- Widespread exposure to SARS-CoV-2 in wildlife communities -
Pervasive SARS-CoV-2 infections in humans have led to multiple transmission events to captive animals. While SARS-CoV-2 has a potential broad wildlife host range, most documented infections to date are found in a single species, the white-tailed deer. The extent of SARS-CoV-2 exposure among wildlife species and the factors that influence wildlife transmission risk remain unknown. We sampled 23 wildlife species for SARS-CoV-2 and examined the effects of urbanization and human use on seropositivity. Here, we document positive detections of SARS-CoV-2 RNA in six species, including the deer mouse, Virginia opossum, raccoon, groundhog, Eastern cottontail, and Eastern red bat. In addition, we found that sites with high human activity had three times higher seroprevalence than low human-use areas. We detected SARS-CoV-2 genomic sequences from nine individuals of six species which were assigned to seven Pango lineages of the Omicron variant. The close match to variants circulating in humans at the time suggests at least seven recent human-to-animal transmission events. Our data support that exposure to SARS-CoV-2 has been widespread in wildlife communities and suggests that areas with high human activity may serve as points of contact for cross-species transmission.
- Impact of crisis communication strategies on peopleās attitudes toward behavioral guidelines regarding COVID-19 and on their trust in local officials -
Introduction: The communication patterns of commercial organizations are generally guided by Situational Crisis Communication Theory (SCCT), but the impact of different crisis communication strategies for public messaging on COVID-19 has not been thoroughly examined. As such, we test how crisis communication strategies affect trust in mayors and the acceptance of behavioral measures, specifically regarding the buffering effect of a mayorās pre-crisis reputation as well whether trust mediates the link between crisis communication strategies and acceptance of behavioral measures. Methods: A total of 561 participants (53% female; mean age 50 yrs) took part in an online experiment in which we systematically manipulated the mayorās crisis communication strategy (deny vs.Ā diminish, vs.Ā rebuild, vs.Ā bolstering, vs.Ā no response) and pre-crisis reputation (good past crisis management, bad past crisis management). Age, gender and education served as covariates. In an exploratory analysis, we also tested the predictive power of personal concern regarding the COVID-19 pandemic as well as internal and external control convictions. Results: In our pre-planned analysis, we found that crisis communication strategies and pre-crisis reputation had no significant effect on participantsā ratings of acceptance of certain behaviors or their behavioral intentions. However, the different communication strategies did affect participantsā trust in the mayor and intention to vote for him. Specifically, we found that while the strategy of denying was overall unsuccessful, all other strategies fared similarly when the mayorās pre-crisis reputation was high. When his pre-crisis reputation was low, differences emerged between the other strategies. The exploratory analysis corroborated earlier findings about the importance of individual concern and trust as predictors of behavioral measures. Discussion: Overall, SCCT seems to be an adequate description the effects of communication strategies on reputation in local officials during a pandemic. Yet, neither direct effects of communication strategies on acceptance of behavioral measures nor indirect effects on behavioral measures could not be shown. Since trust is an important aspect, we advise local officials to carefully choose their communication style.
- Evaluation of The New Student Candidates admission Information System Using ISO/IEC 25010 Model -
During the COVID-19 pandemic, it is very important to pay attention to the evaluation of the quality of higher education information systems because most of internet users were only accessed from home. So it is necessary to evaluate to produce a quality system. This study aimed to evaluate the information system for the candidate of new student admissions at the Muhammadiyah University of Education Sorong. This evaluation was conducted to find out that SIPMB Unimuda Sorong was designed according to the wishes, and how high the level of user satisfaction was. This study used five characteristics that exist in ISO/IE 25010. The results showed that the usability characteristic test obtained a percentage value of 77% in the Very Eligible category. Meanwhile, in testing the functional suitability characteristics, it obtained a score percentage of 98% in the Very Good category. In testing the performance efficiency characteristics, it has met the standard because the average time used is 3.1 seconds for page load, page size is 866 kb, page speed is in Grade C (72%), and Yslow is in grade A (93%) so that we get very good category. The maintainability characteristic test is carried out by taking into account the three test criteria. The test results showed that the system has met the three categories they were instrumentation, consistency, and simplicity, so that SIPMB has met the maintainability test. And testing the reliability characteristics obtained a percentage value of 100%, this shows that SIPMB has met the Telcordia standard. Based on the results of testing and analysis, it can be said that SIPM UNIMUDA Sorong has product quality in accordance with ISO/IEC 25010 Software Product Quality standards.
