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<title>17 December, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Structure of a SARS-CoV-2 spike S2 subunit in a pre-fusion, open conformation</strong> -
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<div>
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The 800 million human infections with SARS-CoV-2 and the likely emergence of new variants and additional coronaviruses necessitate a better understanding of the essential spike glycoprotein and the development of immunogens that foster broader and more durable immunity. The S2 fusion subunit is more conserved in sequence, is essential to function, and would be a desirable immunogen to boost broadly reactive antibodies. It is, however, unstable in structure and in its wild-type form, cannot be expressed alone without irreversible collapse into a six-helix bundle. In addition to the irreversible conformational changes of fusion, biophysical measurements indicate that spike also undergoes a reversible breathing action. However, spike in an open, -breathing- conformation has not yet been visualized at high resolution. Here we describe an S2-only antigen, engineered to remain in its relevant, pre-fusion viral surface conformation in the absence of S1. We also describe a panel of natural human antibodies specific for S2 from vaccinated and convalescent individuals. One of these mAbs, from a convalescent individual, afforded a high-resolution cryo-EM structure of the prefusion S2. The structure reveals a complex captured in an -open- conformation with greater stabilizing intermolecular interactions at the base and a repositioned fusion peptide. Together, this work provides an antigen for advancement of next-generation -booster- immunogens and illuminates the likely breathing adjustments of the coronavirus spike.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.14.571764v1" target="_blank">Structure of a SARS-CoV-2 spike S2 subunit in a pre-fusion, open conformation</a>
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</div></li>
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<li><strong>SARS-CoV-2 and other coronaviruses in rats, Berlin, Germany, 2023</strong> -
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<div>
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We tested 130 rats trapped in Berlin for coronaviruses. Antibodies against SARS-CoV-2 were detected in a single animal only, but not in further 66 rats from the same location, speaking against virus circulation in the rat population. All animals tested negative for SARS-CoV-2 by RT-PCR. However, rodent-associated alphacoronaviruses were found.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.15.571826v1" target="_blank">SARS-CoV-2 and other coronaviruses in rats, Berlin, Germany, 2023</a>
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</div></li>
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<li><strong>“Life would have been harder, harder and more in chaos, if there wasn’t internet”: Digital Inclusion among Newly Arrived Refugees in Australia during the Covid-19 Pandemic</strong> -
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<div>
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Globally we are living through a continuing transition into the ‘information age’, where information and communication technology has transformed almost every aspect of people’s lives. The COVID-19 pandemic arguably accelerated this change. For refugees, as with other people, digital inclusion is arguably critical to social inclusion. This article seeks to better understand the digital inclusion of refugees during the COVID-19 pandemic, using data from two phases of research conducted in 2020 and 2021 with refugees who had recently resettled in Australia. Digital inclusion was mapped against three domains – access, affordability, and literacy – used in the annual Australian Digital Inclusion Index. Our research makes three contributions: it examines levels of digital inclusion among recently arrived refugees; it explores the relation of these levels to social links and bonds; and discusses differences within the sample according to gender, age, language group and type of digital inclusion.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/nqu8c/" target="_blank">“Life would have been harder, harder and more in chaos, if there wasn’t internet”: Digital Inclusion among Newly Arrived Refugees in Australia during the Covid-19 Pandemic</a>
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</div></li>
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<li><strong>How Generative AI Portrays Science. Interviewing ChatGPT from the Perspective of Different Audience Segments</strong> -
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<div>
