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<title>12 August, 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>Additive Manufacturing Leveraged Microfluidic Setup for Sample to Answer Colorimetric Detection of Pathogens</strong> -
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<div>
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Colorimetric readout for the detection of infectious diseases is gaining traction at the point of care/need owing to its ease of analysis and interpretation, and integration potential with highly specific Loop-mediated amplification (LAMP) assays. However, coupling colorimetric readout with LAMP is rife with challenges including, rapidity, inter-user variability, colorimetric signal quantification, and user involvement in sequential steps of the LAMP assay, hindering its application. To address these challenges, for the first time, we propose a remotely smartphone-operated automated setup consisting of (i) an additively manufactured microfluidic cartridge, (ii) a portable reflected-light imaging setup with controlled epi-illumination (PRICE) module, and (iii) a control and data analysis module. The microfluidic cartridge facilitates sample collection, lysis, mixing of amplification reagents stored on-chip, and subsequent isothermal heating for initiation of amplification in a novel way by employing tunable elastomeric chambers and auxiliary components (heaters and linear actuators). PRICE offers a new imaging setup that captures the colorimetric change of the amplification media over a plasmonic nanostructured substrate in a controlled and noise-free environment for rapid minute-scale nucleic acid detection. The control and data analysis module employs microprocessors to automate cartridge operation in tandem with the imaging module. The different device components were characterized individually and finally, as a proof of concept, SARS-CoV-2 wild-type RNA was detected with a turnaround time of 13 minutes, showing the clinical feasibility. The suggested automated device can be adopted in future iterations for other detection and molecular assays that require sequential fluid handling steps.
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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/10.1101/2023.08.10.552726v1" target="_blank">Additive Manufacturing Leveraged Microfluidic Setup for Sample to Answer Colorimetric Detection of Pathogens</a>
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</div></li>
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<li><strong>Pretrainable Geometric Graph Neural Network for Antibody Affinity Maturation</strong> -
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<div>
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In the realm of antibody therapeutics development, increasing the binding affinity of an antibody to its target antigen is a crucial task. This paper presents GearBind, a pretrainable deep neural network designed to be effective for in silico affinity maturation. Leveraging multi-level geometric message passing alongside contrastive pretraining on protein structural data, GearBind capably models the complex interplay of atom-level interactions within protein complexes, surpassing previous state-of-the-art approaches on SKEMPI v2 in terms of Pearson correlation, mean absolute error (MAE) and root mean square error (RMSE). In silico experiments elucidate that pretraining helps GearBind become sensitive to mutation-induced binding affinity changes and reflective of amino acid substitution tendency. Using an ensemble model based on pretrained GearBind, we successfully optimize the affinity of CR3022 to the spike (S) protein of the SARS-CoV-2 Omicron strain. Our strategy yields a high success rate with up to 17-fold affinity increase. GearBind proves to be an effective tool in narrowing the search space for in vitro antibody affinity maturation, underscoring the utility of geometric deep learning and adept pre-training in macromolecule interaction modeling.
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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/10.1101/2023.08.10.552845v1" target="_blank">Pretrainable Geometric Graph Neural Network for Antibody Affinity Maturation</a>
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</div></li>
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<li><strong>Waning of post-vaccination neutralizing antibody responses against SARS-CoV-2, a systematic literature review and meta-analysis</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background Mass COVID-19 vaccination and the continuous introduction of new viral variants of SARS-CoV-2, especially of Omicron subvariants, has resulted in an increase in the proportion of the population with hybrid immunity at various stages of waning protection. We systematically reviewed waning of post-vaccination neutralizing antibody titers in different immunological settings to investigate potential differences. Methods We searched for studies providing data for post-vaccination neutralizing antibody responses against SARS-CoV-2 in PubMed, bioRxiv, and medRxiv from Dec 15, 2021, to Jan 31, 2023, using keywords related to COVID-19, vaccination, and antibody neutralization. We used random effects meta-regression to estimate the average fold-reduction in post-vaccination neutralizing antibody titers against the Index strain or Omicron BA.1. from month 1 to month 6 post last dose, stratified by vaccination regimen (primary or booster) and infection-naive vs hybrid-immune status. Findings In total, 26 studies reporting longitudinal post-vaccination neutralizing antibody titers were included. Neutralization titers against the Index variant were available from all studies for infection-naive participants, and from nine for hybrid-immune participants. Against Omicron BA.1, nine and eight studies were available for infection-naive and hybrid-immune cohorts, respectively. In infection-naive cohorts, post-vaccination neutralization titers against the Index strain waned 5.1-fold (95% CI 3.4-7.8) from month 1 to month 6 following primary regimen and 3.8-fold (95% CI 2.4-5.9) following the booster. Titers against Omicron BA.1 waned 5.9-fold (95% CI 3.8-9.0) in infection-naive, post-booster cohorts. In hybrid-immune, post-primary vaccination cohorts, titers waned 3.7-fold (95% CI 1.7-7.9) against the Index strain and 5.0-fold (95% CI 1.1-21.8) against Omicron BA.1. Interpretation No obvious differences in waning between post-primary or post-boost vaccination were observed for vaccines used widely to date, nor between infection-naive and hybrid-immune participants. Titers against Omicron BA.1 may wane faster compared to Index titers, which may worsen for more recent Omicron sub-variants and should be monitored. Relatively small datasets limit the precision of our current analysis; further investigation is needed when more data become available. However, based on our current findings, striking differences in waning for the analyzed and future comparisons are unlikely.