- Educational Technology in Higher Education on Pandemic Covid-19 Experiences -
The educational technology is very important in the world of education because it can facilitate the process of learning activities both in the classroom and learning activities at home as it is now when learning online or online because of the covid-19 pandemic that spreads throughout the world, including in Indonesia. of learning and learning, the history of the development of educational technology and knowing the meaning of educational technology. The research method used is sourced from secondary data. Secondary data is data obtained from information or knowledge obtained indirectly, among others, includes official documents, books, and research results in the form of reports. The results of this study explain that educational technology has developed steadily where each stage in its development creates a new discovery that facilitates learning activities. The emergence of educational technology makes it easier for educators and students to learn independently and can create the latest innovations in the world of education so that a learning and learning innovation will emerge that makes educators and students able to learn easily and fun.
- Cardiovascular symptoms of PASC are associated with trace-level cytokines that affect the function of human pluripotent stem cell derived cardiomyocytes -
Globally, over 65 million individuals are estimated to suffer from post-acute sequelae of COVID-19 (PASC). A large number of individuals living with PASC experience cardiovascular symptoms (i.e.Ā chest pain and heart palpitations) (PASC-CVS). The role of chronic inflammation in these symptoms, in particular in individuals with symptoms persisting for >1 year after SARS-CoV-2 infection, remains to be clearly defined. In this cross-sectional study, blood samples were obtained from three different sites in Australia from individuals with i) a resolved SARS-CoV-2 infection (and no persistent symptoms i.e.Ā Recovered), ii) individuals with prolonged PASC-CVS and iii) SARS-CoV-2 negative individuals. Individuals with PASC-CVS, relative to Recovered individuals, had a blood transcriptomic signature associated with inflammation. This was accompanied by elevated levels of pro-inflammatory cytokines (IL-12, IL-1beta;, MCP-1 and IL-6) at approximately 18 months post-infection. These cytokines were present in trace amounts, such that they could only be detected with the use of novel nanotechnology. Importantly, these trace-level cytokines had a direct effect on the functionality of pluripotent stem cell derived cardiomyocytes in vitro. This effect was not observed in the presence of dexamethasone. Plasma proteomics demonstrated further differences between PASC-CVS and Recovered patients at approximately 18 months post-infection including enrichment of complement and coagulation associated proteins in those with prolonged cardiovascular symptoms. Together, these data provide a new insight into the role of chronic inflammation in PASC-CVS and present nanotechnology as a possible novel diagnostic approach for the condition.
- scPanel: A tool for automatic identification of sparse gene panels for generalizable patient classification using scRNA-seq datasets -
Single-cell RNA sequencing (scRNA-seq) technologies can generate transcriptomic profiles at a single-cell resolution in large patient cohorts, facilitating discovery of gene and cellular biomarkers for disease. Yet, when the number of biomarker genes is large the translation to clinical applications is challenging due to prohibitive sequencing costs. Here we introduce scPanel, a computational framework designed to bridge the gap between biomarker discovery and clinical application by identifying a sparse gene panel for patient classification from the cell population(s) most responsive to perturbations (e.g., diseases/drugs). scPanel incorporates a data-driven way to automatically determine the minimal number of selected genes. Patient-level classification is achieved by aggregating the prediction probabilities of cells associated with a patient using the area under the curve score. Application of scPanel on scleroderma and COVID-19 datasets resulted in high patient classification accuracy using a small number (<20) of genes automatically selected from the entire transcriptome. We demonstrate 100% cross-dataset accuracy to predict COVID-19 disease state on an external dataset, illustrating the generalizability of the predicted genes. scPanel outperforms other state-of-the-art gene selection methods for patient classification and can be used to identify small sets of reliable biomarker candidates for clinical translation.
