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1.
Front Pediatr ; 9: 801436, 2021.
Article in English | MEDLINE | ID: covidwho-1775736

ABSTRACT

Objective: The study is designed to understand the situation of full-term infants breastfeeding within 6 months of birth in Xi'an before the Covid-19 pandemic and analyze the influencing factors of exclusive breastfeeding. Methods: Five hospitals in Xi'an province have been selected as research centers. Full-term infants who met the inclusion and exclusion criteria were recruited from these centers between January 1 and February 28, 2019. The feeding situation at 10 days, 42 days, 3 months, and 6 months after birth were investigated. A self-designed breastfeeding questionnaire was used for investigation and follow-up. SPSS 22.0 was applied for statistical analysis of the data. Results: The exclusive breastfeeding rate of full-term infants on days 10 and 42 and at months three and six after birth was 61.38%, 54.78%, 48.83%, and 38.78%, respectively, with a decreasing trend over time. During breastfeeding within 48 h after delivery, 1,653 cases (91.83%) of puerpera had different grades of pain, including 1,325 cases (80.16%) of mild discomfort, 321 cases (19.42%) of moderate pain, and seven cases (0.42%) of severe pain. Within 24-48 h postpartum, 1,607 (89.27%) mothers faced problems related to postpartum breastfeeding. Among them, 694 (43,19%) neonates could not be fed effectively; 665 (41.38%) mothers had wound pain and had inconvenience to turn over; 598 (37.21%) neonates were difficult to wake up; 439 (27.32%) mothers had incorrect feeding posture; 181 (11.26%) mothers experienced other problems. The Cox risk regression model showed that weight gain during pregnancy was higher than the recommended standard. Living in suburban counties was a risk factor of exclusive breastfeeding for full-term infants. Participation in breastfeeding courses during pregnancy, feeding more than eight times daily after delivery, were the protective factors of exclusive breastfeeding for full-term infants. Conclusion: The body weight gain of parturients should be controlled within a reasonable range during pregnancy. Parturients were encouraged by medical staff to participate in breastfeeding courses or watch the breastfeeding process during pregnancy to increase their self-confidence and improve the rate of exclusive breastfeeding for full-term infants. In addition, it is necessary to strengthen the publicity of breastfeeding in suburban areas to promote breastfeeding.

2.
Medicina (Kaunas) ; 58(3)2022 Mar 20.
Article in English | MEDLINE | ID: covidwho-1760771

ABSTRACT

A 48-year-old female patient underwent a heart transplantation for acute fulminant myocarditis, following heterologous vaccination with the ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19. She had no history of severe acute respiratory syndrome coronavirus-2 infection. She did not exhibit clinical signs or have laboratory findings of concomitant infection before or after vaccination. Heart transplantation was performed because her heart failed to recover with venoarterial extracorporeal oxygenation support. Organ autopsy revealed giant cell myocarditis, possibly related to the vaccines. Clinicians may have to consider the possibility of the development of giant cell myocarditis, especially in patients with rapidly deteriorating cardiac function and myocarditis symptoms after COVID-19 vaccination.


Subject(s)
COVID-19 , Myocarditis , COVID-19 Vaccines/adverse effects , Female , Giant Cells , Humans , Middle Aged , Myocarditis/etiology , Vaccination/adverse effects
3.
Behav Sci (Basel) ; 12(3)2022 Feb 25.
Article in English | MEDLINE | ID: covidwho-1760383