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</p>
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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.medrxiv.org/content/10.1101/2023.08.08.23293864v1" target="_blank">Waning of post-vaccination neutralizing antibody responses against SARS-CoV-2, a systematic literature review and meta-analysis</a>
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</div></li>
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<li><strong>Iterative In Silico Screening for Optimizing Stable Conformation of Anti-SARS-CoV-2 Nanobodies</strong> -
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<div>
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Abstract–Nanobodies (Nbs or VHHs) are single-domain antibodies (sdAbs) derived from camelid heavy-chain antibodies. The variable region of these nanobodies has special and unique characteristics, such as small size, good tissue penetration, and cost-effective production, making nanobodies a good candidate for the diagnosis and treatment of viruses. Identifying effective nanobodies against the COVID-19 would help us defeat this dangerous virus or other unknown variants in future. Herein, we introduce an in silico screening strategy for optimizing stable conformation of anti-SARS-CoV-2 nanobodies. Firstly, various complexes containing nanobodies were downloaded from the RCSB database, which were identified from immunized llamas. The primary docking between nanobodies and the SARS-CoV-2 spike protein receptor-binding domain was performed through ClusPro program, with the manually screening that leaving the reasonable conformation to the next step. Then, the binding distances of atoms between the antigen-antibody interfaces was measured through the Neighbor Search algorithm. Finally, filtered nanobodies were acquired according to HADDOCK scores through HADDOCK docking the Covid spike protein with nanobodies under restrictions of calculated molecular distance between active residues and antigenic epitopes less than 4.5 A. In this way, those nanobodies which with more reasonable conformation and with stronger neutralizing efficacy were acquired. This three-steps screening strategy iteratively in Silico greatly improved the accuracy of screening desired nanobodies compared to using only ClusPro docking or default HADDOCK docking settings. It provides new ideas for the screening of novel antibodies and computer-aided screening methods.
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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/10.1101/2023.08.09.552633v1" target="_blank">Iterative In Silico Screening for Optimizing Stable Conformation of Anti-SARS-CoV-2 Nanobodies</a>
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</div></li>
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<li><strong>Development and Analytical Evaluation of a Point-of-Care Electrochemical Biosensor for Rapid and Accurate SARS-CoV-2 Detection</strong> -
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<div>
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The COVID-19 pandemic has underscored the critical need for rapid and accurate screening and diagnostic methods for potential respiratory viruses. Existing COVID-19 diagnostic approaches face limitations either in terms of turnaround time or accuracy. In this study, we present an electrochemical biosensor that offers nearly instantaneous and precise SARS-CoV-2 detection, suitable for point-of-care and environmental monitoring applications. The biosensor employs a stapled hACE-2 N-terminal alpha helix peptide to functionalize an in-situ grown polypyrrole conductive polymer on a nitrocellulose membrane backbone through a chemical process. We assessed the biosensor's analytical performance using heat-inactivated omicron and delta variants of the SARS-CoV-2 virus in artificial saliva (AS) and nasal swabs (NS) samples diluted in a strong ionic solution. Virus identification was achieved through electrochemical impedance spectroscopy (EIS) and frequency analyses. The assay demonstrated a limit of detection of 40 TCID50/mL, with 95% sensitivity and 100% specificity. Notably, the biosensor exhibited no cross-reactivity when tested against the influenza virus. The entire testing process using the biosensor takes less than a minute. In summary, our biosensor exhibits promising potential in the battle against pandemic respiratory viruses, offering a platform for the creation of rapid, compact, portable, and point-of-care devices capable of multiplexing various viruses. This groundbreaking development has the capacity to significantly bolster our readiness and response to future viral outbreaks.