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Generative AI in general and ChatGPT in particular have risen in importance. ChatGPT is widely known and used increasingly as an information source for different topics, including science. It is therefore relevant how ChatGPT portrays science and science-related topics. Research on this question is lacking, however. Hence, we “interview” ChatGPT and reconstruct how it presents science, scientists, scientific misbehavior and controversial scientific fields. Combining qualitative and quantitative content analysis, we find that, generally, ChatGPT portrays science largely as the STEM disciplines, in a positivist-empiricist way and a positive light. We compare ChatGPT’s responses to different simulated user profiles and two versions of GPT and find similarities in that the scientific consensus on questions like climate change, COVID-19 vaccinations or astrology is consistently conveyed across them. Beyond these similarities in substance, however, pronounced differences are found in the personalization of responses to different user profiles and between GPT-3.5 and GPT-4.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/erf36/" target="_blank">How Generative AI Portrays Science. Interviewing ChatGPT from the Perspective of Different Audience Segments</a>
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</div></li>
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<li><strong>A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia</strong> -
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<div>
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Pathogen clearance and resolution of inflammation in patients with pneumonia require an effective local T cell response. Nevertheless, local T cell activation may drive lung injury, particularly during prolonged episodes of respiratory failure characteristic of severe SARS-CoV-2 pneumonia. While T cell responses in the peripheral blood are well described, the evolution of T cell phenotypes and molecular signatures in the distal lung of patients with severe pneumonia caused by SARS-CoV-2 or other pathogens is understudied. Accordingly, we serially obtained 432 bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia and respiratory failure, including 74 unvaccinated patients with COVID-19, and performed flow cytometry, transcriptional, and T cell receptor profiling on sorted CD8+ and CD4+ T cell subsets. In patients with COVID-19 but not pneumonia secondary to other pathogens, we found that early and persistent enrichment in CD8+ and CD4+ T cell subsets correlated with survival to hospital discharge. Activation of interferon signaling pathways early after intubation for COVID-19 was associated with favorable outcomes, while activation of NF-{kappa}B-driven programs late in disease was associated with poor outcomes. Patients with SARS-CoV-2 pneumonia whose alveolar T cells preferentially targeted the Spike and Nucleocapsid proteins tended to experience more favorable outcomes than patients whose T cells predominantly targeted the ORF1ab polyprotein complex. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize patients who recover, yet these responses progress to NF-{kappa}B activation against non-structural proteins in patients who go on to experience poor clinical outcomes.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.13.571479v1" target="_blank">A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia</a>
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</div></li>
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<li><strong>Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level</strong> -
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<div>
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It is widely accepted that m6A exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduce Scm6A, a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6A trans regulators and cis sequence features, and found that Scm6A offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we applied a winscore-based m6A calculation method to conduct m6A-seq analysis on CD4+ and CD8+ T-cells isolated through magnetic-activated cell sorting (MACS). Subsequently, we employed Scm6A for analysis on the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with m6A quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6A's reliability. Additionally, we performed single-cell level m6A analysis on lung cancer tissues as well as blood samples from COVID-19 patients, and demonstrated the landscape and regulatory mechanisms of m6A in different T-cell subtypes from these diseases. In summary, our work has yielded a novel, dependable, and accurate method for single-cell m6A detection. We are confident that Scm6A have broad applications in the realm of m6A-related research.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.14.571511v1" target="_blank">Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level</a>
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</div></li>
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<li><strong>Inactivation of the Niemann Pick C1 cholesterol transporter 1 (NPC1) restricts SARS-CoV-2 infection</strong> -
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<div>