ABSTRACT

BACKGROUND: The main purpose of this study was to investigate the effects of exercise intensity and exercise frequency on anxiety, depression and sleep quality in college students. METHODS: All participants came from a university in northeastern China. All participants were tested for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and were diagnosed with anxiety disorders. The research subjects were divided into six groups, namely the low-intensity and low-frequency group (group 1), low-intensity and moderate-frequency group (group 2), low-intensity and high-frequency group (group 3), high-intensity and low-frequency group (group 4), and high-intensity and moderate-frequency group (group 5) and high-intensity and high-frequency group (group 6). The duration of each physical exercise for each group was 1 h. Participants' exercise intensity was monitored using Polar H10 HR sensors and the Borg RPE scale. The experiment was carried out for a total of 6 weeks. The researchers conducted pre- and post-test scores on the subjects' anxiety, depression and sleep quality through questionnaires. RESULTS: Exercise intensity improved anxiety and decreased symptoms of depression better than exercise frequency; sleep quality was more closely related to exercise intensity. CONCLUSION: Exercise intensity and exercise frequency have different effects on anxiety, depression and sleep quality improvement, indicating that exercise intensity and exercise frequency have different effects on anxiety, depression and sleep quality of college students.

4.
Brain Behav Immun ; 87: 11-17, 2020 07.
Article in English | MEDLINE | ID: covidwho-1719332

ABSTRACT

The severe 2019 outbreak of novel coronavirus disease (COVID-19), which was first reported in Wuhan, would be expected to impact the mental health of local medical and nursing staff and thus lead them to seek help. However, those outcomes have yet to be established using epidemiological data. To explore the mental health status of medical and nursing staff and the efficacy, or lack thereof, of critically connecting psychological needs to receiving psychological care, we conducted a quantitative study. This is the first paper on the mental health of medical and nursing staff in Wuhan. Notably, among 994 medical and nursing staff working in Wuhan, 36.9% had subthreshold mental health disturbances (mean PHQ-9: 2.4), 34.4% had mild disturbances (mean PHQ-9: 5.4), 22.4% had moderate disturbances (mean PHQ-9: 9.0), and 6.2% had severe disturbance (mean PHQ-9: 15.1) in the immediate wake of the viral epidemic. The noted burden fell particularly heavily on young women. Of all participants, 36.3% had accessed psychological materials (such as books on mental health), 50.4% had accessed psychological resources available through media (such as online push messages on mental health self-help coping methods), and 17.5% had participated in counseling or psychotherapy. Trends in levels of psychological distress and factors such as exposure to infected people and psychological assistance were identified. Although staff accessed limited mental healthcare services, distressed staff nonetheless saw these services as important resources to alleviate acute mental health disturbances and improve their physical health perceptions. These findings emphasize the importance of being prepared to support frontline workers through mental health interventions at times of widespread crisis.


Subject(s)
Anxiety Disorders/psychology , Coronavirus Infections/therapy , Depressive Disorder/psychology , Nurses/psychology , Physicians/psychology , Pneumonia, Viral/therapy , Sleep Initiation and Maintenance Disorders/psychology , Adaptation, Psychological , Adolescent , Adult , Anxiety/epidemiology , Anxiety/psychology , Anxiety Disorders/epidemiology , Betacoronavirus , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Depression/psychology , Depressive Disorder/epidemiology , Disease Outbreaks , Female , Health Services Accessibility , Humans , Male , Mental Health , Mental Health Services , Middle Aged , Nurses/statistics & numerical data , Pandemics , Patient Health Questionnaire , Physicians/statistics & numerical data , Pneumonia, Viral/epidemiology , Psychological Distress , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/epidemiology , Surveys and Questionnaires , Young Adult
5.
Polymers (Basel) ; 14(5)2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1715621

ABSTRACT

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disease prevention has become incredibly important. Consequently, mask and air-purifier use has increased. The filter is the core component of these items. However, most filter materials lack antimicrobial properties. Copper is a sustainable antimicrobial material. When copper is deposited onto the filter's surface, the microorganisms that come into contact with it can be effectively inactivated. In this study, we used an oxygen ion beam with a controlled process temperature to treat filter surfaces with copper. This enabled a strong adhesion of at least 4 N/cm between the copper and the filter fibers without damaging them. Upon exposing the filter to bacteria (Staphylococcus aureus ATCC 6538, Klebsiella pneumoniae ATCC 4352, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853) for one hour, a >99.99% removal rate was attained; when the filter was exposed to SARS-CoV-2 virus for one hour, it inactivated more than 99%. These beneficial properties minimize the risk of secondary infections, which are significantly more likely to occur when a conventional filter is replaced or removed.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325301

