167 lines
47 KiB
HTML
167 lines
47 KiB
HTML
|
<!DOCTYPE html>
|
|||
|
|
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
|
|||
|
|
<meta charset="utf-8"/>
|
|||
|
|
<meta content="pandoc" name="generator"/>
|
|||
|
|
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
|
|||
|
|
<title>06 March, 2024</title>
|
|||
|
|
<style>
|
|||
|
|
code{white-space: pre-wrap;}
|
|||
|
|
span.smallcaps{font-variant: small-caps;}
|
|||
|
|
span.underline{text-decoration: underline;}
|
|||
|
|
div.column{display: inline-block; vertical-align: top; width: 50%;}
|
|||
|
|
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
|
|||
|
|
ul.task-list{list-style: none;}
|
|||
|
|
</style>
|
|||
|
|
<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>
|
|||
|
|
<body>
|
|||
|
|
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
|
|||
|
|
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li><a href="#from-preprints">From Preprints</a></li>
|
|||
|
|
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
|
|||
|
|
<li><a href="#from-pubmed">From PubMed</a></li>
|
|||
|
|
<li><a href="#from-patent-search">From Patent Search</a></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li><strong>Yeast-based production platform for potent and stable heavy chain-only antibodies</strong> -
|
|||
|
|
<div>
|
|||
|
|
Monoclonal antibodies are the leading drug of the biopharmaceutical market because of their high specificity and tolerability, but the current CHO-based manufacturing platform remains expensive and time-consuming leading to limited accessibility, especially in the case of diseases with high incidence and pandemics. Therefore, there is an urgent need for an alternative production system. In this study, we present a rapid and cost-effective microbial platform for heavy chain-only antibodies (VHH-Fc) in the methylotrophic yeast Komagataella phaffii (aka Pichia pastoris). We demonstrate the potential of this platform using a simplified single-gene VHH-Fc fusion construct instead of the conventional monoclonal antibody format, as this is more easily expressed in Pichia pastoris. We demonstrate that the Pichia-produced VHH-Fc fusion construct is stable and that a Pichia-produced VHH-Fc directed against the SARS-CoV-2 spike has potent SARS-CoV-2 neutralizing activity in vitro and in vivo. We expect that this platform will pave the way towards faster and cheaper development and production of broadly neutralizing single-chain antibodies in yeast.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.04.580093v1" target="_blank">Yeast-based production platform for potent and stable heavy chain-only antibodies</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Filopodial Mechanotransduction is regulated by Angiotensin-Converting Enzyme 2 (ACE2) and by SARS-CoV-2 spike protein</strong> -
|
|||
|
|
<div>
|
|||
|
|
Filopodia are dynamic, actin-rich cellular protrusions, increasingly linked to cellular mechanotransduction. However, how dynamic filopodia translate external mechanical cues remains poorly understood. Recent studies show that the SARS-CoV-2 spike (S) protein binds the ACE2 receptor on airway multicilia and that cilia are required for viral infection(1) and sufficient to induce filopodial extension and viral binding. To test if spike protein is sufficient to induce filopodial expansion, we employed live-cell single-particle tracking with quantum dots targeting ACE2, to reveal a robust filopodia extension and virus binding mechanism requiring the enzymatic activity of ACE2. Using time-lapse imaging, we reveal that spike protein binding to filopodia is associated with intracellular actin remodeling, alterations in bulk cell stiffness, and an elevation in intracellular calcium levels linked to actin-rearrangement, filopodia initiation, and persistence. We propose the activation of ACE2 creates an active signaling and mechanosensory environment within adherent cells and airway epithelial cells that allows the remodeling of actin in filopodia to trap virus and potentially organize viral exit from cells.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.01.581813v1" target="_blank">Filopodial Mechanotransduction is regulated by Angiotensin-Converting Enzyme 2 (ACE2) and by SARS-CoV-2 spike protein</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Why is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study of the free enzyme and its complex with inhibitor 13b-K</strong> -
|
|||
|
|
<div>
|
|||
|
|