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The Niemann Pick C1 (NPC1) protein is an intracellular cholesterol transporter located in the late endosome/lysosome (LE/Ly) and is involved in cholesterol mobilization. Loss-of-function mutations of the NPC1 gene lead to accumulation of cholesterol and sphingolipids in LE/Ly, resulting in severe fatal NPC1 disease. Cellular alterations associated with NPC1 inactivation affect both the integrity of lipid rafts and the endocytic pathway. Because the angiotensin-converting enzyme 2 (ACE2) and type 2 serine transmembrane protease (TMPRSS2) of the SARS-CoV-2 Spike (S) protein also localize to lipid rafts, we sought to investigate the hypothesis that NPC1 inactivation would generate an intrinsically unfavorable barrier to SARS-CoV-2 entry. In this study, we demonstrate that NPC1 pharmacological inactivation or CRISP/R-Cas mediated ablation of NPC1 dramatically reduced SARS-CoV-2 infectivity. More specifically, our findings demonstrate that pharmacological inactivation of NPC1 results in massive accumulation of ACE2 in the autophagosomal/lysosomal compartment. A >40-fold decrease in virus titer indicates that this effectively prevents VSV-Spike-GFP infection by impeding virus binding and entry. A similarly marked decrease in viral infectivity is observed in cells that had NPC1 expression genetically abrogated. These observations were further confirmed in a de novo SARS-CoV-2 infection paradigm, where cells were infected with the naturally pathogenic SARS-CoV-2. Overall, this work offers strong evidence that NPC1 function is essential for successful SARS-CoV-2 infection, thus implicating NPC1 as a potential therapeutic target in COVID-19 management.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.13.571570v1" target="_blank">Inactivation of the Niemann Pick C1 cholesterol transporter 1 (NPC1) restricts SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Differential outcomes of infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern in K18-hACE2 transgenic mice</strong> -
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<div>
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Background: SARS-CoV-2 is a respiratory virus with neurological complications including loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of Wild-type virus, Delta and Omicron variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lung, brain medulla oblongata and olfactory bulbs of these animals. We hypothesized that Wild-type, Delta and Omicron differentially infect K18-hACE2 mice, thereby inducing distinct cellular responses. Methods: K18-hACE2 female mice were intranasally infected with Wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, olfactory bulbs, medulla oblongata, and brains. Results: Mice infected with Wild-type and Delta display higher levels of viral RNA in the lungs than mice infected with Omicron at 3dpi. Viral RNA levels in the brains of mice infected with the Wild-type virus were however significantly lower than those observed in mice infected with either Delta or Omicron at 3dpi. Viral RNA was also detected in the medulla oblongata of mice infected by all these virus strains at 3dpi. At this time point, mice infected with the Delta virus display a marked upregulation of inflammatory makers both in the lungs and brains. Upregulation of inflammatory markers was also observed in the brains of mice infected with Omicron but not in mice infected with the Wild-type virus, suggesting that during the initial phase of the infection only the Delta and Omicron variants induce strong inflammatory response in the brain. At the humane endpoint/8dpi, mice infected by any of these strains display elevated levels of viral RNA and upregulation of a subset of inflammatory markers in the lungs. There was also a significant increase in viral RNA in the brains of mice infected with Wild-type and Delta, as compared to 3dpi. This was accompanied by an increase in the expression of most cytokines and chemokines. In contrast, mice infected with the Omicron variant showed low levels of viral RNA and downregulation of cytokines and chemokines expression at 8dpi, suggesting that brain inflammation by this variant is attenuated. Reduced RNA levels and downregulation of inflammatory markers was also observed in the medulla oblongata and olfactory bulbs of mice infected with Omicron, while infection by Wild-type and Delta resulted in high levels of viral RNA and increased expression of inflammatory makers in these organs.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556906v2" target="_blank">Differential outcomes of infection by wild-type SARS-CoV-2 and the B.1.617.2 and B.1.1.529 variants of concern in K18-hACE2 transgenic mice</a>
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</div></li>
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<li><strong>Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease</strong> -
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<div>
