Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 32
Filter
1.
Journal of Medicinal Chemistry ; 15:15, 2022.
Article in English | MEDLINE | ID: covidwho-2028635

ABSTRACT

The continuous spread of SARS-CoV-2 calls for more direct-acting antiviral agents to combat the highly infectious variants. The main protease (Mpro) is an promising target for anti-SARS-CoV-2 drug design. Here, we report the discovery of potent non-covalent non-peptide Mpro inhibitors featuring a 1,2,4-trisubstituted piperazine scaffold. We systematically modified the non-covalent hit MCULE-5948770040 by structure-based rational design combined with multi-site binding and privileged structure assembly strategies. The optimized compound GC-14 inhibits Mpro with high potency (IC50 = 0.40 muM) and displays excellent antiviral activity (EC50 = 1.1 muM), being more potent than Remdesivir. Notably, GC-14 exhibits low cytotoxicity (CC50 > 100 muM) and excellent target selectivity for SARS-CoV-2 Mpro (IC50 > 50 muM for cathepsins B, F, K, L, and caspase 3). X-ray co-crystal structures prove that the inhibitors occupy multiple subpockets by critical non-covalent interactions. These studies may provide a basis for developing a more efficient and safer therapy for COVID-19.

2.
Journal of Contemporary Chinese Art ; 9(1-2):239-247, 2022.
Article in English | Web of Science | ID: covidwho-1997352

ABSTRACT

The London-based multimedia artist Lisa Chang Lee, born in Beijing, China, is a representative example of exploring alternative identification in the context of the global health and environmental crisis. The conversation focuses on her artistic experiments with algorithms and digital technologies to transcend established norms of 'Chineseness' culturally and artistically. Gao Shiyu will investigate Lee's projects to question the binary distinctions between humans and non-humans, nature and culture, the East and the West. The discussion intends to show a shift in the new generation of diasporic Chinese artists' creative practices and challenge the tendency in contemporary Chinese art criticism that locates these works in large-scale, systemic and political ways.

3.
J Med Virol ; 2022.
Article in English | PubMed | ID: covidwho-1990500

ABSTRACT

Rapid detection of antibodies during infection and after vaccination is critical for the control of infectious outbreaks, understanding immune response, and evaluating vaccine efficacy. In this manuscript, we evaluate a simple ultra-rapid test for SARS-CoV-2 antibodies in COVID-19 patients, which gives quantitative results (i.e., antibody concentration) in 10-15 seconds using a previously reported nanomaterial-based 3D-printed biosensing platform. This platform consists of a micropillar array electrode fabricated via 3D printing of aerosolized gold nanoparticles and coated with nanoflakes of graphene and specific SARS-CoV-2 antigens, including spike S1, S1 receptor-binding domain (RBD) and nucleocapsid (N). The sensor works on the principle of electrochemical transduction where the change of sensor impedance is realized by the interactions between the viral proteins attached to the sensor electrode surface and the antibodies. The three sensors were used to test samples from 17 COVID-19 patients and 3 patients without COVID-19. Unlike other serological tests, the 3D sensors quantitatively detected antibodies at concentration as low as picomole within 10-12 seconds in human plasma samples. We found that the studied COVID-19 patients had higher concentrations of antibodies to spike proteins (RBD and S1) than to the N protein. These results demonstrate the enormous potential of the rapid antibody test platform for understanding patients' immunity, disease epidemiology and vaccine efficacy, and facilitating control and prevention of infectious epidemics. This article is protected by copyright. All rights reserved.

