantly and positively predicted post-pandemic well-being beyond demographic variables. The significance of religious education and the limitations and contributions of this research are also discussed.

14.
Frontiers in Communication ; 7, 2022.
Article in English | Scopus | ID: covidwho-1847158

ABSTRACT

Journalists are always on the “second battlefield” of fighting against COVID-19. In the face of major public health events, their scientific literacy is directly related to the effect of emergency science popularization. Based on related surveys and interview data in China, this article reviews the research on journalists' scientific literacy, clarifies the value of scientific literacy in journalism, and analyzes the cognition and practice of journalist scientific literacy. Through the analysis of cognition and practice, it explores feasible ways to effectively improve scientific literacy. The study found that journalist scientific literacy has a unique value in the crisis period, but the real measurement and self-cognition are not high. In the post-epidemic era, the social construction of science communication is stronger, and the media need to achieve a high degree of interaction with the scientific community to transform authoritative knowledge into popular science. Journalists should improve scientific literacy from their learning and professional training while using new media technology to scientifically demonstrate information. Copyright © 2022 Hu.

15.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333510

ABSTRACT

BACKGROUND: COVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, is broadly expressed in many organs including heart. However, the cellular distribution of ACE2 in the human heart, particularly the failing heart is unknown. METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data in both normal and failing hearts, and characterized the ACE2 gene expression profile in various cell subsets, especially in cardiomyocyte subsets, as well as its interaction with gene networks relating to various defense and immune responses at the single cell level. RESULTS: The results demonstrated that ACE2 is present in cardiomyocytes (CMs), endothelial cells, fibroblasts and smooth muscle cells in the heart, while the number of ACE2-postive (ACE2+) CMs and ACE2 gene expression in these CMs are significantly increased in the failing hearts. Interestingly, both brain natriuretic peptides (BNP) and atrial natriuretic peptide (ANP) are significantly up-regulated in the ACE2+ CMs. Further analysis shows that ANP, BNP and ACE2 may form a negative feedback loop with a group of genes associated with the development of heart failure. To our surprise, we found that genes related to virus entry, virus replication and suppression of interferon-gamma(IFN-gamma)signaling are all up-regulated in CMs in failing hearts, and the increases were significantly higher in ACE2+ CMs as compared with ACE2 negative (ACE2-) CMs, suggesting that these ACE2+ CMs may be more vulnerable to virus infection. Since ACE2 expression is correlated with BNP expression, we further performed retrospective analysis of the plasma BNP levels and clinic outcome of 91 COVID-19 patients from a single-center. Patients with higher plasma BNP were associated with significantly higher mortality rate and expression levels of inflammatory and infective markers such as procalcitonin and C-reactive protein. CONCLUSION: In the failing heart, the upregulation of ACE2 and virus infection associated genes, as well as the increased expression of ANP and BNP could facilitate SARS-CoV-2 virus entry and replication in these vulnerable cardiomyocyte subsets. These findings may advance our understanding of the underlying molecular mechanisms of myocarditis associated with COVID-19.

16.
Indian Journal of Pharmaceutical Sciences ; 84(1):173-181, 2022.
Article in English | Scopus | ID: covidwho-1789978

ABSTRACT

Molecular docking technology was employed to predict and exploit potential main protein inhibitors of novel coronavirus ribonucleic acid dependent ribonucleic acid polymerase by virtual screening of twenty hundred thousand natural molecules in ZINC database. By targeting main protease of novel coronavirus by Schrodinger Maestro software and molecular dynamic simulation, the affinity and stability of the complex formed between the compound and the main protease of novel coronavirus were carefully analyzed. Base on high-throughput virtual screening, twelve compounds with higher molecular docking score were selected from twenty hundred thousand compounds database, compound ZINC000096222420 has the highest docking score of -8.693. The results from molecular dynamic simulation and binding free energy calculation reveal that the structure of the complex is highly stable, which has high potential to accelerate the development of anti-severe acute respiratory syndrome coronavirus 2 drugs. © 2022 Indian Pharmaceutical Association. All rights reserved.