During the continuing evolution of SARS-CoV-2, the Omicron variant of concern emerged in the second half of 2021 and has been dominant since November that year. Along with its sublineages, it has maintained a prominent role ever since. The Nsp5 main protease (Mpro) of the Omicron virus is characterized by a single dominant mutation, P132H. Here we determined the X-ray crystal structures of the P132H mutant (or O-Mpro) as free enzyme and in complex with the Mpro inhibitor, the alpha-ketoamide 13b-K, and we conducted enzymology, biophysical as well as theoretical studies to characterize the O-Mpro. We found that O-Mpro has a similar overall structure and binding with 13b-K; however, it displays lower enzymatic activity and lower thermal stability compared to the WT-Mpro (with "WT" referring to the original Wuhan-1 strain). Intriguingly, the imidazole ring of His132 and the carboxylate plane of Glu240 are in a stacked configuration in the X-ray structures determined here. The empirical folding free energy calculations suggest that the O-Mpro dimer is destabilized relative to the WT-Mpro due to the less favorable van der Waals interactions and backbone conformation in the individual protomers. The all-atom continuous constant pH molecular dynamics (MD) simulations reveal that His132 and Glu240 display coupled titration. At pH 7, His132 is predominantly neutral and in a stacked configuration with respect to Glu240 which is charged. In order to examine whether the Omicron mutation eases the emergence of further Mpro mutations, we also determined crystal structures of the relatively frequent P132H+T169S double mutant but found little evidence for a correlation between the two sites.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.04.583178v1" target="_blank">Why is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study of the free enzyme and its complex with inhibitor 13b-K</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>A 10-valent composite mRNA vaccine against both influenza and COVID-19</strong> -
|
|||
|
|
<div>
|
|||
|
|
The COVID-19 pandemic caused by SARS-CoV-2 viruses has had a persistent and significant impact on global public health for four years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.05.583547v1" target="_blank">A 10-valent composite mRNA vaccine against both influenza and COVID-19</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>SARS-CoV-2 modulates NK cell responses via induction of HLA-E and triggers expansion of adaptive NK cells during acute infection</strong> -
|
|||
|
|
<div>
|
|||
|
|
HLA-E expression plays a central role for modulation of NK cell function by interaction with inhibitory NKG2A and stimulatory NKG2C receptors on canonical and adaptive NK cells, respectively. Here, we demonstrate that infection of human primary lung tissue with SARS-CoV-2 leads to increased HLA-E expression and show that processing of the peptide YLQPRTFLL from the spike protein is primarily responsible for the strong, dose-dependent increase of HLA-E. Targeting the peptide site within the spike protein revealed that a single point mutation was sufficient to abrogate the increase in HLA-E expression. Spike-mediated induction of HLA-E differentially affected NK cell function: whereas degranulation, IFN-gamma production, and target cell cytotoxicity were enhanced in NKG2C+ adaptive NK cells, effector functions were inhibited in NKG2A+ canonical NK cells. Analysis of a cohort of COVID-19 patients in the acute phase of infection revealed that adaptive NK cells were induced irrespective of the HCMV status, challenging the paradigm that adaptive NK cells are only generated during HCMV infection. During the first week of hospitalization, patients exhibited a selective increase of early NKG2C+CD57- adaptive NK cells whereas mature NKG2C+CD57+ cells remained unchanged. Further analysis of recovered patients suggested that the adaptive NK cell response is primarily driven by a wave of early adaptive NK cells during acute infection that wanes once the infection is cleared. Together, this study suggests that NK cell responses to SARS-CoV-2 infection are majorly influenced by the balance between canonical and adaptive NK cells via the HLA-E/NKG2A/C axis.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.04.583260v1" target="_blank">SARS-CoV-2 modulates NK cell responses via induction of HLA-E and triggers expansion of adaptive NK cells during acute infection</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Biological modifications of the immune response to COVID-19 vaccine in patients treated with anti-CD20 agents and immune-checkpoint inhibitors</strong> -
|
|||
|
|
<div>
|
|||
|
|
Investigating the impact of immune-modulating therapies on mRNA vaccine efficacy remains vital, transcending the immediate context of the COVID-19 pandemic. This study focuses on the differential immune responses to COVID-19 mRNA booster vaccines among healthy subjects, cancer patients undergoing treatment with immune-checkpoint inhibitors (ICIs), and those treated with B-cell depleting agents such as rituximab. Utilizing RNA sequencing, serology, and interferon gamma release assays, we charted the temporal dynamics of the immune response. Our findings indicate that ICIs maintain an immune profile similar to that of healthy individuals, whereas treatments like rituximab lead to a significant reduction in immune competence, affecting both humoral and cellular immunity. This research may not only help tailoring of vaccination strategies for those under immune-modulating treatments, but also deepens our understanding of the sophisticated interplay within the immune system in health and disease states, potentially informing therapeutic strategies across a spectrum of immunological conditions.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.05.583494v1" target="_blank">Biological modifications of the immune response to COVID-19 vaccine in patients treated with anti-CD20 agents and immune-checkpoint inhibitors</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Iterative In Silico Screening for Optimizing Stable Conformation of Anti-SARS-CoV-2 Nanobodies</strong> -