4.
Neurology Perspectives ; 2(1):9-20, 2022.
Article in English, Spanish | Scopus | ID: covidwho-1959889

ABSTRACT

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the disease COVID-19, has caused a pandemic that has rapidly affected the whole world and caused a significant threat to public health. The aim of this study was to investigate and analyze the social and occupational effects of the COVID-19 pandemic on patients with multiple sclerosis (MS) in three different countries: China, Spain, and Cuba. Methods: A cross-sectional survey was designed to assess the social and occupational effects of the COVID-19 pandemic in MS patients in these three countries, using a 25-item anonymous online questionnaire, structured into three sections. Quantitative data are expressed as mean (standard deviation), and quantitative data as absolute frequency and percentage. Results: A total of 361 participants responded to the questionnaire: 194 from China, 104 from Spain, and 63 from Cuba. We found no cases of COVID-19 among Chinese patients with MS, and few cases in Spain and Cuba. Respondents reported different levels of impact on relationships with friends, family, and colleagues, and patients in all three countries described increased use of digital or social media platforms. Spanish patients reported a significantly less negative impact than those in Cuba and China. Mental and cognitive effects were similar in all three countries, although China seemed to have a better situation. We also found that the time spent exercising decreased at specific points during the pandemic, but with few changes in dietary habits. Patients reported little or no change in their means of transport in all three countries. Most patients in all three countries reported little or no physical deterioration, especially in Chinese patients (82.47%), compared to the Spanish (70.20%) and Cuban respondents (73.02%). In general, patients from all three countries demonstrated confidence in overcoming the COVID-19 pandemic, although to a lesser extent among Spanish respondents. Conclusions: During the pandemic, family support was more effective in China than in Cuba and Spain. Neither COVID-19 infections nor the number of MS relapses increased significantly during lockdown in any of the three countries. Regarding their economic situation, Spanish MS patients reported a significantly less severe negative impact than those in Cuba and China. Patients from all three countries used digital or social media platforms more frequently, probably to maintain personal relationships. Chinese and Cuban respondents were more confident of the control of the pandemic than the Spanish, who were more pessimistic. © 2021

5.
2022 International Conference on Optics and Machine Vision, ICOMV 2022 ; 12173, 2022.
Article in English | Scopus | ID: covidwho-1932600

ABSTRACT

Covid-19 pandemic continues to threat health of the global population, an efficient way to restrain the Covid-19 outbreak is timely screening suspected cases for quarantine and treatment. Despite of pathogenic laboratory testing is the gold standard to screen suspected cases, but it may obtain false negative results and consuming a lot of time. Computed tomography of chest can be an alternative diagnostic method to screen suspected cases that is based on radio graphical changes in lung area of Covid-19 confirmed case. Precisely delineate the lung area that is first and critical step for screening computed tomography image of chest by using deep learning method. In this paper, several related previous works will be introduced at first. Then, an improved encoder-decoder based segmentation framework is proposed, which is integrated with multi-scale densely connection-based convolution block and skip connection path. Moreover, in model training process, a semi-supervised manner is applied to train model which can reduce the demand of labeled training data. Finally, the proposed method is tested with a dataset of public X-ray image of chest. The experiment test proposed model in this paper with varieties of segmentation methods and result demonstrates promising performance of proposed model that against several other deep learning models. © 2022 SPIE

6.
2nd International Conference on Bioinformatics and Intelligent Computing, BIC 2022 ; : 1-5, 2022.
Article in English | Scopus | ID: covidwho-1902107

ABSTRACT

Since the outbreak and spread of COVID-19 in large areas of the world, the importance of rapid diagnosis of COVID-19 has increased. In the first week after the onset of COVID-19, the density of lesions is uneven, and chest CT is often difficult to show local subpleural ground-glass shadows, resulting in missed diagnosis. The COVID-19 intelligent diagnosis system based on the convolutional neural network algorithm can not only accurately identify the feature points, reduce the workload of doctors and improve the diagnosis efficiency, but also reduce the rate of missed diagnosis and misdiagnosis, which is conducive to epidemic control. © 2022 ACM.