ABSTRACT

Traditional Chinese medicine (TCM) has played an important role in the prevention and control of the novel coronavirus pneumonia (COVID-19), and community prevention has become the most essential part in reducing the spread risk and protecting populations. However, most communities use a uniform TCM prevention program for all residents, which violates the "treatment based on syndrome differentiation" principle of TCM and limits the effectiveness of prevention. In this paper, we propose an intelligent optimization method to develop diversified TCM prevention programs for community residents. First, we use a fuzzy clustering method to divide the population based on both modern medicine and TCM health characteristics;we then use an interactive optimization method, in which TCM experts develop different TCM prevention programs for different clusters, and a heuristic algorithm is used to optimize the programs under the resource constraints. We demonstrate the computational efficiency of the proposed method and report its successful application to TCM-based prevention of COVID-19 in 12 communities in Zhejiang province, China, during the peak of the pandemic.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324155

ABSTRACT

The outbreak of the 2019 novel coronavirus disease (COVID-19) infection in China had quickly spread worldwide. Recent reports showed that conjunctivitis symptoms were found in a small number of adult patients diagnosed with COVID-19. But rare children diagnosed with COVID-19 were reported to have eye symptoms. Our case showed a 2 years and 10 months old child confirmed COVID-19 had no symptoms other than conjunctivitis and eyelid dermatitis, suggesting that doctors shouldn’t forget to conduct COVID-19 screening when children come to hospital for ocular surface symptoms during this epidemic period.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308927

ABSTRACT

Change point detection in time series has attracted substantial interest, but most of the existing results have been focused on detecting change points in the time domain. This paper considers the situation where nonlinear time series have potential change points in the state domain. We apply a density-weighted anti-symmetric kernel function to the state domain and therefore propose a nonparametric procedure to test the existence of change points. When the existence of change points is affirmative, we further introduce an algorithm to estimate their number together with locations and show the convergence result on the estimation procedure. A real dataset of German daily confirmed cases of COVID-19 is used to illustrate our results.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315261

ABSTRACT

Background: Given that 2019 novel coronavirus (COVID-19) spreads rapidly, it is critical to make rapid and accurate detection of COVID-19 patients towards containment of SARS-CoV-2 virus. At present, COVID-19 patients are mainly identified through viral nuclear acid testing (NAT). However, factors such as time for patients being tested, experience of test operators, and specimen’s preparation, might affect the accuracy of testing results. The purpose of this study was to use different classification and feature selection methods to improve the diagnostic accuracy of COVID-19 patients. Methods: We utilized seven machine learning algorithms for assisting diagnosis of COVID-19 by developing a non-NAT algorithm. In order to reduce the number of input features while maintaining the models’ performance so as to decrease the cost and time consumption, we adopted three algorithms, such as Chi-square test, variance analysis, and feature importance tests to identify the optimal feature sets. Findings: The XGBoost and RF models displayed the best performance for COVID-19 detection, with the highest accuracy rate more than 0·96. The accuracy of RF model was 0·968 when using only ten hematological features and body temperature. Interpretation: Ten blood features and body temperature can fairly accurately determine whether a suspected patient is infected with COVID-19. Our model can improve the diagnostic accuracy of COVID-19 and reduce the spread. Funding: This work is supported by grants from the National Key Research and Development Program of China under Grant 2017YFE0123600, the Natural Science Foundation of China (81873931, 81974382 and 81773104), the Frontier Exploration Program of Huazhong University of Science and Technology (2015TS153), and the Major Scientific and Technological Innovation Projects in Hubei Province (2018ACA136).Declaration of Interests: All the authors stated that the paper had never been published elsewhere, and that there were no competing economic interests.Ethics Approval Statement: The collection, use, and retrospective analysis of chest CT images, CFs and SARS-CoV-2 nucleic acid PCR results of patients were approved by the institutional ethical committees of HUST-UH (IRB ID: [2020] IEC(A001)).

