- 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.
- An Outbreak of Selective Attribution: Partisanship and Blame in the COVID-19 Pandemic -
Crises and disasters give voters an opportunity to observe the incumbentās response and reward or punish them for successes and failures. Yet even when voters perceive events similarly, they tend to attribute responsibility selectively, disproportionately crediting their party for positive developments and blaming opponents for negative developments. We examine selective attribution during the COVID-19 pandemic in the United States, reporting three key findings. First, selective attribution rapidly emerged during the first weeks of the pandemic, a time in which Democrats and Republicans were otherwise updating their perceptions and behavior in parallel. Second, selective attribution is caused by individual-level changes in perceptions of the pandemic. Third, existing research has been too quick to explain selective attribution in terms of partisan-motivated reasoning. We find stronger evidence for an explanation rooted in beliefs about presidential competence. This recasts selective attributionās implications for democratic accountability.
- Public Engagement with COVID-19 Preprints: Bridging the Gap Between Scientists and Society -
The surge in preprint server use, especially during the Covid-19 pandemic, necessitates a reex-amination of their significance in the realm of science communication. This study rigorously investigates discussions surrounding preprints, framing them within the contexts of systems theory and boundary objects in scholarly communication. An analysis of a curated selection of COVID-19-related preprints from bioRxiv and medRxiv was conducted, emphasizing those that transitioned to journal publications, alongside the associated commentary and Twitter activity. The dataset was bifurcated into comments by biomedical experts versus those by non-experts, encompassing both academic and general public perspectives. Findings revealed that while peers dominated nearly half the preprint discussions, their presence in Twitter dia-logues was markedly diminished. Yet, intriguingly, the themes explored by these two groups diverged considerably. Preprints emerged as potent boundary objects, reinforcing, rather than obscuring, the delineation between scientific and non-scientific discourse. They serve as cru-cial conduits for knowledge dissemination and foster inter-disciplinary engagements. None-theless, the interplay between scientists and the wider public remains nuanced, necessitating strategies to incorporate these diverse discussions into the peer review continuum without compromising academic integrity and to cultivate sustained engagement from both experts and the broader community.
- Psychological distance to science as a predictor of science skepticism across domains -
The current paper presents and tests psychological distance to science (PSYDISC) as a domain-general predictor of science skepticism. Drawing on the concept of psychological distance, PSYDISC reflects the extent to which individuals perceive science as a tangible undertaking conducted by people similar to oneself (social), with effects in the here (spatial) and now (temporal), and as useful and applicable in the real world (hypothetical distance). In six studies (2 preregistered; total N = 1,630) and two countries, we developed and established the factor structure and validity of a scale measuring PSYDISC. Crucially, higher PSYDISC predicted skepticism beyond established predictors, across science domains. A final study showed that PSYDISC shapes real-world behavior (COVID-19 vaccination uptake). The current work thus provides a novel tool to predict science skepticism, as well as a construct that can help to further develop a unifying framework to understand science skepticism across domains.
- GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern -
Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 s of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how the structural role of this glycan changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
- Rapid and specific detection of single nanoparticles and viruses in microfluidic laminar flow via confocal fluorescence microscopy -
Mainstream virus detection relies on the specific amplification of nucleic acids via polymerase chain reaction, a process that is slow and requires extensive laboratory expertise and equipment. Other modalities, such as antigen-based tests, allow much faster virus detection but have reduced sensitivity. In this study, we report the development of a flow virometer for the specific and rapid detection of single nanoparticles based on confocal microscopy. The combination of laminar flow and multiple dyes enable the detection of correlated fluorescence signals, providing information on nanoparticle volumes and specific chemical composition properties, such as viral envelope proteins. We evaluated and validated the assay using fluorescent beads and viruses, including SARS-CoV-2. Additionally, we demonstrate how hydrodynamic focusing enhances the assay sensitivity for detecting clinically-relevant virus loads. Based on our results, we envision the use of this technology for clinically relevant bio-nanoparticles, supported by the implementation of the assay in a portable and user-friendly setup.
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.