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Codon optimization describes the process used to increase protein production by use of alternative but synonymous codon changes. In SARS-CoV-2 mRNA vaccines codon optimizations can result in differential secondary conformations that inevitably affect a protein’s function with significant consequences to the cell. Importantly, when codon optimization increases the GC content of synthetic mRNAs, there can be an inevitable enrichment of G-quartets which potentially form G-quadruplex structures. The emerging G-quadruplexes are favorable binding sites of RNA binding proteins like helicases that inevitably affect epigenetic reprogramming of the cell by altering transcription, translation and replication. In this study, we performed a RNAfold analysis to investigate alterations in secondary structures of mRNAs in SARS-CoV-2 vaccines due to codon optimization. We show a significant increase in the GC content of mRNAs in vaccines as compared to native SARS-CoV-2 RNA sequences encoding the spike protein. As the GC enrichment leads to more G-quadruplex structure formations, these may contribute to potential pathological processes initiated by SARS-CoV-2 molecular vaccination.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/bcsa6/" target="_blank">Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease</a>
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</div></li>
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<li><strong>Examining perceptions of stress, wellbeing and fear among Hungarian adolescents and their parents under lockdown during the COVID-19 pandemic</strong> -
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<div>
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Intensified anxiety responses and even symptoms of post-traumatic stress are commonly observed under quarantine conditions. In this study, the effects on fear, anxiety and wellbeing of the recent pandemic caused by SARS-CoV-2 were investigated in a sample of otherwise healthy Hungarians. Taking the family as a microsystem, differences in gender, age, family relationships and time spent in isolation were the main focus of this investigation. 346 parent-child dyads were examined; the children were 11-17 years of age. Standard psychological questionnaires (Perceived Stress Scale, WHO Wellbeing Index), and an open question test (the Metamorphosis test) were used, and the results analysed with the aid of basic statistical methods. Stress levels and wellbeing displayed a significant negative correlation with each other in both parents and children. Parental stress and levels of wellbeing had a weak but significant impact on the wellbeing of their children. Among the demographic variables examined, none of them was found to explain the wellbeing or stress level of parents. Natural catastrophes, such as pandemics, create a stressful social environment for parents, and therefore directly impact the psychological wellbeing of all family members.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/feth3/" target="_blank">Examining perceptions of stress, wellbeing and fear among Hungarian adolescents and their parents under lockdown during the COVID-19 pandemic</a>
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<li><strong>Acceptability and feasibility of a theatre-based wellness programme to support people living with Long COVID: a single arm feasibility study.</strong> -
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Objectives: To determine acceptability and feasibility of a theatre-based wellness programme to support the health and wellbeing of people with long COVID. Design: Single group, repeated measures feasibility study. Setting: Community centre and online. Participants: Adults with a diagnosis of long COVID experiencing breathlessness, mild to moderate pain, and/or loneliness. Intervention: A six-week participatory creative intervention delivered to two groups of participants, one online and one in-person. The groups were facilitated by movement, voice and drama consultants and designed to improve wellbeing, fatigue, pain, strength and balance through a series of breathing exercises, visualisation, group singing and sound imagery, storytelling, movement exercises and poetry. Primary outcome measures: Acceptability of the intervention and feasibility of recruitment procedures and data collection. Secondary outcome measures: Changes in mental health, wellbeing, quality of life, loneliness, social support, fatigue, breathlessness, and post-COVID-19 functional status. Results: 20 participants took part in the intervention, 19 completed baseline assessments and 16 completed study follow-up. Most participants found the programme acceptable and feasible and improvements were identified in all outcomes at 8-week follow-up, including decreases in generalised anxiety and depressive symptoms, loneliness, shortness of breath, respiratory dysfunction, chronic fatigue and increased mental wellbeing, social support, and self-rated health. Key programme features and mechanisms of action that led to improvements in health and wellbeing were identified in qualitative interviews. Barriers to engagement included: activities being outside of the participant’s comfort zone, ongoing and fluctuating long COVID symptoms, emotional consequences of sharing experiences with the group and connectivity and connecting with others online. Conclusions: A six-week theatre-based programme was perceived as acceptable to most participants and resulted in positive psychosocial impacts. The findings provide a rationale for supporting the ongoing development of this and related programmes and for scaling up research into arts programmes to support people living with long COVID.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/k25qj/" target="_blank">Acceptability and feasibility of a theatre-based wellness programme to support people living with Long COVID: a single arm feasibility study.</a>