11.
PLoS One ; 16(12): e0261778, 2021.
Article in English | MEDLINE | ID: covidwho-1613357

ABSTRACT

Many CRISPR/Cas platforms have been established for the detection of SARS-CoV-2. But the detection platform of the variants of SARS-CoV-2 is scarce because its specificity is very challenging to achieve for those with only one or a few nucleotide(s) differences. Here, we report for the first time that chimeric crRNA could be critical in enhancing the specificity of CRISPR-Cas12a detecting of N501Y, which is shared by Alpha, Beta, Gamma, and Mu variants of SARS-CoV-2 without compromising its sensitivity. This strategy could also be applied to detect other SARS-CoV-2 variants that differ only one or a few nucleotide(s) differences.


Subject(s)
COVID-19/diagnosis , Nucleic Acid Amplification Techniques/methods , SARS-CoV-2/genetics , COVID-19/genetics , CRISPR-Cas Systems/genetics , DNA Primers/genetics , Diagnostic Tests, Routine/methods , Humans , Mutation/genetics , RNA, Guide/genetics , RNA, Guide/metabolism , Sensitivity and Specificity
12.
Toxics ; 9(12)2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1592920

ABSTRACT

Polyethylene glycol (PEG) is a polymer used for surface modification of important substances in the modern pharmaceutical industry and biopharmaceutical fields. Despite the many benefits of PEGylation, there is also the possibility that the application and exposure of the substance may cause adverse effects in the body, such as an immune response. Therefore, we aimed to evaluate the sensitization responses that could be induced through the intercomparison of nanomaterials of the PEG-coated group with the original group. We selected gold/silver nanomaterials (NMs) for original group and PEGylated silver/gold NMs in this study. First, we measured the physicochemical properties of the four NMs, such as size and zeta potential under various conditions. Additionally, we performed the test of the NM's sensitization potential using the KeratinoSens™ assay for in vitro test method and the LLNA: 5-bromo-2-deoxyuridine (BrdU)-FCM for in vivo test method. The results showed that PEGylated-NMs did not lead to skin sensitization according to OECD TG 442 (alternative test for skin sensitization). In addition, gold nanomaterial showed that cytotoxicity of PEGylated-AuNMs was lower than AuNMs. These results suggest the possibility that PEG coating does not induce an immune response in the skin tissue and can lower the cytotoxicity of nanomaterials.

13.
JCI Insight ; 6(24)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1518198

ABSTRACT

A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1ß, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cell-mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.


Subject(s)
COVID-19/complications , Cytokines/immunology , Immune Checkpoint Inhibitors/pharmacology , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , B7-H1 Antigen/immunology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Case-Control Studies , Cytokines/drug effects , DNA Methylation , Female , Humans , Immunophenotyping , In Vitro Techniques , Interleukin 1 Receptor Antagonist Protein/drug effects , Interleukin 1 Receptor Antagonist Protein/immunology , Interleukin-1beta/drug effects , Interleukin-1beta/immunology , Interleukin-8/drug effects , Interleukin-8/immunology , Male , MicroRNAs/metabolism , Middle Aged , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Promoter Regions, Genetic
14.
Sustainability ; 13(22):12370, 2021.
Article in English | MDPI | ID: covidwho-1512644

ABSTRACT

This paper adopts the GDYN model to estimate the dynamic impact of the COVID-19 pandemic on global manufacturing industry and the value chain. Our simulation finds that (1) In the short run, the low-tech manufacturing industries will suffer greater shocks, with a decline of output growth in 2021 by 6.0%. The growth rate of the high-tech manufacturing industry showed an increasing trend of 3.7% in 2021. (2) In the post-epidemic period, the total manufacturing output will return to the baseline level, from which the growth rate of low-tech manufacturing will rebound, demonstrating a V-shaped development trajectory. (3) From the perspective of Global Value Chain (GVC), the participation in GVCs of manufacturers in countries along the Belt and Road, the European Union and the United States will weaken, while China’s manufacturing industry has witnessed an obvious improvement in export competitiveness. The import added value of China has decreased, which shows that its ability to meet domestic demand has been improving. This indicates that the COVID-19 pandemic is providing a crucial opportunity for China to upgrade its manufacturing value chain, which contributes to the accelerated construction of a new dual-cycle development pattern.