|
|||
|
|
<div>
|
|||
|
|
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 were measured through the NeighborSearch 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. To validate the efficacy ranking of the nanobodies we obtained, we calculated the binding affinities and dissociation constants (Kd) of all screened nanobodies using the PRODIGY web tool, and predicted the stability changes induced by all possible point mutations in nanobodies using the MAESTROWeb server. Furthermore, we examined the performance of the relationship between nanobodies’ ranking and their number of mutation-sensitive sites (Spearman correlation > 0.68), the results revealed a robust correlation, indicating that the superior nanobodies identified through our screening process exhibited fewer mutation hotspots and higher stability. This correlation analysis demonstrates the validity of our screening criteria, underscoring the suitability of these nanobodies for future development and practical implementation. In conclusion, this three-step 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.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.09.552633v2" target="_blank">Iterative In Silico Screening for Optimizing Stable Conformation of Anti-SARS-CoV-2 Nanobodies</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Prioritizing Lifestyle Factors for Effective Emotion Regulation: A Daily Study on First-Year College Students’ Well-Being During COVID-19</strong> -
|
|||
|
|
<div>
|
|||
|
|
The COVID-19 pandemic disrupted emerging adult first-year college students’ daily lives and well-being. Adaptive emotion regulation skills are crucial for this population that is in a transitioning phase of development during challenging times. This study assessed 1,796 ecological momentary assessments from 76 first-year college students’ daily usage of adaptive Dialectical Behavior Therapy (DBT) emotion regulation (ER) skills and momentary experiences of well-being during COVID-19 in the Spring of 2020. Participants were emerging adults aged 18 to 20 years, 71% female, and 46% white. Results from multilevel models revealed that specific ER skills consistently predict momentary well-being even when controlling for dispositional well-being. Moreover, on days of sufficient sleep reported, students reported higher well-being levels; on days with more interaction with others, students were more likely to engage in ER behaviors; and on weekends, students were less likely to engage in ER behaviors (but not avoid substances like alcohol).
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/7gxta/" target="_blank">Prioritizing Lifestyle Factors for Effective Emotion Regulation: A Daily Study on First-Year College Students’ Well-Being During COVID-19</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus</strong> -
|
|||
|
|
<div>
|
|||
|
|
Since the publication of the genome of SARS-CoV-2 - the causative agent of COVID-19 - in January 2020, many bioinformatic tools have been applied to annotate its proteins. Although efficient methods have been used, such as the identification of protein domains stored in Pfam, most of the proteins of this virus have no detectable homologous protein domains outside the viral taxa. As it is now well established that some viral proteins share similarities with proteins of their hosts, we decided to explore the hypothesis that this lack of homologies could be, at least in part, the result of the documented loss of sensitivity of Pfam Hidden Markov Models (HMMs) when searching for domains in “divergent organisms”. To improve the annotation of SARS-CoV-2 proteins, we used here the HHpred protein annotation tool and an available custom HH-suite database of HMMs specific to Homo sapiens proteins. To avoid “false positive predictions” as much as possible, we designed a robustness procedure to evaluate the HHpred results. In total, 6 robust similarities involving 6 distinct SARS-CoV-2 proteins were detected. Of these 6 similarities, 3 are already known and well documented, and one is in agreement with recent crystallographic results. We then examined carefully the two similarities that have not yet been reported in the literature. We first show that the C-terminal part of Spike S (the protein that binds the virion to the cell membrane by interacting with the host receptor, triggering infection) has similarities with the human prominin-1/CD133; after reviewing what is known about prominin-1/CD133, we suggest that the C-terminal part of Spike S could both improve the docking of Spike S to ACE2 (the main cell entry receptor for SARS-CoV-2) and be involved in the delivery of virions to regions where ACE2 is located in cells. Secondly, we show that the SARS-CoV-2 ORF3a protein shares similarities with human G protein-coupled receptors (GPCRs) belonging mainly to the “Rhodopsin family”. We conclude that the approach described here (or similar approaches) opens up new avenues of research to better understand SARS-CoV-2 and could be used to complement virus annotations, particularly for less-studied viruses.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.06.543855v2" target="_blank">Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Engineering customized viral receptors for various coronaviruses</strong> -