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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/10.1101/2023.08.08.552470v1" target="_blank">Development and Analytical Evaluation of a Point-of-Care Electrochemical Biosensor for Rapid and Accurate SARS-CoV-2 Detection</a>
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</div></li>
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<li><strong>Enhanced Deep Convolutional Neural Network for SARS-CoV-2 Variants Classification</strong> -
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<div>
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High-throughput sequencing techniques and sequence analysis have enabled the taxonomic classification of pathogens present in clinical samples. Sequencing provides an unbiased identification and systematic classification of pathogens and this is generally achieved by comparing novel sequences to pre-existing annotated reference databases. However, this approach is limited by large-scale reference databases which require considerable computational resources and skills to compare against. Alternative robust methods such as machine learning are currently employed in genome sequence analysis and classification, and it can be applied in classifying SARS-CoV-2 variants, whose continued evolution has resulted in the emergence of multiple variants. We developed a deep learning Convolutional Neural Networks-Long Short Term Memory (CNN-LSTM) model to classify dominant SARS-CoV-2 variants (omicron, delta, beta, gamma and alpha) based on gene sequences from the surface glycoprotein (spike gene). We trained and validated the model using > 26,000 SARS-CoV-2 sequences from the GISAID database. The model was evaluated using unseen 3,057 SARS-CoV-2 sequences. The model was compared to existing molecular epidemiology tool, nextclade. Our model achieved an accuracy of 98.55% on training, 99.19% on the validation and 98.41% on the test dataset. Comparing the proposed model to nextclade, the model achieved significant accuracy in classifying SARS-CoV-2 variants from unseen data. Nextclade identified the presence of recombinant strains in the evaluation data, a mechanism that the proposed model did not detect. This study provides an alternative approach to pre-existing methods employed in the classification of SARS-CoV-2 variants. Timely classification will enable effective monitoring and tracking of SARS-CoV-2 variants and inform public health policies in the control and management of the COVID-19 pandemic.
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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/10.1101/2023.08.09.552643v1" target="_blank">Enhanced Deep Convolutional Neural Network for SARS-CoV-2 Variants Classification</a>
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</div></li>
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<li><strong>Open-source milligram-scale, four channel, automated protein purification system</strong> -
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<div>
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Liquid chromatography purification of multiple recombinant proteins, in parallel, could catalyze research and discovery if the processes are fast and approach the robustness of traditional, "one-protein-at-a-time" purification. Here, we report an automated, four channel chromatography platform that we have designed and validated for parallelized protein purification at milligram scales. The device can purify up to four proteins (each with its own single column), has inputs for up to eight buffers or solvents that can be directed to any of the four columns via a network of software-driven valves, and includes an automated fraction collector with ten positions for 1.5 or 5.0 mL collection tubes and four positions for 50 mL collection tubes for each column output. The control software can be accessed either via Python scripting, giving users full access to all steps of the purification process, or via a simple-to-navigate touch screen graphical user interface that does not require knowledge of the command line or any programming language. Using our instrument, we report milligram-scale, parallelized, single-column purification of a panel of mammalian cell expressed coronavirus (SARS-CoV-2, HCoV-229E, HCoV-OC43, HCoV-229E) trimeric Spike and monomeric Receptor Binding Domain (RBD) antigens, and monoclonal antibodies targeting SARS-CoV-2 Spike (S) and Influenza Hemagglutinin (HA). We include a detailed hardware build guide, and have made the controlling software open source, to allow others to build and customize their own protein purifier systems.