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<li><strong>Artificial Intelligence and Robotics for Reducing Waste in the Food Supply Chain: Systematic Literature Review, Theoretical Framework, and Research Agenda</strong> -
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The COVID-19 pandemic has unraveled the inefficiencies in the global food supply chain. One glaring distortion is the wastage of close to a third of global food production, in the face of widespread food insecurity. With population explosion and climate change as additional pressure points, reducing food waste has emerged as an urgent imperative for achieving food security for all. In this paper, we develop a research framework and agenda for the use of Artificial Intelligence and robotics in reducing food loss and waste. The Cognitive Automation for Food (COGAF) has been developed as a theoretical framework for guiding future research. This framework delineates the research landscape into five distinct research streams: sensory enhancement, cognitive automation, physical automation, sensory-motor fusion, and collaborative automation. In order to develop a systematic research agenda, propositions have been developed in each of these research streams. In conjunction with the COGAF framework, this research agenda attempts to provide a road map for future research and knowledge creation pertaining to the use of AI and robotics to reduce food loss and waste.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/h3jgb/" target="_blank">Artificial Intelligence and Robotics for Reducing Waste in the Food Supply Chain: Systematic Literature Review, Theoretical Framework, and Research Agenda</a>
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<li><strong>Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform</strong> -
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Biological evidence suggests ursodeoxycholic acid (UDCA) - a common treatment of cholestatic liver disease - may prevent severe COVID-19 outcomes. With the approval of NHS England, we conducted a population-based cohort study using primary care records, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. We estimated the hazard of COVID-19 hospitalisation or death between 1 March 2020 and 31 December 2022, comparing UDCA treatment to no UDCA treatment in a population with indication. Of 11,320 eligible individuals, 642 were hospitalised or died with COVID-19 during follow-up, 402 (63%) events among UDCA users. After confounder adjustment, UDCA was associated with a 21% (95% CI 7%-33%) relative reduction in the hazard of COVID-19 hospitalisation or death, consistent with an absolute risk reduction of 1.3% (95% CI 1.0%-1.6%). Our findings support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.11.23299191v1" target="_blank">Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform</a>
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<li><strong>A software tool for at-home measurement of sensorimotor adaptation</strong> -
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<div>
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Sensorimotor adaptation is traditionally studied in well-controlled laboratory settings with specialized equipment. However, recent public health concerns such as the COVID-19 pandemic, as well as a desire to recruit a more diverse study population, have led the motor control community to consider at-home study designs. At-home motor control experiments are still rare because of the requirement to write software that can be easily used by anyone on any platform. To this end, we developed software that runs locally on a personal computer. The software provides audiovisual instructions and measures the ability of the subject to control the cursor in the context of visuomotor perturbations. We tested the software on a group of at-home participants and asked whether the adaptation principles inferred from in-lab measurements were reproducible in the at-home setting. For example, we manipulated the perturbations to test whether there were changes in adaptation rates (savings and interference), whether adaptation was associated with multiple timescales of memory (spontaneous recovery), and whether we could selectively suppress subconscious learning (delayed feedback, perturbation variability) or explicit strategies (limited reaction time). We found remarkable similarity between in-lab and at-home behaviors across these experimental conditions. Thus, we developed a software tool that can be used by research teams with little or no programming experience to study mechanisms of adaptation in an at-home setting.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.571359v1" target="_blank">A software tool for at-home measurement of sensorimotor adaptation</a>