|
|||
|
|
<div>
|
|||
|
|
Coronaviruses display versatile receptor usage, yet in-depth characterization of coronaviruses lacking known receptor identities has been impeded by the absence of feasible infection models. Here, we developed an innovative strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building receptor frameworks comprising various function modules and generating specific epitope-targeting viral binding domains. We showed the key factors for CVRs to efficiently facilitate spike cleavage, membrane fusion, pseudovirus entry, and authentic virus amplification for various coronaviruses, resembling their native receptors. Applying this strategy, we delineated the accessible receptor binding epitopes for functional SARS-CoV-2 CVR design and elucidated the mechanism of entry supported by an amino-terminus domain (NTD) targeting S2L20-CVR. Furthermore, we created CVR-expressing cells for assessing antibodies and inhibitors against 12 representative coronaviruses from six subgenera, most of which lacking known receptors. Notably, a pan-sarbecovirus CVR supported entry of various sarbecoviruses, as well as amplification of a replicable HKU3 pseudovirus and the authentic strain RsHuB2019A. Through combining an HKU5-specific CVR with reverse genetics, we successfully rescued and cultured wild-type and fluorescence protein-incorporated HKU5, a receptor-unidentified merbecovirus. Our study demonstrated the great potential of CVR strategy in establishing native receptor-independent infection models, paving the way for studying various viruses that are challenging to culture due to the lack of susceptible cells.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.03.583237v1" target="_blank">Engineering customized viral receptors for various coronaviruses</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Heterogeneous hybrid immunity against Omicron variant JN.1 at 11 months following breakthrough infection</strong> -
|
|||
|
|
<div>
|
|||
|
|
A highly transmissible SARS-CoV-2 variant JN.1 is rapidly spreading throughout the nation, becoming the predominant strain in China and worldwide. However, the current immunity against the circulating JN.1 at population level has yet to be fully evaluated. We recruited representative cohorts with stratified age groups and diverse combinations of vaccination and/or infection in recent months, and promptly assessed humoral immunity for these subjects predominantly exhibiting hybrid immunity. We report that at 11 months following BA.5-wave breakthrough infection (BTI), these vaccinated individuals generally showed above-the-threshold yet low level of neutralizing activity against JN.1, with slightly greater potency observed in children and adolescents compared to adults and seniors. Meanwhile, XBB/EG.5-wave reinfection post-BTI significantly boosted the neutralizing antibodies against Omicron variants, including JN.1 in both adults (13.4- fold increase) and seniors (24.9-fold increase). To better understand respiratory mucosal protection against JN.1 over an extended period of months post-BTI, we profiled the humoral immunity in bronchoalveolar lavage samples obtained from vaccinated subjects with or without BTI, and revealed increased potency of neutralizing activity against the BA.5 and JN.1 variants in the respiratory mucosa through natural infection. Notably, at 11 months post-BTI, memory B cell responses against prototype and JN.1 were detectable in both blood and respiratory mucosa, displaying distinct memory features in the circulation and airway compartments. XBB/EG.5-wave reinfection drove the expansion of JN.1-specific B cells, along with the back-boosting of B cells responding to the ancestral viral strain, suggesting the involvement of immune imprinting. Together, this study indicates heterogeneous hybrid immunity over 11 months post-BTI, and underscores the vulnerability of individuals, particularly high-risk seniors, to JN.1 breakthrough infection. An additional booster with XBB-containing vaccine may greatly alleviate the onward transmission of immune-evasive SARS-CoV-2 variants.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.02.583082v1" target="_blank">Heterogeneous hybrid immunity against Omicron variant JN.1 at 11 months following breakthrough infection</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>B cell maturation restored ancestral germlines to control Omicron BA.2.86</strong> -
|
|||
|
|
<div>
|
|||
|
|