7.
Informs Journal on Applied Analytics ; : 16, 2022.
Article in English | Web of Science | ID: covidwho-1886976

ABSTRACT

This study examines the impact of coronavirus disease 2019 (COVTD-19) test accuracy (i.e., sensitivity and specificity) on the progression of the pandemic under two scenarios of limited and unlimited test capacity. We extend the classic susceptible-exposed-infectious-recovered model to incorporate test accuracy and compare the progression of the pandemic under various sensitivities and specificities. We find that high-sensitivity tests effectively reduce the total number of infections only with sufficient testing capacity. Nevertheless, with limited test capacity and a relatively high cross-infection rate, the total number of infected cases may increase when sensitivity is above a certain threshold. Despite the potential for higher sensitivity tests to identify more infected individuals, more false positive cases occur, which wastes limited testing capacity, slowing down the detection of infected cases. Our findings reveal that improving test sensitivity alone does not always lead to effective pandemic control, indicating that policymakers should balance the trade-off between high sensitivity and high false positive rates when designing containment measures for infectious diseases, such as COVID-19, particularly when navigating limited test capacity.

8.
Language and Intercultural Communication in Tourism: Critical Perspectives ; : 1-14, 2021.
Article in English | Scopus | ID: covidwho-1863129

ABSTRACT

One pertinent challenge in studying intercultural communication is posed by the fast-changing reality of our societies on a global scale, which has been made even more tricky and complex due to Covid-19. Intercultural communication is a discipline characterized by diverse research paradigms and methodologies, so it is important to establish how the people understand and approach intercultural communication in this volume. It may seem self-evident that tourism is about engagement with the other and therefore constitutes a key site of intercultural communication. This introduction presents an overview of the key concepts discussed in the subsequent chapters of this book. The book looks at interculturality in the promotion of tourist destinations. It focuses on tourism encounters wherein intercultural identity is performed and constructed. The pandemic has created a new discursive space for tourism scholars. The existing forms of inequalities created by neoliberal capitalism have been perpetuated by the Covid-19 pandemic. © 2022 selection and editorial matter, Bal Krishna Sharma and Shuang Gao.

9.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-337380

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although unprecedented efforts are underway to develop therapeutic strategies against this disease, scientists have acquired only a little knowledge regarding the structures and functions of the CoV replication and transcription complex (RTC) and 16 non-structural proteins, named NSP1-16. Results: In the present study, we proposed a two-route model to answer how the RTC functions in the jumping transcription of CoVs. The key step leading to this model was that the motif AAACH for METTL3 recognition flanking the transcription regulatory sequence (TRS) motif was discovered to determine the m6A methylation of SARS-CoV-2 RNAs, by reanalyzing public Nanopore RNA-seq data. As the most important finding, TRS hairpins were reported for the first time to interpret NSP15 cleavage, RNA methylation of CoVs and their association at the molecular level. In addition, we reported canonical TRS motifs of all CoVs to prove the importance of our findings. Conclusions: The main conclusions are: (1) TRS hairpins can be used to identify recombination regions in CoV genomes;(2) RNA methylation of CoVs participates in the determination of the RNA secondary structures by affecting the formation of base pairing;and (3) The eventual determination of the CoV RTC global structure needs to consider METTL3 in the experimental design. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, providing a crucial basis for future studies.