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<li><strong>Identification of an allele-specific transcription factor binding interaction that regulates PLA2G2A gene expression</strong> -
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<div>
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The secreted phospholipase A2 (sPLA2) isoform, sPLA2-IIA, has been implicated in a variety of diseases and conditions, including bacteremia, cardiovascular disease, COVID-19, sepsis, adult respiratory distress syndrome, and certain cancers. Given its significant role in these conditions, understanding the regulatory mechanisms impacting its levels is crucial. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs), including rs11573156, that are associated with circulating levels of sPLA2-IIA. Through Genotype-Tissue Expression (GTEx), 234 expression quantitative trait loci (eQTLs) were identified for the gene that encodes for sPLA2-IIA, PLA2G2A. SNP2TFBS (https://ccg.epfl.ch/snp2tfbs/) was utilized to ascertain the binding affinities between transcription factors (TFs) to both the reference and alternative alleles of identified SNPs. Subsequently, ChIP-seq peaks highlighted the TF combinations that specifically bind to the SNP, rs11573156. SP1 emerged as a significant TF/SNP pair in liver cells, with rs11573156/SP1 interaction being most prominent in liver, prostate, ovary, and adipose tissues. Further analysis revealed that the upregulation of PLA2G2A transcript levels through the rs11573156 variant was affected by tissue SP1 protein levels. By leveraging an ordinary differential equation, structured upon Michaelis-Menten enzyme kinetics assumptions, we modeled the PLA2G2A transcription's dependence on SP1 protein levels, incorporating the SNP's influence. Collectively, these data strongly suggest that the binding affinity differences of SP1 for the different rs11573156 alleles can influence PLA2G2A expression. This, in turn, can modulate sPLA2-IIA levels, impacting a wide range of human diseases.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.571290v1" target="_blank">Identification of an allele-specific transcription factor binding interaction that regulates PLA2G2A gene expression</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Restoring Energy With Sub-symptom Threshold Optimized Rehabilitation Exercise for Long COVID</strong> - <b>Conditions</b>: Long Covid19; Exercise Intolerance, Riboflavin-Responsive <br/><b>Interventions</b>: Behavioral: Restoring Energy with Sub-symptom Threshold Aerobic Rehabilitation Exercise; Behavioral: Light Stretching/Breathing Exercises <br/><b>Sponsors</b>: Columbia University; New York University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Study of Liraglutide (A Weight Loss Drug) in High Risk Obese Participants With Cognitive and Memory Issues</strong> - <b>Conditions</b>: Multiple Sclerosis; Long COVID; Long Covid19; Obese; Obesity; Obesity, Morbid; Acute Leukemia in Remission <br/><b>Interventions</b>: Drug: Liraglutide Pen Injector [Saxenda]; Other: Medication Diary <br/><b>Sponsors</b>: University of Chicago <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>EXERCISE TRAINING USING AN APP ON PHYSICAL CARDIOVASCULAR FUNCTION INDIVIDUALS WITH POST-COVID-19 SYNDROME</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise; Behavioral: Control <br/><b>Sponsors</b>: University of Nove de Julho <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1 Trial of Recombinant COVID-19 Trivalent Protein Vaccine （CHO Cell）LYB002V14 in Booster Vaccination</strong> - <b>Conditions</b>: SARS-CoV-2; COVID-19 Vaccine <br/><b>Interventions</b>: Biological: 30μg dose of LYB002V14; Biological: 60μg dose of LYB002V14; Biological: placebo <br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Vaccine Effectiveness Against Recurrent Infection Among Lung Cancer Patients and Biomarker Research</strong> - <b>Conditions</b>: COVID-19 Recurrent; Lung Cancer; Vaccination; Antibody; Chemotherapy; Immune Checkpoint Inhibitor <br/><b>Interventions</b>: Biological: Any Chinese government-recommended COVID-19 booster vaccine <br/><b>Sponsors</b>: Peking Union Medical College Hospital <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS.</strong> - <b>Conditions</b>: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation <br/><b>Interventions</b>: Dietary Supplement: Nutritional blend (ImmuneRecov). <br/><b>Sponsors</b>: Federal University of São Paulo <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Physical Activity Coaching in Patients With Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active <br/><b>Sponsors</b>: University of Alcala; Professional College of Physiotherapists of the Community of Madrid <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training</strong> - <b>Conditions</b>: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer <br/><b>Interventions</b>: Device: breathing training <br/><b>Sponsors</b>: Tri-Service General Hospital <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID</strong> - <b>Conditions</b>: Long COVID; Post Acute Sequelae of COVID-19; Post-Acute COVID-19 <br/><b>Interventions</b>: Drug: Ensitrelvir; Other: Placebo <br/><b>Sponsors</b>: Timothy Henrich; Shionogi Inc. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Low-intensity Aerobic Training Associated With Global Muscle Strengthening in Post-COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Procedure: muscle strengthening <br/><b>Sponsors</b>: Centro Universitário Augusto Motta <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Intravenous Immunoglobulin Replacement Therapy for Persistent COVID-19 in Patients With B-cell Impairment</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: Immunoglobulins <br/><b>Sponsors</b>: Jaehoon Ko <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Inhaled Hydroxy Gas on Long COVID Symptoms</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Device: Hydroxy gas <br/><b>Sponsors</b>: Oxford Brookes University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community Care Intervention to Decrease COVID-19 Vaccination Inequities</strong> - <b>Conditions</b>: COVID-19 Vaccination <br/><b>Interventions</b>: Behavioral: Community Health Worker Intervention to Enhance Vaccination Behavior (CHW-VB) <br/><b>Sponsors</b>: RAND; Clinical Directors Network; National Institute on Minority Health and Health Disparities (NIMHD) <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PROmotion of COVID-19 BOOSTer VA(X)Ccination in the Emergency Department - PROBOOSTVAXED</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Vaccine Messaging; Behavioral: Vaccine Acceptance Question <br/><b>Sponsors</b>: University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Duke University; Baylor College of Medicine; Thomas Jefferson University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pursuing Reduction in Fatigue After COVID-19 Via Exercise and Rehabilitation (PREFACER): A Randomized Feasibility Trial</strong> - <b>Conditions</b>: Long-COVID; Long Covid19; Post-COVID-19 Syndrome; Post-COVID Syndrome; Fatigue <br/><b>Interventions</b>: Other: COVIDEx <br/><b>Sponsors</b>: Lawson Health Research Institute; Western University <br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Design, synthesis and biological evaluation of betulinic acid derivatives as potential inhibitors of 3CL-protease of SARS-CoV-2</strong> - During the coronavirus reproduction process, 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are accountable for the fragmentation of two polyprotein precursors (pp1a/pp1ab) into substructural proteins. These two proteins are vital for the replication and transcription of the viral genome. Therefore, 3CLpro is a key protein and target for the design of coronavirus inhibitors. In previous studies, we found that betulinic acid has an inhibitory effect on 3CLpro, with 51.5 %…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Chlorogenic acid inhibits porcine deltacoronavirus release by targeting apoptosis</strong> - Porcine deltacoronavirus (PDCoV), belonging to family Coronaviridae, genus Deltacoronavirus, can cause acute diarrhea in piglets, and also possesses cross-species transmission potential, leading to severe economic losses and threatening public health. However, no approved drug against PDCoV infection is available. Here, we investigated the antiviral effect of chlorogenic acid (CGA), the main active component of Lonicerae Japonicae Flos, against PDCoV infection. The results showed that CGA…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Protective Efficacy of Novel Engineered Human ACE2-Fc Fusion Protein Against Pan-SARS-CoV-2 Infection In Vitro and in Vivo</strong> - Enduring occurrence of severe COVID-19 for unvaccinated, aged, or immunocompromised individuals remains an urgent need. Soluble human angiotensin-converting enzyme 2 (ACE2) has been used as a decoy receptor to inhibit SARS-CoV-2 infection, which is limited by moderate affinity. We describe an engineered, high-affinity ACE2 that is consistently effective in tissue cultures in neutralizing all strains tested, including Delta and Omicron. We also found that treatment of AC70 hACE2 transgenic mice…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>C<sub>60</sub> -based Multivalent Glycoporphyrins Inhibit SARS-CoV-2 Specific Interaction with the DC-SIGN Transmembrane Receptor</strong> - Since WHO has declared the COVID-19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS-CoV-2, other receptors could play a role in viral entry. Among others, C-type lectins such as DC-SIGN are identified as efficient trans-receptor…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DYRK1A is a multifunctional host factor that regulates coronavirus replication in a kinase-independent manner</strong> - Coronaviruses, like other positive-sense RNA viruses, can remodel the host membrane to form double-membrane vesicles (DMVs) as their replication organelles. Currently, host factors involved in DMV formation are not well defined. In this study, we used transmissible gastroenteritis virus (TGEV) as a virus model to investigate the