The unceasing interplay between SARS-CoV-2 and the human immune system has led to a continuous maturation of the virus and B cell response providing an opportunity to track their evolution in real time. We longitudinally analyzed the functional activity of almost 1,000 neutralizing human monoclonal antibodies (nAbs) isolated from vaccinated people, and from individuals with hybrid and super hybrid immunity (SH), developed after three mRNA vaccine doses and two breakthrough infections. The most potent neutralization and Fc functions against highly mutated variants, including BA.2.86, were found in the SH cohort. Despite different priming, epitope mapping revealed a convergent maturation of the functional antibody response. Neutralization was mainly driven by Class 1/2 nAbs while Fc functions were induced by Class 3/4 antibodies. Remarkably, broad neutralization was mediated by restored IGHV3-53/3-66 B cell germlines which, after heterogenous exposure to SARS-CoV-2 S proteins, increased their level of somatic hypermutations. Our study shows the resilience of the human immune system which restored previously expanded germlines and activated naive B cells to broaden the antibody repertoire of antibodies to control future SARS-CoV-2 variants.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.03.583187v1" target="_blank">B cell maturation restored ancestral germlines to control Omicron BA.2.86</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate AVX/COVID-12 Activates T Cells and Is Recognized by Antibodies from COVID-19 Patients and Vaccinated</strong> -
|
|||
|
|
<div>
|
|||
|
|
Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. This study analyses the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-{gamma}) in both CD4+ and CD8+ T-cells. In conclusion, the AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.01.582987v1" target="_blank">Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate AVX/COVID-12 Activates T Cells and Is Recognized by Antibodies from COVID-19 Patients and Vaccinated</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans</strong> -
|
|||
|
|
<div>
|
|||
|
|
Since the emergence of SARS-CoV-2 in Wuhan in 2019 its host reservoir has not been established. Phylogenetic analysis was performed on whole genome sequences (WGS) of 71 coronaviruses and a Breda virus. A subset comprising two SARS-CoV-2 Wuhan viruses and 8 of the most closely related coronavirus sequences were used for host reservoir analysis using Bayesian Evolutionary Analysis Sampling Trees (BEAST). Within these genomes, 20 core genome fragments were combined into 2 groups each with similar clock rates (5.9x10 -3 and 1.1x10 -3 subs/site/year). Pooling the results from these fragment groups yielded a most recent common ancestor (MRCA) shared between SARS-COV-2 and the bat isolate RaTG13 around 2007 (95% HPD: 2003, 2011). Further, the host of the MRCA was most likely a bat (probability 0.64 - 0.87). Hence, the spillover into humans must have occurred at some point between 2007 and 2019 and bats may have been the most likely host reservoir.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.25.568670v2" target="_blank">Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>The Effect of Analytical Thinking on Irrational Behaviors in Times of COVID-19: the Mediating Role of Misinformation Beliefs</strong> -
|
|||
|
|
<div>
|
|||
|
|
The present study was to investigate the influence of analytical thinking on irrational behaviors evoked by COVID-19 (including excessive epidemic prevention and hoarding behavior) and the mediating role of misinformation beliefs related to COVID-19 (including social and pseudoscientific beliefs) in a public health crisis. 1968 Chinese participants completed the Analytical Thinking Test, Misinformation Beliefs Questionnaire and Irrational Behavior Questionnaire online. The results showed that (1) Analytical thinking had a negative prediction on both excessive epidemic prevention and hoarding behavior; (2) misinformation beliefs, even social misinformation beliefs, partly mediated the relationship between the analytical thinking and irrational behaviors. These findings provide some useful references for effectively reducing people’s irrational behaviors during a public health crisis.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/tfjsv/" target="_blank">The Effect of Analytical Thinking on Irrational Behaviors in Times of COVID-19: the Mediating Role of Misinformation Beliefs</a>
|
|||
|
|
</div></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
|
|||
|
|
<ul>
|
|||
|
|