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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/10.1101/2023.08.09.552685v1" target="_blank">Open-source milligram-scale, four channel, automated protein purification system</a>
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</div></li>
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<li><strong>Parental intention, attitudes, beliefs, trust and deliberation towards childhood vaccination in the Netherlands in 2022: Indications of change compared to 2013</strong> -
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<div>
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<b>Background and aim</b> Vaccine uptake within the Dutch National Immunisation Programme (NIP) has slightly declined since the COVID-19 pandemic. We studied psychosocial factors of vaccine uptake, namely parental intention, attitudes, beliefs, trust and deliberation (i.e. self-evidence), before (2013) and two years into the pandemic (2022). <b>Methods</b> In 2022 and 2013, parents with a young child (aged <3.5 years) participated in online surveys on vaccination (n=1,000 and 800, (estimated) response=12.2% and 37.2%, respectively). Psychosocial factors were measured on 7-point Likert scales. Multivariate logistic regression analysis was used to study differences between parents in 2022 and 2013 in 9negative9 scores (≤2) of psychosocial factors. <b>Results</b> In both 2022 and 2013, most parents with a young child expressed positive intention (2022=83.1%, 2013=87.0%), attitudes (3 items: 2022=66.7%-70.9%, 2013=62.1%-69.8%) and trust (2022=51.8%, 2013=52.0%) towards the NIP and felt that vaccinating their child was self-evident (2022=57.2%, 2013=67.3%). Compared to parents with a young child in 2013, parents with a young child in 2022 had significantly higher odds of reporting negative attitudes towards vaccination (3 items combined: OR=2.84), believing that vaccinations offer insufficient protection (OR=4.89), that the NIP is not beneficial for the protection of their child9s health (OR=2.23), that vaccinating their child does not necessarily protect the health of other children (OR=2.24) or adults (OR=2.22) and that vaccinations could cause severe side effects (OR=2.20), preferring natural infection over vaccination (OR=3.18) and reporting low trust towards the NIP (OR=1.73). <b>Conclusions</b> Although most parents had positive intention, attitudes and trust towards vaccination and perceived vaccinating their child as self-evident, proportions of parents with negative scores were slightly larger in 2022 compared to 2013. Monitoring these determinants of vaccine uptake and developing appropriate interventions could contribute to sustaining high vaccine uptake.
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</p>
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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.medrxiv.org/content/10.1101/2023.07.24.23291934v2" target="_blank">Parental intention, attitudes, beliefs, trust and deliberation towards childhood vaccination in the Netherlands in 2022: Indications of change compared to 2013</a>
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<li><strong>Contact patterns of older adults with and without frailties in the Netherlands during the COVID-19 pandemic</strong> -
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Background During the COVID-19 pandemic social distancing measures were imposed to protect the population from exposure, especially older adults and persons with frailties who have the highest risk for severe outcomes. These restrictions greatly reduced contacts in the general population, but little is known about behaviour changes among older adults and persons with frailties themselves. Our aim was to quantify how COVID-19 measures affected contact behaviour of older adults and how this differed between older adults with and without frailties. Methods In 2021 a contact survey was carried out among persons aged 70 years and older in the Netherlands. A random sample of persons per age group (70-74, 75-79, 80-84, 85-89, 90+) and gender was invited to participate, either during a period with stringent (April 2021) or moderate (October 2021) measures. Participants provided general information on themselves including their frailty, and they reported characteristics of all persons with whom they had face-to-face contact on a given day over the course of a full week. Results In total 720 community-dwelling elderly persons were included (overall response rate of 15%), who reported 16,505 contacts. During the survey period with moderate measures, participants without frailties had significantly more contacts outside their household than participants with frailties. Especially for females, frailty was a more informative predictor for number of contacts than age. During the survey period with stringent measures, participants with and without frailties had significantly lower numbers of contacts compared to the survey period with moderate measures. The reduction of number of contacts was largest for the eldest participants without frailties. As they interact mostly with adults of a similar high age who likely have frailties, this reduction of number of contacts indirectly protects older adults with frailties from SARS-CoV-2 exposure. Conclusions The results of this study reveal that social distancing measures during the COVID-19 pandemic differentially affected the contact patterns of older adults with and without frailties. The reduction of contacts may have led to direct protection of older adults in general but also to indirect protection of older adults with frailties.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.09.23289550v2" target="_blank">Contact patterns of older adults with and without frailties in the Netherlands during the COVID-19 pandemic</a>
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<li><strong>An Energizing Role for Motivation in Information-Seeking During the Early Phase of the COVID- 19 Pandemic</strong> -
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<div>
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Curiosity is a powerful determinant of behavior. The past decade has seen a surge of scientific research on curiosity, an endeavor recently imbibed with urgency by the WHO, which set managing information-seeking as a public health goal during pandemics. And yet, a fundamental aspect of curiosity has remained unresolved: its relationship to utility. Is curiosity a drive towards information simply for the sake of obtaining that information, or is it a rational drive towards optimal learning? We leveraged people’s curiosity about COVID-19 to study information-seeking and learning in a large sample (n=5376) during the spring of 2020. Our findings reveal that curiosity is goal-rational in that it maximizes the personal utility of learning. Personal utility, unlike normative economic utility, is contingent on a person’s motivational state. On the basis of these findings, we explain information-seeking during the pandemic with a rational theoretical framework for curiosity.