10.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333514

ABSTRACT

BACKGROUND: The novel human coronavirus disease 2019 (COVID-19) pandemic has claimed more than 240,000 lives worldwide, causing tremendous public health, social, and economic damages. While the risk factors of COVID-19 are still under investigation, environmental factors, such as urban air pollution, may play an important role in increasing population susceptibility to COVID-19 pathogenesis. METHODS: We conducted a cross-sectional nationwide study using zero-inflated negative binomial models to estimate the association between long-term (2010-2016) county-level exposures to NO2, PM2.5 and O3 and county-level COVID-19 case-fatality and mortality rates in the US. We used both single and multipollutant models and controlled for spatial trends and a comprehensive set of potential confounders, including state-level test positive rate, county-level healthcare capacity, phase-of-epidemic, population mobility, sociodemographic, socioeconomic status, behavior risk factors, and meteorological factors. RESULTS: 1,027,799 COVID-19 cases and 58,489 deaths were reported in 3,122 US counties from January 22, 2020 to April 29, 2020, with an overall observed case-fatality rate of 5.8%. Spatial variations were observed for both COVID-19 death outcomes and long-term ambient air pollutant levels. County-level average NO2 concentrations were positively associated with both COVID-19 case-fatality rate and mortality rate in single-, bi-, and tri-pollutant models (p-values<0.05). Per inter-quartile range (IQR) increase in NO2 (4.6 ppb), COVID-19 case-fatality rate and mortality rate were associated with an increase of 7.1% (95% CI 1.2% to 13.4%) and 11.2% (95% CI 3.4% to 19.5%), respectively. We did not observe significant associations between long-term exposures to PM2.5 or O3 and COVID-19 death outcomes (p-values>0.05), although per IQR increase in PM2.5 (3.4 ug/m3) was marginally associated with 10.8% (95% CI: -1.1% to 24.1%) increase in COVID-19 mortality rate. DISCUSSIONS AND CONCLUSIONS: Long-term exposure to NO2, which largely arises from urban combustion sources such as traffic, may enhance susceptibility to severe COVID-19 outcomes, independent of long-term PM2.5 and O3 exposure. The results support targeted public health actions to protect residents from COVID-19 in heavily polluted regions with historically high NO2 levels. Moreover, continuation of current efforts to lower traffic emissions and ambient air pollution levels may be an important component of reducing population-level risk of COVID-19 deaths.

11.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(3): 399-404, 2022 Mar 20.
Article in Chinese | MEDLINE | ID: covidwho-1791799

ABSTRACT

OBJECTIVE: To analyze the mutations in transcription regulatory sequences (TRSs) of coronaviruss (CoV) to provide the basis for exploring the patterns of SARS-CoV-2 transmission and outbreak. METHODS: A combined evolutionary and molecular functional analysis of all sets of publicly available genomic data of viruses was performed. RESULTS: A leader transcription regulatory sequence (TRS-L) usually comprises the first 60-70 nts of the 5' UTR in a CoV genome, and the body transcription regulatory sequences (TRS-Bs) are located immediately upstream of the genes other than ORF1a and 1b. In each CoV genome, the TRS-L and TRS-Bs share a specific consensus sequence, namely the TRS motif. Any changes of nucleotide residues in the TRS motifs are defined as TRS motif mutations. Mutations in the TRS-L or multiple TRS-Bs result in superattenuated variants. The spread of super-attenuated variants may cause an increase in asymptomatic or mild infections, prolonged incubation periods and a decreased detection rate of the viruses, thus posing new challenges to SARS-CoV-2 prevention and control. The super-attenuated variants also increase their possibility of long-term coexistence with humans. The Delta variant is significantly different from all the previous variants and may lead to a large-scale transmission. The Delta variant (B.1.617.2) with TRS motif mutation has already appeared and shown signs of spreading in Singapore, which, and even the Southeast Asia, may become the new epicenter of the next wave of SARS-CoV-2 outbreak. CONCLUSION: TRS motif mutation will occur in all variants of SARS-CoV-2 and may result in super-attenuated variants. Only super-attenuated variants with TRS motif mutations will eventually lose the abilities of cross-species transmission and causing outbreaks.


Subject(s)
COVID-19 , Mutation , SARS-CoV-2 , COVID-19/virology , Genome, Viral , Humans , SARS-CoV-2/genetics
12.
Journal of Planning Literature ; 37(1):204-204, 2022.
Article in English | Web of Science | ID: covidwho-1756135
13.
14.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326814

ABSTRACT

The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social and economic stability. In this study, we established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus S protein and its host receptor ACE2. This platform is a rapid, sensitive, specific, and high throughput system. With this platform, we screened two compound libraries of 2,864 molecules and identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S-protein and the human cell ACE2 receptor. This data suggests that TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

15.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326785

ABSTRACT

The COVID-19 pandemic highlights the need for computational tools to automate and accelerate drug design for novel protein targets.We leverage deep learning language models to generate and score drug candidates based on predicted protein binding affinity. We pre-trained a deep learning language model (BERT) on ~9.6 billion molecules and achieved peak performance of 603 petaflops in mixed precision. Our work reduces pre-training time from days to hours, compared to previous efforts with this architecture, while also increasing the dataset size by nearly an order of magnitude. For scoring, we fine-tuned the language model using an assembled set of thousands of protein targets with binding affinity data and searched for inhibitors of specific protein targets, SARS-CoV-2 Mpro and PLpro. We utilized a genetic algorithm approach for finding optimal candidates using the generation and scoring capabilities of the language model. Our generalizable models accelerate the identification of inhibitors for emerging therapeutic targets.

