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<title>11 January, 2024</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>Variant-specific interactions at the plasma membrane: Heparan sulfate’s impact on SARS-CoV-2 binding kinetics</strong> -
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The worldwide spread of SARS-CoV-2 has been characterised by the emergence of several variants of concern (VOCs) presenting an increasing number of mutations in the viral genome. The spike glycoprotein, responsible for engaging the viral receptor ACE2, exhibits the highest density of mutations, suggesting an ongoing evolution to optimize viral entry. However, previous studies focussed on isolated molecular interactions, neglecting the intricate composition of the plasma membrane and the interplay between viral attachment factors. Our study explores the role of avidity and of the complexity of the plasma membrane composition in modulating the virus-host binding kinetics during the early stages of viral entry for the original Wuhan strain and three VOCs: Omicron BA.1, Delta, and Alpha. We employ fluorescent liposomes decorated with spike from several VOCs as virion mimics in single-particle tracking studies on native supported lipid bilayers derived from pulmonary Calu-3 cells. Our findings reveal an increase in the affinity of the multivalent bond to the cell surface for Omicron driven by an increased association rate. We show that heparan sulfate (HS), a sulfated glycosaminoglycan commonly expressed on cells’ plasma membrane, plays a central role in modulating the interaction with the cell surface and we observe a shift in its role from screening the interaction with ACE2 in early VOCs to an important binding factor for Omicron. This is caused by a ~10-fold increase in Omicron’s affinity to HS compared to the original Wuhan strain, as shown using atomic force microscopy-based single-molecule force spectroscopy. Our results show the importance of coreceptors, particularly HS, and membrane complexity in the modulation of the attachment in SARS-CoV-2 VOCs. We highlight a transition in the variants’ attachment strategy towards the use of HS as an initial docking site, which likely plays a role in shaping Omicron’s tropism towards infection of the upper airways, milder symptoms, and higher transmissibility.
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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/10.1101/2024.01.10.574981v1" target="_blank">Variant-specific interactions at the plasma membrane: Heparan sulfate’s impact on SARS-CoV-2 binding kinetics</a>
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</div></li>
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<li><strong>Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice</strong> -
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The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as Post-COVID syndrome (PCS). Current estimates suggest that more than 65 million people are grappling with PCS, encompassing several manifestations, including pulmonary, musculoskeletal, metabolic, and neuropsychiatric sequelae (cognitive and behavioral). The mechanisms underlying PCS remain unclear. The present study aimed to: (i) comprehensively characterize the acute effects of pulmonary inoculation of the betacoronavirus MHV-A59 in immunocompetent mice at clinical, cellular, and molecular levels; (ii) examine potential acute and long-term pulmonary, musculoskeletal, and neuropsychiatric sequelae induced by the betacoronavirus MHV-A59; and to (iii) assess sex-specific differences. Male and female C57Bl/6 mice were initially inoculated with varying viral titers (3x10^3 to 3x105 PFU/30 uL) of the betacoronavirus MHV-A59 via the intranasal route to define the highest inoculum capable of inducing disease without causing mortality. Further experiments were conducted with the 3x10^4 PFU inoculum. Mice exhibited an altered neutrophil/lymphocyte ratio in the blood in the 2nd and 5th day post-infection (dpi). Marked lung lesions were characterized by hyperplasia of the alveolar walls, infiltration of polymorphonuclear leukocytes (PMN) and mononuclear leukocytes, hemorrhage, increased concentrations of CCL2, CCL3, CCL5, and CXCL1 chemokines, as well as high viral titers until the 5th dpi. While these lung inflammatory signs resolved, other manifestations were observed up to the 60 dpi, including mild brain lesions with gliosis and hyperemic blood vessels, neuromuscular dysfunctions, anhedonic-like behavior, deficits in spatial working memory, and short-term aversive memory. These musculoskeletal and neuropsychiatric complications were exclusive to female mice and were prevented after ovariectomy. In summary, our study describes for the first time a novel sex-dependent model of PCS focused on neuropsychiatric and musculoskeletal disorders. This model provides a unique platform for future investigations regarding the effects of acute therapeutic interventions on the long-term sequelae unleashed by betacoronavirus infection.