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</div>
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🖺 Full Text HTML: <a href="https://psyarxiv.com/hcta4/" target="_blank">An Energizing Role for Motivation in Information-Seeking During the Early Phase of the COVID- 19 Pandemic</a>
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<li><strong>Verification Theatre at Borders and in Pockets</strong> -
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To appear in: Colleen M. Flood, Y.Y. Brandon Chen, Raywat Deonandan, Sam Halabi, and Sophie Thériault (eds.) Pandemics, Public Health, and the Regulation of Borders: Lessons from COVID-19 (Routledge, forthcoming). This version: August 2023. Abstract The COVID-19 pandemic saw the creation of a wide array of digital infrastructures, underpinning both digital and paper systems, for proving attributes such as vaccination, test results or recovery. These systems were hotly debated. Yet this debate often failed to connect their social, technical and legal aspects, focussing on one area to the exclusion of the others. In this paper, I seek to bring them together. I argue that fraud-free “vaccination certificate” systems were a technical and social pipe-dream, but one that was primarily advantageous to organisations wishing to establish and own infrastructure for future ambitions as verification platforms. Furthermore, attempts to include features to ostensibly reduce fraud had, and risks further, broader knock-on effects on local digital infrastructures around the world, particularly in countries with low IT capacities easily captured by large firms and de facto excluded from and by global standardisation processes. The paper further reflects on the role of privacy in these debates, and how privacy, and more specifically confidentiality, was misconstrued as a main design aim of these systems, when the main social problems could manifest even in a system built with state of the art privacy-enhancing technologies. The COVID-19 pandemic should sharpen our senses towards the importance of infrastructures, and more broadly, how to use technologies in societies in crises.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/h24uv/" target="_blank">Verification Theatre at Borders and in Pockets</a>
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<li><strong>Transformative Effects of COVID-19 on Healthcare Systems</strong> -
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The global healthcare landscape has undergone an unprecedented metamorphosis due to the COVID-19 pandemic, revealing vulnerabilities, sparking innovation, and necessitating adaptive strategies. This crisis’s impact extends beyond immediate health concerns, influencing healthcare delivery, policy, and infrastructure. Healthcare systems faced overwhelming strain, resulting in improvised medical units and resource allocation shifts. The pandemic prompted the deferral of non-urgent medical procedures, while telehealth integration surged, reshaping patient-doctor interactions. Fragile supply chains underscored the need for enhanced resilience measures. Mental health challenges highlighted the importance of comprehensive care, and healthcare workers exhibited remarkable resilience. Collective efforts accelerated scientific advancements, yielding swift vaccine development. Existing health inequalities were exacerbated, underscoring the urgency of equitable healthcare provision. Policy reforms and global cooperation played pivotal roles. A paradigm shift emerged, emphasizing digital innovation in healthcare. The pandemic’s repercussions underscore the significance of adaptability, collaboration, and ensuring fair access to care.
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🖺 Full Text HTML: <a href="https://osf.io/8x53a/" target="_blank">Transformative Effects of COVID-19 on Healthcare Systems</a>
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<li><strong>Cell cycle regulation of the psoriasis associated gene CCHCR1 by transcription factor E2F1</strong> -
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The coiled-coil alpha-helical rod protein 1 (CCHCR1) was first identified as a candidate gene in psoriasis and has lately been associated with COVID-19 susceptibility. Located within P-bodies and centrosomes, its exact cellular role and transcriptional control remain largely unknown. Here, we showed that CCHCR1 shares a bidirectional promoter with its neighboring gene, TCF19. This bidirectional promoter is activated by the G1/S-regulatory transcription factor E2F1, and both genes are co-induced during the G1/S transition of the cell cycle. A luciferase reporter assay suggests that the short intergenic sequence, only 287 bp in length, is sufficient for the G1/S induction of both genes, but the expression of CCHCR1 is further enhanced by the presence of exon 1 from both TCF19 and CCHCR1. This research uncovers the transcriptional regulation of the CCHCR1 gene, offering new perspectives on its function. These findings contribute to the broader understanding of diseases associated with CCHCR1 and may serve as a foundational step for future research in these vital medical fields.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.08.535951v3" target="_blank">Cell cycle regulation of the psoriasis associated gene CCHCR1 by transcription factor E2F1</a>
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<li><strong>In silico thermodynamic evaluation of the effectiveness of RT-LAMP primers to SARS-CoV-2 variants detection</strong> -