- Microgliosis, astrogliosis and loss of aquaporin-4 polarity in frontal cortex of COVID-19 patients -
The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), causing human coronavirus disease 2019 (COVID-19), not only affects the respiratory tract, but also impacts other organs including the brain. A considerable number of COVID-19 patients develop neuropsychiatric symptoms that may linger for weeks and months and contribute to "long-COVID". While the neurological symptoms of COVID-19 are well described, the cellular mechanisms of neurologic disorders attributed to the infection are still enigmatic. Here, we studied the effect of an infection with SARS-CoV-2 on the structure and expression of marker proteins of astrocytes and microglial cells in the frontal cortex of patients who died from COVID-19 in comparison to non-COVID-19 controls. Most of COVID-19 patients had microglial cells with retracted processes and rounded and enlarged cell bodies in both gray and white matter, as visualized by anti-Iba1 staining and confocal fluorescence microscopy. In addition, gray matter astrocytes in COVID-19 patients were frequently labeled by intense anti-GFAP staining, whereas in non-COVID-19 controls, most gray matter astrocytes expressed little GFAP. The most striking difference between astrocytes in COVID-19 patients and controls was found by anti-aquaporin-4 (AQP4) staining. In COVID-19 patients, a large number of gray matter astrocytes showed an increase in AQP4. In addition, AQP4 polarity was lost and AQP4 covered the entire cell, including the cell body and all cell processes, while in controls, AQP4 immunostaining was mainly detected in endfeet around blood vessels and did not visualize the cell body. In summary, our data suggest neuroinflammation upon SARS-CoV-2 infection including microgliosis and astrogliosis, including loss of AQP4 polarity.
- Coatomer complex I is required for the transport of SARS-CoV-2 progeny virions from the endoplasmic reticulum-Golgi intermediate compartment -
SARS-CoV-2 undergoes budding within the lumen of the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and delivers progeny virions to the cell surface by employing vesicular transport. However, the molecular mechanisms remain poorly understood. Using three-dimensional electron microscopic analysis, such as array tomography and electron tomography, we found that virion-transporting vesicles possessed a coated protein on their membrane and demonstrated that the coated protein was coatomer complex I (COPI). During the later stages of SARS-CoV-2 infection, we observed a notable alteration in the distribution of COPI and ERGIC throughout the cytoplasm. Depletion of COPB2, a key component of COPI, led to the confinement of SARS-CoV-2 structural proteins in the perinuclear region, where progeny virions were accumulated within the ERGIC. While the expression levels of viral proteins within cells were comparable, this depletion significantly reduced the efficiency of virion release, leading to the significant inhibition of viral replication. Hence, our findings suggest COPI as a critical player in facilitating the transport of SARS-CoV-2 progeny virions from the ERGIC. Thus, COPI could be a promising target for the development of antivirals against SARS-CoV-2.
- A narrow ratio of nucleic acid to SARS-CoV-2 N-protein enables phase separation -
SARS-CoV-2 Nucleocapsid protein (N) is a viral structural protein that packages the 30kb genomic RNA inside virions and forms condensates within infected cells through liquid-liquid phase separation (LLPS). N, in both soluble and condensed forms, has accessory roles in the viral life cycle including genome replication and immunosuppression. The ability to perform these tasks depends on phase separation and its reversibility. The conditions that stabilize and destabilize N condensates and the role of N-N interactions are poorly understood. We have investigated LLPS formation and dissolution in a minimalist system comprised of N protein and an ssDNA oligomer just long enough to support assembly. The short oligo allows us to focus on the role of N-N interaction. We have developed a sensitive FRET assay to interrogate LLPS assembly reactions from the perspective of the oligonucleotide. We find that N alone can form oligomers but that oligonucleotide enables their assembly into a three-dimensional phase. At a ~1:1 ratio of N to oligonucleotide LLPS formation is maximal. We find that a modest excess of N or of nucleic acid causes the LLPS to break down catastrophically. Under the conditions examined here assembly has a critical concentration of about 1 micromolar. The responsiveness of N condensates to their environment may have biological consequences. A better understanding of how nucleic acid modulates N-N association will shed light on condensate activity and could inform antiviral strategies targeting LLPS.