15.
Sci China Life Sci ; 2021 Oct 21.
Article in English | MEDLINE | ID: covidwho-1491326

ABSTRACT

As coronavirus disease 2019 (COVID-19) threatens human health globally, infectious disorders have become one of the most challenging problem for the medical community. Natural products (NP) have been a prolific source of antimicrobial agents with widely divergent structures and a range vast biological activities. A dataset comprising 618 articles, including 646 NP-based compounds from 672 species of natural sources with biological activities against 21 infectious pathogens from five categories, was assembled through manual selection of published articles. These data were used to identify 268 NP-based compounds classified into ten groups, which were used for network pharmacology analysis to capture the most promising lead-compounds such as agelasine D, dicumarol, dihydroartemisinin and pyridomycin. The distribution of maximum Tanimoto scores indicated that compounds which inhibited parasites exhibited low diversity, whereas the chemistries inhibiting bacteria, fungi, and viruses showed more structural diversity. A total of 331 species of medicinal plants with compounds exhibiting antimicrobial activities were selected to classify the family sources. The family Asteraceae possesses various compounds against C. neoformans, the family Anacardiaceae has compounds against Salmonella typhi, the family Cucurbitacea against the human immunodeficiency virus (HIV), and the family Ancistrocladaceae against Plasmodium. This review summarizes currently available data on NP-based antimicrobials against refractory infections to provide information for further discovery of drugs and synthetic strategies for anti-infectious agents.

16.
Management Decision ; 59(11):2660-2673, 2021.
Article in English | ProQuest Central | ID: covidwho-1494240

ABSTRACT

(Ma et al., 2019) It is necessary for theoretical studies to further examine solution modes of a sharing economy that focus on social issues and how to promote social innovation and entrepreneurship by means of sharing values and concepts to verify the relationship between social innovation and social value creation and understand various problems, such as how social innovation and entrepreneurship and sharing values and concepts can realize interactive promotion. [...]it is necessary to explore how we can break through the conceptual limitations of the “means-ends” relationship in the economy and society, so as to not only improve the survival ability of social organizations but also prompt enterprises and organizations to return to their essential attributes: social subjects. [...]nonprofit organizations engage in voluntary public welfare or mutual assistance activities, which can make up for the shortcomings of the government and other public departments and help them provide more effective social services to meet social needs while creating social value. Theoretical studies based on the concept of sustainable development have addressed the issue through paradigms of active social changes, such as CSR, the bottom of the pyramid (BoP) and SE (Mair et al., 2016;Zahra and Wright, 2016). [...]increasingly more organizations are beginning to pay attention to economic value and social value simultaneously. [...]according to the organizational paradox theory, in theoretical studies, we must first recognize that these two value goals have long existed in enterprises and are interrelated and contradictory. [...]the paradox theory advocates treating the tension of contradiction as an organizational opportunity and finding innovative ways to solve complex problems, such as sustainable development, through the exploration of the relationship between the relevant elements of the contradiction (Hahn et al., 2018;Smith and Lewis, 2011), which is becoming the focus of theoretical studies.

18.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Article in English | MEDLINE | ID: covidwho-1450313

ABSTRACT

Cancer therapy reduces tumor burden via tumor cell death ("debris"), which can accelerate tumor progression via the failure of inflammation resolution. Thus, there is an urgent need to develop treatment modalities that stimulate the clearance or resolution of inflammation-associated debris. Here, we demonstrate that chemotherapy-generated debris stimulates metastasis by up-regulating soluble epoxide hydrolase (sEH) and the prostaglandin E2 receptor 4 (EP4). Therapy-induced tumor cell debris triggers a storm of proinflammatory and proangiogenic eicosanoid-driven cytokines. Thus, targeting a single eicosanoid or cytokine is unlikely to prevent chemotherapy-induced metastasis. Pharmacological abrogation of both sEH and EP4 eicosanoid pathways prevents hepato-pancreatic tumor growth and liver metastasis by promoting macrophage phagocytosis of debris and counterregulating a protumorigenic eicosanoid and cytokine storm. Therefore, stimulating the clearance of tumor cell debris via combined sEH and EP4 inhibition is an approach to prevent debris-stimulated metastasis and tumor growth.