<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 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection <br/><b>Sponsors</b>: Novavax <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection.</strong> - <b>Conditions</b>: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection <br/><b>Interventions</b>: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo) <br/><b>Sponsors</b>: Sheng-Teng Huang <br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets <br/><b>Sponsors</b>: JKT Biopharma Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Safety & Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: IMNN-101 <br/><b>Sponsors</b>: Imunon <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<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 Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo <br/><b>Sponsors</b>: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of a Nasal Spray on Viral Respiratory Infections</strong> - <b>Conditions</b>: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold <br/><b>Interventions</b>: Device: Nasal Spray HSV Treatment <br/><b>Sponsors</b>: CEN Biotech; Urgo Research, Innovation & Development <br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: GS-441524; Drug: Placebo <br/><b>Sponsors</b>: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Active, not recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 <br/><b>Interventions</b>: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) <br/><b>Sponsors</b>: Selda Sarıkaya; Zonguldak Bulent Ecevit University <br/><b>Completed</b></p></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunomodulatory and anticytokine therapeutic potential of three Indian spices constituents and its hyaluronic acid conjugates for prevention and post COVID-19 complications: a computational modeling approach</strong> - Targeted drug delivery to SARS-CoV-2 host target proteins for preventing or blocking COVID-19 infection is making serious concern during COVID-19 pandemic and its consequent waves around the globe. People seek reliable, effective folkloric preventive medication for immediate and precautionary relief from COVID-19. These folkloric medicines were effective and saved many patients during the past COVID-19 pandemic. The current research study aims to deliver antiviral Indian spices phytocompounds…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Altered DNA methylation underlies monocyte dysregulation and immune exhaustion memory in sepsis</strong> - Monocytes can develop an exhausted memory state characterized by reduced differentiation, pathogenic inflammation, and immune suppression that drives immune dysregulation during sepsis. Chromatin alterations, notably via histone modifications, underlie innate immune memory, but the contribution of DNA methylation remains poorly understood. Using an ex vivo sepsis model, we show altered DNA methylation throughout the genome of exhausted monocytes, including genes implicated in immune…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting SIRT1 by Scopoletin to Inhibit XBB.1.5 COVID-19 Life Cycle</strong> - Natural products have historically driven pharmaceutical discovery, but their reliance has diminished with synthetic drugs. Approximately 35% of medicines originate from natural products. Scopoletin, a natural coumarin compound found in herbs, exhibits antioxidant, hepatoprotective, antiviral, and antimicrobial properties through diverse intracellular signaling mechanisms. Furthermore, it also enhances the activity of antioxidants. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What kind of a problem is loneliness? Representations of connectedness and participation from a study of telepresence technologies in the UK</strong> - Loneliness is represented in UK policy as a public health problem with consequences in terms of individual suffering, population burden and service use. However, loneliness is historically and culturally produced; manifestations of loneliness and social isolation also require social and cultural analysis. We explored meanings of loneliness and social isolation in the UK 2020-2022 and considered what the solutions of telepresence technologies reveal about the problems they are used to address….</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Integrated Metabolomic and transcriptomic analyses reveal deoxycholic acid promotes transmissible gastroenteritis virus infection by inhibiting phosphorylation of NF-kappaB and STAT3</strong> - CONCLUSIONS: We identified a significant metabolite, DCA, related to TGEV replication. It added TGEV replication in host cells by inhibiting phosphorylation of NF-κB and STAT3. This study provided novel insights into the metabolomic and transcriptomic alterations related to TGEV infection and revealed potential molecular and metabolic targets for the regulation of TGEV infection.</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Therapeutic role of miR-19a/b protection from influenza virus infection in patients with coronary heart disease</strong> - Patients with pre-existing medical conditions are at a heightened risk of contracting severe acute respiratory syndrome (SARS), SARS-CoV-2, and influenza viruses, which can result in more severe disease progression and increased mortality rates. Nevertheless, the molecular mechanism behind this phenomenon remained largely unidentified. Here, we found that microRNA-19a/b (miR-19a/b), which is a constituent of the miR-17-92 cluster, exhibits reduced expression levels in patients with coronary…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention</strong> - The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparative Immunogenicity and Neutralization Potency of Four Approved COVID-19 Vaccines in BALB/c Mice</strong> - CONCLUSION: Our results indicate significant immunogenicity and neutralization efficacy induced by PastoCovac Plus and Sinopharm, but not by Noora and SpikoGen. This suggests the need for additional comparative assessment of the potency and efficacy of these four vaccines in vaccinated subjects.