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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/10.1101/2024.01.10.575003v1" target="_blank">Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice</a>
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</div></li>
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<li><strong>Effective assessment of CD4+ T cell Immunodominance patterns: impact of antigen processing and HLA restriction</strong> -
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<div>
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Identifying T cell epitopes is essential for studying and potentially tuning immune responses to pathogens. The polymorphic nature of major histocompatibility complex of class II (MHCII)-genes, and the complexity of the antigen processing mechanisms hinders the effective prediction of immunodominant patterns in humans, specially at the population level. Here, we combined the output of a reconstituted antigen processing system and of in silico prediction tools for SARS-CoV-2 antigens considering a broad-population coverage DRB1* panel to gain insights on immunodominance patterns. The two methods complement each other, and the resulting model improves upon single positive predictive values (PPV) from each of them to explain known epitopes. This model was used to design a minimalistic peptide pool (59 peptides) matching the performance reported for large overlapping peptide pools (> 500 peptides). Furthermore, almost 70 % of the candidates (23 peptides) selected for a frequent HLA background (DRB1<em>03:01/</em>07:01) feature immunodominant responses ex vivo, validating our platform for accessing T cell epitopes at the population level. The analysis of the impact of processing constraints reveals distinct impact of proteolysis and solvent accessible surface area on epitope selection depending on the antigen. Thus, considering these properties for antigens in question should improve available epitope prediction tools.
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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/10.1101/2024.01.10.574975v1" target="_blank">Effective assessment of CD4+ T cell Immunodominance patterns: impact of antigen processing and HLA restriction</a>
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</div></li>
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<li><strong>Inflammation-related pathology in the olfactory epithelium: its impact on the olfactory system in psychotic disorders</strong> -
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Smell deficits and neurobiological changes in the olfactory bulb (OB) and olfactory epithelium (OE) have been observed in schizophrenia and related disorders. The OE is the most peripheral olfactory system located outside the cranium, and is connected with the brain via direct neuronal projections to the OB. Nevertheless, it is unknown whether and how a disturbance of the OE affects the OB in schizophrenia and related disorders. Addressing this gap would be the first step in studying the impact of OE pathology in the disease pathophysiology in the brain. In this cross-species study, we observed that chronic, local OE inflammation with a set of upregulated genes in an inducible olfactory inflammation (IOI) mouse model led to a volume reduction, layer structure changes, and alterations of neuron functionality in the OB. Furthermore, IOI model also displayed behavioral deficits relevant to negative symptoms (avolition) in parallel to smell deficits. In first episode psychosis (FEP) patients, we observed a significant alteration in immune/inflammation-related molecular signatures in olfactory neuronal cells (ONCs) enriched from biopsied OE and a significant reduction in the OB volume, compared with those of healthy controls (HC). The increased expression of immune/inflammation-related molecules in ONCs was significantly correlated to the OB volume reduction in FEP patients, but no correlation was found in HCs. Moreover, the increased expression of human orthologues of the IOI genes in ONCs was significantly correlated with the OB volume reduction in FEP, but not in HCs. Together, our study implies a potential mechanism of the OE-OB pathology in patients with psychotic disorders (schizophrenia and related disorders). We hope that this mechanism may have a cross-disease implication, including COVID-19-elicited mental conditions that include smell deficits.
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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/10.1101/2022.09.23.509224v3" target="_blank">Inflammation-related pathology in the olfactory epithelium: its impact on the olfactory system in psychotic disorders</a>
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</div></li>
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<li><strong>Measuring concentration of nanoparticles in polydisperse mixtures using interferometric nanoparticle tracking analysis (iNTA)</strong> -
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<div>
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Quantitative measurements of nanoparticle concentration in liquid suspensions are in high demand, for example, in the medical and food industries. Conventional methods remain unsatisfactory, especially for polydisperse samples with overlapping size ranges. Recently, we introduced interferometric nanoparticle tracking analysis (iNTA) as a new method for high-precision measurement of nanoparticle size and refractive index. Here, we show that by counting the number of trajectories that cross the focal plane, iNTA can measure concentrations of subpopulations in a polydisperse mixture in a quantitative manner and without the need for a calibration sample. We evaluate our method on both monodisperse samples and mixtures of known concentrations. Furthermore, we assess the concentration of SARS-CoV-2 in supernatant samples obtained from infected cells.