- Reduced selection during sweeps lead to adaptive momentum on rugged landscapes -
Evolutionary theory seeks to explain the remarkable diversity and adaptability of life on Earth. Current theory offers substantial explanatory power, but it overlooks important transient dynamics that are prominent only when populations are outside equilibrium, such as during selective sweeps. We identify a dynamic that we call "adaptive momentum" whereby lineages with a selective advantage can temporarily sustain more deleterious mutations. This reduction in the strength of purifying selection allows populations to explore fitness valleys that are usually too costly to enter, potentially leading to the discovery of otherwise inaccessible fitness peaks. Using mathematical and agent-based simulations, we demonstrate adaptive momentum and show how periods of disequilibrium become windows of enhanced adaptation. Genetic exploration can occur during these windows without requiring mechanisms such as changing environments or complex landscapes. Adaptive momentum provides a simple potential explanation for bursts of rapid evolution observed in nature, including in pathogens such as SARS-CoV-2 and cancers.
- Deep Learning in Drug Repurposing: A Review of the CoV-DrugX Module within the CoV-DrugX Pipeline -
A comprehensive overview of the integration of deep learning techniques in drug repurposing, particularly focusing on the CoV-DrugX module within the CoV-DrugX Pipeline. The paper highlights the significance of drug repurposing in accelerating treatment discovery, especially in the context of the COVID-19 pandemic. It discusses the emergence of deep learning methods, such as recurrent neural networks (RNNs), graph convolutional networks (GCNs), and long short-term memory (LSTM) networks, in predicting drug-target interactions and identifying repurposable drugs. The review emphasizes the role of deep learning in extracting informative features, improving drug discovery, enhancing drug repositioning, and handling large-scale data effectively. Additionally, it explores the applications and advantages of deep learning in drug repurposing, showcasing its potential to revolutionize the field by learning complex relationships from extensive datasets. The abstract sets the stage for a detailed examination of the DrugX moduleās capabilities within the CoV-DrugX Pipeline, shedding light on its contributions to drug discovery and repurposing efforts, particularly in the fight against COVID-19.
- AI-Driven Drug Repurposing for COVID-19: Revolutionizing Therapeutic Discovery and Treatment Strategies -
In March of 2020, a deadly disaster caused a global pandemic all across the globe. This paper elucidates the concept of drug repurposing, a strategy that harnesses existing drugs for new therapeutic purposes. Leveraging drugs already approved for other indications offers a promising avenue for rapid deployment against COVID-19, circumventing the lengthy and costly process of drug development from scratch. Central to the drug repurposing approach is the utilization of sophisticated computational tools one such development is in the form of CoV-DrugX DL-200 which helps integrate over 200 chemoinformatics properties to analyze drug structures and characteristics and whether or not the drug can be repurposed or not. By accepting input in the form of SMILE structure, canonical SMILE structure, drug name, or DrugBankID, the database employs advanced algorithms to predict the potential candidates. This data-driven approach enables researchers and clinicians to expedite the identification of candidate drugs for clinical trials, accelerating the search for effective therapeutics for the pandemic that was caused and for any other catastrophe that we might face.
- The Challenges of Engaging African American Communities During a Public Health Crisis: The Role of Government Information, COVID-19 Discourse, and Emotional Content on Social Media -
[Forthcoming in International Journal of Strategic Communication] During a public health crisis, social media platforms play a pivotal role in circulating information and influencing public reactions. This research investigates the dynamics of public engagement with COVID-19-related content and government information sources within African American online communities, a population that has experienced significant health risks and inequities. Using advanced computational research methods, we analyzed 199,542 posts from 1,152 communities created between January 2020 and December 2022. The present research focused on the presence of COVID-19-related content, government information sources, the emotions of anger and fear in these posts, and their associations with user engagement metrics. The results indicated that posts discussing COVID-19 and those incorporating government information sources tend to receive lower levels of engagement. On the other hand, posts with higher levels of anger generated more shares and comments. The findings suggest a ātriple disadvantageā in user engagement for social media messages that reference government sources and discuss public health risks without delivering strong negative emotions. These patterns are crucial not only for understanding the challenges faced by the at-risk population but also for aiding researchers and practitioners in developing more effective communication strategies during public health crises.