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Viral mutations are the primary cause of mismatches in primer-target hybridisation, affecting the sensibility of molecular techniques, potentially leading to detection dropouts. Despite its importance, little is known about the quantitative effect of mismatches in primer-target hybridisation. We use up-to-date and highly detailed thermodynamic model parameters of DNA mismatches to evaluate the sensibility to variants of SARS-CoV-2 RT-LAMP primers. We aligned 18 RT-LAMP primer sets, which were underwent clinical validation, to the genomes of Wuhan strain (ws), 7 variants and 4 subvariants, and calculated hybridisation temperatures allowing up to three consecutive mismatches. We calculate the coverage when the mismatched melting temperature falls by more than 5C in comparison to the matched alignments. If no mismatches are considered, the average coverage found would be 94% for ws, falling the lowest value for Omicron: 84%. However, considering mismatches the coverage is much higher: 97% (ws) to 88% (Omicron). Stabilizing mismatches (higher melting temperatures), account for roughly 1/3 of this increase. The number of primer dropouts increases for new each variant, however the effect is much less severe if mismatches are considered. We suggest using melting temperature calculations to continuously assess the trend of primer dropouts.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.08.552530v1" target="_blank">In silico thermodynamic evaluation of the effectiveness of RT-LAMP primers to SARS-CoV-2 variants detection</a>
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<li><strong>Heart-on-a-chip model of immune-induced cardiac dysfunction reveals the involvement of free mitochondrial DNA and therapeutic effects of endothelial exosomes</strong> -
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Cardiovascular disease continues to take more human lives than all cancer combined, prompting the need for improved research models and treatment options. Despite a significant progress in development of mature heart-on-a-chip models of fibrosis and cardiomyopathies starting from induced pluripotent stem cells (iPSCs), human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip system with circulating immune cells to model SARS-CoV-2-induced acute myocarditis. Briefly, we observed hallmarks of COVID-19-induced myocardial inflammation in the heart-on-a-chip model, as the presence of immune cells augmented the expression levels of proinflammatory cytokines, triggered progressive impairment of contractile function and altered intracellular calcium transient activities. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the in vitro heart-on-a-chip model and then validated in COVID-19 patients with low left ventricular ejection fraction (LVEF), demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2 induced myocardial inflammation, we established that administration of human umbilical vein-derived EVs effectively rescued the contractile deficit, normalized intracellular calcium handling, elevated the contraction force and reduced the ccf- mtDNA and chemokine release via TLR-NF-kB signaling axis.
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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/10.1101/2023.08.09.552495v1" target="_blank">Heart-on-a-chip model of immune-induced cardiac dysfunction reveals the involvement of free mitochondrial DNA and therapeutic effects of endothelial exosomes</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</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>A Phase 2/3 Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose of Previously Vaccinated Participants.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: XBB.1.5 Vaccine (Booster); Biological: XBB.1.5 Vaccine (single dose)<br/><b>Sponsor</b>: Novavax<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 Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: Freeze-dried Mare Milk (Saumal)<br/><b>Sponsor</b>: Asfendiyarov Kazakh National Medical 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>EFFECT OF COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: rehacom<br/><b>Sponsor</b>: Cairo University<br/><b>Enrolling by invitation</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>Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly</strong> - <b>Conditions</b>: Vaccination; Infection; COVID-19<br/><b>Intervention</b>: Biological: Comirnaty<br/><b>Sponsor</b>: Radboud University Medical Center<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 Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: mRNA-CR-04 vaccine 10μg; Biological: mRNA-CR-04 vaccine 30μg; Biological: mRNA-CR-04 vaccine 100μg; Drug: Placebo<br/><b>Sponsor</b>: GlaxoSmithKline<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>Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine; Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)<br/><b>Sponsor</b>: Novavax<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>Hyperbaric on Pulmonary Functions in Post Covid -19 Patients.