16.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326746

ABSTRACT

Lethal COVID-19 is associated with respiratory failure that is thought to be caused by acute respiratory distress syndrome (ARDS) secondary to pulmonary infection. To date, the cellular pathogenesis has been inferred from studies describing the expression of ACE2, a transmembrane protein required for SARS-CoV-2 infection, and detection of viral RNA or protein in infected humans, model animals, and cultured cells. To functionally test the cellular mechanisms of COVID-19, we generated hACE2fl animals in which human ACE2 (hACE2) is expressed from the mouse Ace2 locus in a manner that permits cell-specific, Cre-mediated loss of function. hACE2fl animals developed lethal weight loss and hypoxemia within 7 days of exposure to SARS-CoV-2 that was associated with pulmonary infiltrates, intravascular thrombosis and patchy viral infection of lung epithelial cells. Deletion of hACE2 in lung epithelial cells prevented viral infection of the lung, but not weight loss, hypoxemia or death. Inhalation of SARS-CoV-2 by hACE2fl animals resulted in early infection of sustentacular cells with subsequent infection of neurons in the neighboring olfactory bulb and cerebral cortex—events that did not require lung epithelial cell infection. Pharmacologic ablation of the olfactory epithelium or Foxg1Cre mediated deletion of hACE2 in olfactory epithelial cells and neurons prevented lethality and neuronal infection following SARS-CoV-2 infection. Conversely, transgenic expression of hACE2 specifically in olfactory epithelial cells and neurons in Foxg1Cre;LSL-hACE2 mice was sufficient to confer neuronal infection associated with respiratory failure and death. These studies establish mouse loss and gain of function genetic models with which to genetically dissect viral-host interactions and demonstrate that lethal disease due to respiratory failure may arise from extrapulmonary infection of the olfactory epithelium and brain. Future therapeutic efforts focused on preventing olfactory epithelial infection may be an effective means of protecting against severe COVID-19.

17.
18th International Conference on Information Systems for Crisis Response and Management, ISCRAM 2021 ; 2021-May:333-344, 2021.
Article in English | Scopus | ID: covidwho-1589538

ABSTRACT

This research intends to answer: how do (i) generation frequency and (ii) retweeting count of health agencies' messages impact the exposure of the general users to vaccine-related misinformation on Twitter? We creatively employed a Susceptible-Infected-Recovered (SIR) System Dynamics paradigm to model interactions between message dissemination of 168 U.S. health agencies and proportions of users who are at different exposure statuses to misinformation, namely "Susceptible", "Infected", or "Recovered" status. The SIR model was built based on the vaccine-relevant tweets posted over November and December in 2020. Our preliminary outcomes suggest that augmenting the generation frequency of agencies' messages and increasing retweeting count can effectively moderate the exposure risk to vaccine-related misinformation. This model illustrates how health agencies may combat vaccine hesitancy through credible information dissemination on social media. It offers a novel approach for crisis informatics studies to model different information categories and the impacted population in the complex digital world. © 2021 Information Systems for Crisis Response and Management, ISCRAM. All rights reserved.