Subject(s)
Eicosanoids/metabolism , Epoxide Hydrolases/biosynthesis , Macrophages/immunology , Neoplasm Metastasis/pathology , Receptors, Prostaglandin E, EP4 Subtype/biosynthesis , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/pathology , Cell Death/drug effects , Cell Line, Tumor , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/prevention & control , Cytokines/metabolism , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Male , Mice , Mice, Inbred C57BL , Neoplasm Metastasis/prevention & control , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Phagocytosis/immunology , RAW 264.7 Cells
19.
International Journal of Environmental Research and Public Health ; 17(11), 2020.
Article in English | CAB Abstracts | ID: covidwho-1409524

ABSTRACT

COVID-19 has globally spread to over 4 million people and the epidemic situation in Japan is very serious. The purpose of this research was to assess the risk of COVID-19 epidemic dissemination in Japan by estimating the current state of epidemic dissemination and providing some epidemic prevention and control recommendations. Firstly, the period from 6 January to 31 March 2020 was divided into four stages and the relevant parameters were estimated according to the imported cases in Japan. The basic reproduction number of the current stage is 1.954 (95% confidence interval (CI) 1.851-2.025), which means COVID-19 will spread quickly, and the self-healing rate of Japanese is about 0.495 (95% CI 0.437-0.506), with small variations in the four stages. Secondly, the results were applied to the actual reported cases from 1 to 5 April 2020, verifying the reliability of the estimated data using the accumulated reported cases located within the 95% confidence interval and the relative error of forecast data of five days being less than 2.5% 2.5%. Thirdly, considering the medical resources in Japan, the times the epidemic beds and ventilators become fully occupied are predicted as 5 and 15 May 2020, respectively. Keeping with the current situation, the final death toll in Japan may reach into the millions. Finally, based on experience with COVID-19 prevention and control in China, robust measures such as nationwide shutdown, store closures, citizens isolating themselves at home, and increasing PCR testing would quickly and effectively prevent COVID-19 spread.

20.
Eur J Med Chem ; 215: 113286, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-1385487

ABSTRACT

Covalent drugs have been intensively studied in some very important fields such as anti-tumor and anti-virus, including the currently global-spread SARS-CoV-2. However, these drugs may interact with a variety of biological macromolecules and cause serious toxicology, so how to reactivate the inhibited targets seems to be imperative in the near future. Organophosphate was an extreme example, which could form a covalent bound easily with acetylcholinesterase and irreversibly inhibited the enzyme, causing high toxicology. Some nucleophilic oxime reactivators for organophosphate poisoned acetylcholinesterase had been developed, but the reactivation process was still less understanding. Herein, we proposed there should be a pre-reactivated pose during the reactivating process and compounds whose binding pose was easy to transfer to the pre-reactivated pose might be efficient reactivators. Then we refined the previous reactivators based on the molecular dynamic simulation results, the resulting compounds L7R3 and L7R5 were proven as much more efficient reactivators for organophosphate inhibited acetylcholinesterase than currently used oximes. This work might provide some insights for constructing reactivators of covalently inhibited targets by using computational methods.


Subject(s)
Acetylcholinesterase/chemistry , Cholinesterase Reactivators/chemistry , Acetylcholinesterase/metabolism , Cholinesterase Inhibitors/chemistry , Cholinesterase Reactivators/metabolism , Humans , Kinetics , Molecular Dynamics Simulation , Organophosphorus Compounds/chemistry , Proof of Concept Study , Protein Binding
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