</strong> - <b>Condition</b>: Post COVID-19 Patients<br/><b>Interventions</b>: Device: hyperbaric oxygen therapy; Device: breathing exercise; Drug: medical treatment<br/><b>Sponsor</b>: Cairo University<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>Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Fatigue<br/><b>Interventions</b>: Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome; Other: Attention Control<br/><b>Sponsor</b>: University of Maryland, Baltimore<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 II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19</strong> - <b>Conditions</b>: SARS CoV 2 Infection; Influenza, Human<br/><b>Interventions</b>: Biological: BIMERVAX; Biological: SIIV<br/><b>Sponsor</b>: Hipra Scientific, S.L.U<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>Directed Topical Drug Delivery for Treatment for PASC Hyposmia</strong> - <b>Condition</b>: Post Acute Sequelae Covid-19 Hyposmia<br/><b>Interventions</b>: Drug: Beclomethasone; Other: Placebo; Device: Microsponge<br/><b>Sponsor</b>: Duke 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>Supported Employment COVID-19 Rapid Testing for PWID</strong> - <b>Condition</b>: Health Behavior<br/><b>Intervention</b>: Behavioral: Supported Employment<br/><b>Sponsor</b>: University of Oregon<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>Telerehabilitation for Post COVID-19 Condition</strong> - <b>Conditions</b>: Long COVID; Chronic Fatigue Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program based on cardiorespiratory principles<br/><b>Sponsors</b>: Université de Sherbrooke; Hotel Dieu Hospital<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>Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19</strong> - <b>Condition</b>: Coronavirus Infections<br/><b>Interventions</b>: Drug: tixagevimab/cilgavimab 150+150 mg; Drug: tixagevimab/cilgavimab 300+300 mg; Drug: regdanvimab<br/><b>Sponsors</b>: City Clinical Hospital No.52 of Moscow Healthcare Department; Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation<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>Immunogenicity and Safety of Concomitant Administration of Bivalent COVID-19 Vaccines With Influenza Vaccines</strong> - <b>Conditions</b>: Immune Response; Safety<br/><b>Interventions</b>: Biological: bivalent BNT162b2 mRNA original/omicron BA.4-5 vaccine; Biological: quadrivalent influenza vaccine<br/><b>Sponsors</b>: Catholic Kwandong University; Korea University Guro 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>Getting INFORMED and Living Well Among Asian Americans in California</strong> - <b>Conditions</b>: COVID-19; Well-Being, Psychological<br/><b>Interventions</b>: Behavioral: INFORMED-Living Well; Behavioral: Text Messaging Only<br/><b>Sponsors</b>: University of California, San Francisco; Chinese Community Health Resource Center; University of California, Davis; University of California, Merced; California Department of Public Health<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>Mechanism and antibacterial synergies of poly(Dabco-BBAC) nanoparticles against multi-drug resistant Pseudomonas aeruginosa isolates from human burns</strong> - Multi-drug resistant bacteria are a major problem in the treatment of infectious diseases, such as pneumonia, meningitis, or even coronavirus disease 2019 (COVID-19). Cationic nanopolymers are a new type of antimicrobial agent with high efficiency. We synthesized and characterized cationic polymer based on 1,4-diazabicyclo [2.2.2] octane (DABCO) and Bis (bromoacetyl)cystamine (BBAC), named poly (DABCO-BBAC) nanoparticles(NPs), and produced 150 nm diameter NPs. The antibacterial activity of poly…</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>Targeting RdRp of SARS-CoV-2 with De Novo Molecule Generation</strong> - Viruses are known for their extremely high mutation rates, allowing them to evade both the human immune system and many forms of standard medicine. Despite this, the RNA dependent RNA polymerase (RdRp) of the RNA viruses has been largely conserved, and any significant mutation of this protein is unlikely. The recent COVID-19 pandemic presents a need for therapeutics. We have designed a de novo drug design algorithm that generates strong binding ligands from scratch, based on only the structure…</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>Regadenoson for the treatment of COVID-19: A five case clinical series and mouse studies</strong> - CONCLUSIONS: Infused RA is safe and produces rapid anti-inflammatory effects mediated by A2A adenosine receptors on iNKT cells and possibly in part by A2ARs on other immune cells and platelets. We speculate that iNKT cells are activated by release of injury-induced glycolipid antigens and/or alarmins such as IL-33 derived from virally infected type II epithelial cells which in turn activate iNKT cells and secondarily other immune cells. Adenosine released from hypoxic tissues, or RA infused as…</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>Shedding light into the biological activity of aminopterin, <em>via</em> molecular structural, docking, and molecular dynamics analyses</strong> - In this study, the structural and anticancer properties of aminopterin, as well as its antiviral characteristics, were elucidated. The preferred conformations of the title molecule were investigated with semiempirical AM1 method, and the obtained the lowest energy conformer was then optimized by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies of the optimized structure were calculated by the same level of theory and were compared with 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>Soluble wild-type ACE2 molecules inhibit newer SARS-CoV-2 variants and are a potential antiviral strategy to mitigate disease severity in COVID-19</strong> - SARS-CoV-2, the virus responsible for COVID-19, has caused havoc around the world. While several COVID-19 vaccines and drugs have been authorised for use, these antiviral drugs remain beyond the reach of most low- and middle-income countries. Rapid viral evolution is reducing the efficacy of vaccines and monoclonal antibodies and contributing to deaths of some fully vaccinated persons. Others with normal immunity may have chosen not be vaccinated and remain at risk if they contract 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><em>In vitro</em> and <em>in vivo</em> effects of <em>Pelargonium sidoides DC.