- A cultural-historical study of affordances for agency when children play in the city environments in Rome -
Children in the Antique Rome showed their agency when playing in the city environment, in other words, the environment afforded them to play and develop their agency. Today, the city is still the same, but childhood is different. We investigated how children play and perform their agency in the city environment today, after the restrictions of Covid19. 60 play episodes were observed by naturalistic observation and analyzed qualitatively. The results show that affordances for agency realized by three distinctive ways, and it also was not performed. The results are useful for childhood and play researchers, educators and playground designers.
- Unravelling the Brexit-COVID-19 Nexus: Assessing the Decline of EU Student Applications into UK Universities -
Whilst the numbers of international students attending UK universities has been increasing in recent years, the 2021/22 and 2022/23 academic years saw a decline in applications from EU domiciled students. This decline is hypothesised to represent a direct result of the end of free movement due to the UKās withdrawal from the European Union (EU), with varying impacts across institutions and study subjects. However, the extent of this decline remains to be estimated and disentangled from the impacts of the COVID-19. Using difference-in-differences in a hierarchical regression framework and Universities and Colleges Admissions Service (UCAS) data, we aim to quantify the decline in the number of student applications post-Brexit. We find evidence of an overall decline of 65 per cent in the 2021 academic year in successful applications from EU students. We note that this decline is more severe for non-Russell Group institutions, and for Health and Life Sciences and Arts and Languages. Further, we explore the spatial heterogeneity of the impact of Brexit across EU countries of origin; seeing the greatest effects for Poland and Germany but that this varies depending on institution type and subject. We are also able to show that higher rates of COVID-19 stringency in the country of origin led to greater applications for UK HE. Our results hold importance for government and institutional policymakers seeking to understand where losses are occurring and how international students respond to external shocks and policy changes. By quantifying the distinct impacts of Brexit and COVID-19, our study offers valuable insights to guide strategic interventions aimed at sustaining the UKās attractiveness as a destination for international students.
Effects of Unsupervised Inspiratory Muscle Training on Ventilation Variability in Post-covid-19 Patients. - Conditions: COVID-19
Interventions: Device: Experimental Group
Sponsors: Universidade Federal do Rio Grande do Norte
Recruiting
A Phase IV Vaccine Study Under the National Cohort Study of Effectiveness and Safety of SARS-CoV-2 (COVID-19) Vaccines. - Conditions: SARS CoV 2 Infection
Interventions: Biological: Johnson & Johnson
Sponsors: Jens D Lundgren, MD; Ministry of the Interior and Health, Denmark
Completed
Detoxification From the Lipid Tract - Conditions: COVID-19 Vaccine Adverse Reaction
Interventions: Device: electroencephalogram biofeedback; Device: electrical brain stimulation; Device: ultra-low frequency transcranial magnetic stimulation; Drug: Sertraline Hydrochloride; Drug: Clonazepam; Drug: Alprazolam; Drug: Metoprolol; Drug: Olanzapine; Drug: Pravastatin Sodium 20 MG; Drug: Sacubitril Valsartan Sodium Hydrate
Sponsors: Pachankis, Yang I., M.D.; First Affiliated Hospital of Chongqing Medical University
Completed
Covid-19 and Influenza Oral Vaccine Study - Conditions: covid19 Infection; Influenza, Human
Interventions: Biological: Covid-19 vaccine; Biological: Influenza vaccine
Sponsors: Vaxine Pty Ltd; Australian Respiratory and Sleep Medicine Institute Ltd
Not yet recruiting
A Study of an Investigational mRNA-1273.815 COVID-19 Vaccine in Previously Vaccinated Adults - Conditions: SARS-CoV-2
Interventions: Biological: Investigational mRNA-1273.815; Biological: Licensed Spikevax Vaccine
Sponsors: ModernaTX, Inc.