regulatory mechanism of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) on coronavirus. Results showed that DYRK1A significantly inhibited TGEV…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I study, and dosing regimen selection for a pivotal COVID-19 trial of GST-HG171</strong> - This study is aimed to evaluate the safety, tolerability, and pharmacokinetics (PK), as well as to select an appropriate dosing regimen for the pivotal clinical trial of GST-HG171, an orally bioavailable, potent, and selective 3CL protease inhibitor by a randomized, double-blind, and placebo-controlled phase I trial in healthy subjects. We conducted a Ph1 study involving 78 healthy subjects to assess the safety, tolerability, and PK of single ascending doses (150-900 mg) as well as multiple…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Promises and Pitfalls of Calcineurin Inhibitors in COVID-19: A Systematic Review and Meta-analysis of Controlled Trials</strong> - CONCLUSION: CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An overview of the role of Niemann-pick C1 (NPC1) in viral infections and inhibition of viral infections through NPC1 inhibitor</strong> - Viruses communicate with their hosts through interactions with proteins, lipids, and carbohydrate moieties on the plasma membrane (PM), often resulting in viral absorption via receptor-mediated endocytosis. Many viruses cannot multiply unless the host’s cholesterol level remains steady. The large endo/lysosomal membrane protein (MP) Niemann-Pick C1 (NPC1), which is involved in cellular cholesterol transport, is a crucial intracellular receptor for viral infection. NPC1 is a ubiquitous…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Acarbose reduces Pseudomonas aeruginosa respiratory tract infection in type 2 diabetic mice</strong> - CONCLUSIONS: This study confirmed the attenuating effect of acarbose on P. aeruginosa RTIs in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An exonuclease-resistant chain-terminating nucleotide analogue targeting the SARS-CoV-2 replicase complex</strong> - Nucleotide analogues (NA) are currently employed for treatment of several viral diseases, including COVID-19. NA prodrugs are intracellularly activated to the 5’-triphosphate form. They are incorporated into the viral RNA by the viral polymerase (SARS-CoV-2 nsp12), terminating or corrupting RNA synthesis. For Coronaviruses, natural resistance to NAs is provided by a viral 3’-to-5’ exonuclease heterodimer nsp14/nsp10, which can remove terminal analogues. Here, we show that the replacement of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical phenotype and outcome of persistent SARS-CoV-2 replication in immunocompromised hosts: a retrospective observational study in the Omicron era</strong> - CONCLUSION: Ongoing SARS-CoV-2 replication in the lower respiratory tract is a relevant differential diagnosis in patients with severe immunosuppression and continuous cough, fever or dyspnoea even if nasopharyngeal swabs test negative for SARS-CoV-2. Especially in B cell-depleted patients, this may lead to inflammatory or fibrotic-like pulmonary changes, which are partially reversible after inhibition of viral replication. Antiviral therapy seems to be most effective in combination and over a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research</strong> - As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID-19) today, arbidol often involves drug-drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 μL incubation system was used to study the inhibitory…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tumor Treating Fields (TTFields) demonstrate antiviral functions <em>in vitro</em>, and safety for application to COVID-19 patients in a pilot clinical study</strong> - Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing of Rutan showed effective treatment for COVID-19 disease</strong> - Previously, from the tannic sumac plant (Rhus coriaria), we developed the Rutan 25 mg oral drug tablets with antiviral activity against influenza A and B viruses, adenoviruses, paramyxoviruses, herpes virus, and cytomegalovirus. Here, our re-purposing study demonstrated that Rutan at 25, 50, and 100 mg/kg provided a very effective and safe treatment for COVID-19 infection, simultaneously inhibiting two vital enzyme systems of the SARS-CoV-2 virus: 3C-like proteinase (3CLpro) and RNA-dependent…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of the K<sub>Ca</sub>2 potassium channel in atrial fibrillation: a randomized phase 2 trial</strong> - Existing antiarrhythmic drugs to treat atrial fibrillation (AF) have incomplete efficacy, contraindications and adverse effects, including proarrhythmia. AP30663, an inhibitor of the K(Ca)2 channel, has demonstrated AF efficacy in animals; however, its efficacy in humans with AF is unknown. Here we conducted a phase 2 trial in which patients with a current episode of AF lasting for 7 days or less were randomized to receive an intravenous infusion of 3 or 5 mg kg^(-1) AP30663 or placebo. The…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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