</em> root extract EPs<sup>®</sup> 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2</strong> - The occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPs^(®) 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lung cells. Here we assessed in vivo effects of EPs^(®) 7630 in SARS-CoV-2-infected hamsters, and investigated properties of EPs^(®) 7630 and its functionally relevant constituents in context of…</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>Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression</strong> - The G-quadruplex (G4) formed in single-stranded DNAs or RNAs plays a key role in diverse biological processes and is considered as a potential antiviral target. In the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 25 putative G4-forming sequences are predicted; however, the effects of G4-binding ligands on SARS-CoV-2 replication have not been studied in the context of viral infection. In this study, we investigated whether G4-ligands suppressed SARS-CoV-2 replication…</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>Author Correction: Cell-impermeable staurosporine analog targets extracellular kinases to inhibit HSV and SARS-CoV-2</strong> - No abstract</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 Toll-like receptor 4 and Interleukin-1 receptor prevent SARS-CoV-2 mediated kidney injury</strong> - Acute kidney injury (AKI) is a common and severe complication of the coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly affects the glomerular and tubular epithelial cells to induce AKI; however, its pathophysiology remains unclear. Here, we explored the underlying mechanisms and therapeutic targets of renal involvement in COVID-19. We developed an in vitro human kidney cellular model, including immortalized tubular epithelial and…</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>PRO-2000 exhibits SARS-CoV-2 antiviral activity by interfering with spike-heparin binding</strong> - Here, we report on the anti-SARS-CoV-2 activity of PRO-2000, a sulfonated polyanionic compound. In Vero cells infected with the Wuhan, alpha, beta, delta or omicron variant, PRO-2000 displayed EC(50) values of 1.1 μM, 2.4 μM, 1.3 μM, 2.1 μM and 0.11 μM, respectively, and an average selectivity index (i.e. ratio of cytotoxic versus antiviral concentration) of 172. Its anti-SARS-CoV-2 activity was confirmed by virus yield assays in Vero cells, Caco2 cells and A549 cells overexpressing ACE2 and…</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>Diketo acid inhibitors of nsp13 of SARS-CoV-2 block viral replication</strong> - For RNA viruses, RNA helicases have long been recognized to play critical roles during virus replication cycles, facilitating proper folding and replication of viral RNAs, therefore representing an ideal target for drug discovery. SARS-CoV-2 helicase, the non-structural protein 13 (nsp13) is a highly conserved protein among all known coronaviruses, and, at the moment, is one of the most explored viral targets to identify new possible antiviral agents. In the present study, we present six diketo…</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>Heterologous vaccination (ChAdOx1 and BNT162b2) induces a better immune response against the omicron variant than homologous vaccination</strong> - CONCLUSION: In conclusion, our findings suggest that heterologous booster vaccination after primary vaccination produces higher nAb titers and provides a higher level of protection against the omicron variant compared to primary vaccination alone. This protective effect was similar to that observed in patients with severe COVID-19.</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 Systematic Survey of Reversibly Covalent Dipeptidyl Inhibitors of the SARS-CoV-2 Main Protease</strong> - SARS-CoV-2, the COVID-19 pathogen, relies on its main protease (M^(Pro)) for replication and pathogenesis. M^(Pro) is a demonstrated target for the development of antivirals for SARS-CoV-2. Past studies have systematically explored tripeptidyl inhibitors such as nirmatrelvir as M^(Pro) inhibitors. However, dipeptidyl inhibitors especially those with a spiro residue at their P2 position have not been systematically investigated. In this work, we synthesized about 30 dipeptidyl M^(Pro) inhibitors…</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>Observing inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution</strong> - The genome of SARS-CoV-2 encodes for a helicase (nsp13) that is essential for viral replication and highly conserved across related viruses, making it an attractive antiviral target. Here we use nanopore tweezers, a high-resolution single-molecule technique, to gain detailed insight into how nsp13 turns ATP-hydrolysis into directed motion along nucleic acid strands. We measured nsp13 both as it translocates along single-stranded DNA or unwinds double-stranded DNA. Our data reveal nsp13’s…</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>Greener approach for the isolation of oleanolic acid from <em>Nepeta leucophylla Benth</em>. Its derivatization and their molecular docking as antibacterial and antiviral agents</strong> - In the present study bioactive methanolic extract along with chloroform and hexane extracts obtained from shade dried leaves of the Himalayan aromatic medicinal plant Nepeta leucophylla Benth. Were screened for the presence of triterpenoids, especially oleanolic acid (OA). Total three compounds oleanolic acid, squalene and linoleic methyl ester were isolated from methanol extract. The percentage yield of OA was 0.11%. Out of these three, OA is more bioactive and was further subjected to…</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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