Not yet recruiting
A Study of the Efficacy of Troxerutin in Preventing Thrombotic Events in COVID-19 Patients - Conditions: COVID 19 Associated Coagulopathy
Interventions: Drug: Troxerutin; Drug: Placebo; Drug: placebo + low molecular weight heparin; Drug: troxerutin + low molecular weight heparin
Sponsors: Westlake University; Shaoxing Central Hospital
Recruiting
The Use of Isatidis Root and Forsythia Oral Liquid for the Treatment of Mild Cases of COVID-19: A Trial Clinical Study - Conditions: Treatment of Mild Cases of COVID-19
Interventions: Drug: Langenlianqiao; Drug: LianhuaQingWen; Other: placebo control group
Sponsors: Central South University
Completed
Fascial Tissue Response To Manual Therapy: Implications In Long Covid Rehabilitation - Conditions: COVID-19
Interventions: Other: Guidebook; Other: Guidebook and Myofascial ReorganizationĀ® (RMF).
Sponsors: University of the State of Santa Catarina; Larissa Sinhorim
Recruiting
Effect of Probiotic Strain Lactobacillus Paracasei PS23 on Brain Fog in People With Long COVID - Conditions: Long COVID; Brain Fog; Cognitive Change
Interventions: Dietary Supplement: Lactobacillus paracasei PS23; Dietary Supplement: microcrystalline cellulose
Sponsors: Taipei Veterans General Hospital, Taiwan
Not yet recruiting
Evaluation of the Impact of Rehabilitation Strategies and Early Discharge After Respiratory Failure - Conditions: Acute Respiratory Failure
Interventions: Behavioral: Standard of Care; Behavioral: Rehabilitation
Sponsors: Hospital Israelita Albert Einstein
Not yet recruiting
Ivermectin: A Multifaceted Drug With a Potential Beyond Anti-parasitic Therapy - Ivermectin was first discovered in the 1970s by Japanese microbiologist Satoshi Omura and Irish parasitologist William C. Campbell. Ivermectin has become a versatile pharmaceutical over the past 50 years. Ivermectin is a derivative of avermectin originally used to treat parasitic infections. Emerging literature has suggested that its role goes beyond this and may help treat inflammatory conditions, viral infections, and cancers. Ivermectinās anti-parasitic, anti-inflammatory, anti-viral, andā¦
Interleukin inhibitors and the associated risk of candidiasis - Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individualās susceptibility to Candida infections. Variations in the severity ofā¦
New meroterpenoids and polyketides from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1 and their anti-inflammatory and SARS-CoV-2 M(pro) inhibitory activities - Seven new meroterpenoids, paraphaeones A-G (1-7), and two new polyketides, paraphaeones H-I (8-9), along with eight known compounds (10-17), were isolated from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1. The structures of 1-9 were identified through the analysis of Ā¹H, ^(13)C, and 2D NMR spectra, assisted by HR-ESI-MS data. Compounds 1 and 7 exhibited a dose-dependent decrease in lactate dehydrogenase levels, with IC(50) values of 1.78 Ī¼M and 1.54 Ī¼M, respectively. Moreover, theyā¦
Development of a fluorescent scaffold by utilizing quercetin template for selective detection of Hg2+: Experimental and theoretical studies along with live cell imaging - Quercetin is an important antioxidant with high bioactivity and it has been used as SARS-CoV-2 inhibitor significantly. Quercetin, one of the most abundant flavonoids in nature, has been in the spot of numerous experimental and theoretical studies in the past decade due to its great biological and medicinal importance. But there have been limited instances of employing quercetin and its derivatives as a fluorescent framework for specific detection of various cations and anions in theā¦
Storytelling and Deliberative Play in the Oregon Citizensā Assembly Online Pilot on COVID-19 Recovery - This article draws on the deliberative play framework to examine empirical examples of storytelling in an online deliberative forum: The Oregon Citizen Assembly (ORCA) Pilot on COVID-19 Recovery. ORCA engaged 36 citizens in deliberation about state policy through an online deliberative process spanning seven weeks. Drawing on literature on small stories in deliberation, we trace stories related to a policy proposal about paying parents to educate children at home. Our analysis demonstrates thatā¦
Computational identification and experimental verification of a novel signature based on SARS-CoV-2-related genes for predicting prognosis, immune microenvironment and therapeutic strategies in lung adenocarcinoma patients - CONCLUSION: Our research has pioneered the development of a consensus Cov-2S signature by employing an innovative approach with 10 machine learning algorithms for LUAD. Cov-2S reliably forecasts the prognosis, mirrors the tumorās local immune condition, and supports clinical decision-making in tumor therapies.