17.
IEEE Transactions on Intelligent Transportation Systems ; 2022.
Article in English | Scopus | ID: covidwho-1788789

ABSTRACT

The rapid spread of the COVID-19 has not only affected personal health and economy, but also revolutionized people's lifestyles. As more people turn to work and socialize online, the development of unmanned technologies based on the Internet of Vehicles (IoV), such as unmanned delivery, unmanned vehicles, unmanned transportation, etc., will become an inevitable trend. However, all kinds of intelligent terminals for unmanned equipment require a large amount of data interaction with devices such as cloud servers, mobile terminals, and roadside terminals, which poses cyber security risks. Furthermore, the outbreak of COVID-19 has prompted people to put forward higher demands for the security of network communications. Unfortunately, the current intrusion detection methods based on machine learning still have weaknesses such as low accuracy and low efficiency when faced with unbalanced data distribution. To solve the above problems, we propose a novel Tree-based BLS (TBLS) intrusion detection method according to the idea of ensemble learning and decision tree (CART and J48). The performance of TBLS was tested on the NSL-KDD dataset and the UNSW-NB15 dataset respectively, which contain a variety of malicious traffic types for attacks on the IoV. The results show that our proposed method can achieve higher accuracy rate and lower false alarm rate, compared with the existing 16 solutions. IEEE

18.
Journal of Environmental Sciences (China) ; 125:603-615, 2023.
Article in English | Scopus | ID: covidwho-1783484

ABSTRACT

Wuhan Tianhe International Airport (WUH) was suspended to contain the spread of COVID-19, while Shanghai Hongqiao International Airport (SHA) saw a tremendous flight reduction. Closure of a major international airport is extremely rare and thus represents a unique opportunity to straightforwardly observe the impact of airport emissions on local air quality. In this study, a series of statistical tools were applied to analyze the variations in air pollutant levels in the vicinity of WUH and SHA. The results of bivariate polar plots show that airport SHA and WUH are a major source of nitrogen oxides. NOx, NO2 and NO diminished by 55.8%, 44.1%, 76.9%, and 40.4%, 33.3% and 59.4% during the COVID-19 lockdown compared to those in the same period of 2018 and 2019, under a reduction in aircraft activities by 58.6% and 61.4%. The concentration of NO2, SO2 and PM2.5 decreased by 77.3%, 8.2%, 29.5%, right after the closure of airport WUH on 23 January 2020. The average concentrations of NO, NO2 and NOx scatter plots at downwind of SHA after the lockdown were 78.0%, 47.9%, 57.4% and 62.3%, 34.8%, 41.8% lower than those during the same period in 2018 and 2019. However, a significant increase in O3 levels by 50.0% and 25.9% at WUH and SHA was observed, respectively. These results evidently show decreased nitrogen oxides concentrations in the airport vicinity due to reduced aircraft activities, while amplified O3 pollution due to a lower titration by NO under strong reduction in NOx emissions. © 2022

19.
Journal of Virology ; 96(1):11, 2022.
Article in English | Web of Science | ID: covidwho-1756184

ABSTRACT

Over the past 20 years, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2 emerged, causing severe human respiratory diseases throughout the globe. Developing broad-spectrum drugs would be invaluable in responding to new, emerging coronaviruses and to address unmet urgent clinical needs. Main protease (Mpro;also known as 3CL(pro)) has a major role in the coronavirus life cycle and is one of the most important targets for anti-coronavirus agents. We show that a natural product, noncovalent inhibitor, shikonin, is a pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus (HCoV)-HKU1, HCoV-NL63, and HCoV-229E with micromolar half maximal inhibitory concentration (IC50) values. Structures of the main protease of different coronavirus genus, SARS-CoV from the betacoronavirus genus and HCoV-NL63 from the alphacoronavirus genus, were determined by X-ray crystallography and revealed that the inhibitor interacts with key active site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses as well as emerging coronaviruses of the future. Given the importance of the main protease for coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents. IMPORTANCE The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anticoronavirus agents. We solved the crystal structures of the main protease of SARSCoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.

20.
Non-conventional in English | National Technical Information Service, Grey literature | ID: grc-753531

ABSTRACT

The first step of SARS-CoV-2 infection is binding of the spike proteins receptor binding domain to the host cells ACE2 receptor on the plasma membrane. Here, we have generated a versatile imaging probe using recombinant Spike receptor binding domain conjugated to fluorescent quantum dots (QDs). This probe is capable of engaging in energy transfer quenching with ACE2-conjugated gold nanoparticles to enable monitoring of the binding event in solution. Neutralizing antibodies and recombinant human ACE2 blocked quenching, demonstrating a specific binding interaction. In cells transfected with ACE2-GFP, we observed immediate binding of the probe on the cell surface followed by endocytosis. Neutralizing antibodies and ACE2-Fc fully prevented binding and endocytosis with low nanomolar potency. Importantly, we will be able to use this QD nanoparticle probe to identify and validate inhibitors of the SARS-CoV-2 Spike and ACE2 receptor binding in human cells. This work enables facile, rapid, and high-throughput cell-based screening of inhibitors for coronavirus Spike-mediated cell recognition and entry.

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