18.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-297018

ABSTRACT

Lethal COVID-19 is associated with respiratory failure that is thought to be caused by acute respiratory distress syndrome (ARDS) secondary to pulmonary infection. To date, the cellular pathogenesis has been inferred from studies describing the expression of ACE2, a transmembrane protein required for SARS-CoV-2 infection, and detection of viral RNA or protein in infected humans, model animals, and cultured cells. To functionally test the cellular mechanisms of COVID-19, we generated hACE2 fl animals in which human ACE2 (hACE2) is expressed from the mouse Ace2 locus in a manner that permits cell-specific, Cre-mediated loss of function. hACE2 fl animals developed lethal weight loss and hypoxemia within 7 days of exposure to SARS-CoV-2 that was associated with pulmonary infiltrates, intravascular thrombosis and patchy viral infection of lung epithelial cells. Deletion of hACE2 in lung epithelial cells prevented viral infection of the lung, but not weight loss, hypoxemia or death. Inhalation of SARS-CoV-2 by hACE2 fl animals resulted in early infection of sustentacular cells with subsequent infection of neurons in the neighboring olfactory bulb and cerebral cortexa" events that did not require lung epithelial cell infection. Pharmacologic ablation of the olfactory epithelium or Foxg1 Cre mediated deletion of hACE2 in olfactory epithelial cells and neurons prevented lethality and neuronal infection following SARS-CoV-2 infection. Conversely, transgenic expression of hACE2 specifically in olfactory epithelial cells and neurons in Foxg1 Cre ;LSL- hACE2 mice was sufficient to confer neuronal infection associated with respiratory failure and death. These studies establish mouse loss and gain of function genetic models with which to genetically dissect viral-host interactions and demonstrate that lethal disease due to respiratory failure may arise from extrapulmonary infection of the olfactory epithelium and brain. Future therapeutic efforts focused on preventing olfactory epithelial infection may be an effective means of protecting against severe COVID-19.

19.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294885

ABSTRACT

The novel coronavirus disease, named COVID-19, emerged in China in December 2019, and has rapidly spread around the world. It is clearly urgent to fight COVID-19 at global scale. The development of methods for identifying drug uses based on phenotypic data can improve the efficiency of drug development. However, there are still many difficulties in identifying drug applications based on cell picture data. This work reported one state-of-the-art machine learning method to identify drug uses based on the cell image features of 1024 drugs generated in the LINCS program. Because the multi-dimensional features of the image are affected by non-experimental factors, the characteristics of similar drugs vary greatly, and the current sample number is not enough to use deep learning and other methods are used for learning optimization. As a consequence, this study is based on the supervised ITML algorithm to convert the characteristics of drugs. The results show that the characteristics of ITML conversion are more conducive to the recognition of drug functions. The analysis of feature conversion shows that different features play important roles in identifying different drug functions. For the current COVID-19, Chloroquine and Hydroxychloroquine achieve antiviral effects by inhibiting endocytosis, etc., and were classified to the same community. And Clomiphene in the same community inibited the entry of Ebola Virus, indicated a similar MoAs that could be reflected by cell image.

20.
Journal of Contemporary Chinese Art ; 8(2-3):267-289, 2021.
Article in English | Web of Science | ID: covidwho-1542207

ABSTRACT

With the impact of the COVID-19 outbreak, much of the world has been experiencing isolation and quarantine. Digital technology, especially the internet, has become the essential method of communication when social distancing measures constrain physical contact. The global health crisis leads to a dynamically increasing reliance on digital equipment contributing to a posthuman world. The article will take Shanghai-based multimedia artist Lu Yang (1984-) as a representative example to explore an alternative posthumanism subjectivity in the context of the COVID-19 pandemic. Built theoretically on Kathrine Hayles and Rosi Braidotti's posthumanism concepts of virtual bodies, this article will examine how Lu Yang's work articulates the interactive relationships between humans and the material world to go beyond the conservative corporeality and contribute to a renewal of posthuman subjectivity. In Lu Yang's recent projects created during the pandemic, such as Doku x The 1975 'Playing on My Mind' (2020) and the live-streamed piece Delusional World specialIntscript the artist experiments with different strategies to break down social-cultural constraints and transcend established dualisms of gender binaries, life and death, human and non-human. With a close investiga-tion of Lu Yang's multidisciplinary artistic practices, this article intends to argue how a new subjectivity emerges in contemporary Chinese art and its roles in the current COVID-19 pandemic world.

SELECTION OF CITATIONS
SEARCH DETAIL