The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes - INTRODUCTION: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes.
Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera - In response to the urgent need for potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics, this study introduces an innovative nucleoside tailoring strategy leveraging ribonuclease targeting chimeras. By seamlessly integrating ribonuclease L recruiters into nucleosides, we address RNA recognition challenges and effectively inhibit severe acute respiratory syndrome coronavirus 2 replication in human cells. Notably, nucleosides tailored at the ribose 2ā-positionā¦
Interleukin-6 drives endothelial glycocalyx damage in COVID-19 and bacterial sepsis - Damage of the endothelial glycocalyx (eGC) plays a central role in the development of vascular hyperpermeability and organ damage during systemic inflammation. However, the specific signalling pathways for eGC damage remain poorly defined. Aim of this study was to combine sublingual video-microscopy, plasma proteomics and live cell imaging to uncover further pathways of eGC damage in patients with coronavirus disease 2019 (COVID-19) or bacterial sepsis. This secondary analysis of the prospectiveā¦
Laboratory approach for vaccine-induced thrombotic thrombocytopenia diagnosis in the Netherlands - CONCLUSION: Our study shows that only a small proportion of clinically suspected VITT patients with thrombocytopenia and thrombosis have anti-PF4-inducing, FcÉ£RIIa-dependent platelet activation, suggesting an HIT-like pathophysiology. This leaves the possibility for the presence of another type of pathophysiology (ānon-HIT likeā) leading to VITT. More research on pathophysiology is warranted to improve the diagnostic algorithm and to identify novel therapeutic and preventive strategies.
Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model - INTRODUCTION: SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins.
Elderberry interaction with pazopanib in a patient with softātissue sarcoma: A case report and literature review - Elderberry flower extract is marketed as an herbal supplement with purported benefits in boosting the immune system. The use of elderberry increased during the coronavirus pandemic. However, the interaction of elderberry with cytotoxic medicines has remained elusive. Pazopanib is a multikinase inhibitor approved for patients diagnosed with soft-tissue sarcoma. The present study reported on the case of a middle-aged woman diagnosed with localized intermediate-grade sarcoma of the left sartoriusā¦
Efficacy of host cell serine protease inhibitor MM3122 against SARS-CoV-2 for treatment and prevention of COVID-19 - We developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases, including transmembrane protease serine 2 (TMPRSS2), matriptase, and hepsin. TMPRSS2 is a membrane-associated protease that is highly expressed in the upper and lower respiratory tracts and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell entry, replication, and dissemination of new virus particles. We have previously shown thatā¦
Discovery of 2-Amide-3-methylester Thiophenes that Target SARS-CoV-2 Mac1 and Repress Coronavirus Replication, Validating Mac1 as an Antiviral Target - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has made it clear that further development of antiviral therapies will be needed. Here, we describe small-molecule inhibitors for SARS-CoV-2 Mac1, which counters ADP-ribosylation-mediated innate immune responses. Three high-throughput screening hits had the same 2-amide-3-methylester thiophene scaffold. We studied the compound binding mode using X-ray crystallography, allowing us to designā¦
Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics - CONCLUSION: These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.