</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potential Therapeutic Strategies and Drugs That Target Vascular Permeability in Severe Infectious Diseases</strong> - Severe infection pathogenicity is induced by processes such as pathogen exposure, immune cell activation, inflammatory cytokine production, and vascular hyperpermeability. Highly effective drugs, such as antipathogenic agents, steroids, and antibodies that suppress cytokine function, have been developed to treat the first three processes. However, these drugs cannot completely suppress severe infectious diseases, such as coronavirus disease 2019 (COVID-19). Therefore, developing novel drugs that…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Preliminary report on therapeutic potential of coal-derived carbon quantum dots against SARS-CoV-2 virus</strong> - Due to the pandemic of COVID-19 and subsequent emerging of new mutant strains, there has been a worldwide hunt for therapeutic and protective agents for its inhibition. In this short communication, for the first time, we report the coal-derived carbon quantum dot (CQD) for the possible therapeutic application against SARS-CoV-2. The synthesized C1-CQD is observed to be safe towards the normal cell line at highest dose, while effectively inhibiting growth of SARS-CoV2 (>95%) with IC(50) value of…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Membrane protein regulates the function of Spike by inhibiting its plasma membrane localization and enzymatic activity of Furin</strong> - The presence of a multibasic cleavage site in the Spike protein of SARS-CoV-2 makes it prone to be cleaved by Furin at the S1/S2 junction (aa. 685-686), which enhances the usage of TMPRSS2 to promote cell-cell fusion to form syncytia. Syncytia may contribute to pathology by facilitating viral dissemination, cytopathicity, immune evasion, and inflammation. However, the role of other SARS-CoV-2 encoding viral proteins in syncytia formation remains largely unknown. Here, we report that SARS-CoV-2 M…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Role of telerehabilitation in the rehabilitation of children with cerebral palsy during COVID-19: A review</strong> - Individuals with cerebral palsy (CP) have limited mobility and are unable to actively participate in tasks that are part of their daily living. Thus, continuous therapeutic sessions are required to keep such individuals active and engaged in the environment. Due to the coronavirus disease of 2019 (COVID-19) lockdowns, rehabilitation for children with CP was inhibited which consequently put them at risk of losing their functional gains which were obtained through previous in-person therapies. In…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prophylactic effect of ensitrelvir in mice infected with SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of coronavirus disease 2019 (COVID-19) and continues to be a major health concern worldwide. Strategies to protect individuals at high risk of COVID-19 are critical but are currently a largely unmet need. We evaluated the oral antiviral drug ensitrelvir, which specifically targets the SARS-CoV-2 3CL protease, for its efficacy as a pre-exposure prophylactic treatment. Aged BALB/c mice were subcutaneously treated…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Priming congruence and COVID-19 vaccination intention: a mediation analysis</strong> - CONCLUSIONS: Implications of these results are discussed in light of the socially situated cognition perspective and the congruence of (a) a societal context of communication toward the vaccine and the unvaccinated, (b) the participant’s degree of adherence to that communication, (c) the theme of priming, whether or not related to feeling connected to others. Implications of materialism priming are discussed, and the effect of commitment on intention to get vaccinated.</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A subunit-based influenza/SARS-CoV-2 Omicron combined vaccine induced potent protective immunity in BALB/c mice</strong> - Infection with influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant risk to human life, health, and the global economy. Vaccination is one of the most effective strategies in the fight against infectious viruses. In this study, we, for the first time, have evaluated the immunogenicity and protective effect of an influenza/SARS-CoV-2 Omicron subunit combined vaccine adjuvanted with MF59 and administered to BALB/c mice. Results showed that…</p></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
|
|||
|
|
|
|||
|
|
|
|||
|
|
<script>AOS.init();</script></body></html>
|