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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/10.1101/2024.01.09.574819v1" target="_blank">Measuring concentration of nanoparticles in polydisperse mixtures using interferometric nanoparticle tracking analysis (iNTA)</a>
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</div></li>
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<li><strong>Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains</strong> -
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Since the start of the SARS-CoV-2 pandemic, the search for antiviral therapies has been at the forefront of medical research. To date, the 3CLpro inhibitor nirmatrelvir (Paxlovid) has shown the best results in clinical trials and the greatest robustness against variants. A second SARS-CoV-2 protease inhibitor, ensitrelvir (Xocova), has been developed. Ensitrelvir, currently in Phase 3, was approved in Japan under the emergency regulatory approval procedure in November 2022, and is available since March 31, 2023. One of the limitations for the use of antiviral monotherapies is the emergence of resistance mutations. Here, we experimentally generated mutants resistant to nirmatrelvir and ensitrelvir in vitro following repeating passages of SARS-CoV-2 in the presence of both antivirals. For both molecules, we demonstrated a loss of sensitivity for resistance mutants in vitro. Using a Syrian golden hamster infection model, we showed that the ensitrelvir M49L mutation, in the multi-passage strain, confers a high level of in vivo resistance. Finally, we identified a recent increase in the prevalence of M49L-carrying sequences, which appears to be associated with multiple repeated emergence events in Japan and may be related to the use of Xocova in the country since November 2022. These results highlight the strategic importance of genetic monitoring of circulating SARS-CoV-2 strains to ensure that treatments administered retain their full effectiveness.
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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/10.1101/2023.11.22.568013v2" target="_blank">Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains</a>
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<li><strong>How risky is it to not wear a mask? Moral emotions increase preventative health behaviours during the COVID-19 pandemic in India</strong> -
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Given the high transmission rates of the COVID-19 virus, policies aim at the maximal adoption of preventative health behaviours (PHBs) such as mask-wearing and maintaining physical distance. Moral emotions, risk perception, and message frames have previously been shown to foster favourable PHBs during various pandemics. To investigate the factors associated with PHBs during the COVID-19 pandemic, the present study explored the predictive role of moral emotions and message frames on PHBs (reduced physical contact and COVID-19 related policy support), controlling for risk perception regarding wearing a mask. Thus, a 2 (target of the message: self vs others) x 2 (valence: negative vs positive) between-groups experiment was conducted amongst Indians. Negative moral emotions predicted both (reduced) physical contact and policy support, and positive moral emotions predicted policy support. Exposure to differently framed health messages did not predict PHBs. The present study contributes to the field of health communication by highlighting the need for culture-specific practices such as focusing on the affective aspects of such communication. The results are increasingly relevant owing to the continuance of the COVID-19 crisis in India, and suggest that eliciting moral emotions throughCOVID-19 communication may significantly improve compliance with PHBs.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/vtxuk/" target="_blank">How risky is it to not wear a mask? Moral emotions increase preventative health behaviours during the COVID-19 pandemic in India</a>
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<li><strong>scRNA-seq reveals persistent aberrant differentiation of nasal epithelium driven by TNFα and TGFβ in post-COVID syndrome</strong> -
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<div>
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Post-COVID syndrome (PCS) currently affects approximately 3-17% of people following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has the potential to become a significant global health burden. PCS presents with various symptoms, and methods for improved PCS assessment are presently developed to guide therapy. Nevertheless, there are few mechanistic insights and treatment options. Here, we performed single-cell RNA transcriptomics on nasal biopsies from 33 patients suffering from PCS with mild, moderate, or severe symptoms. We identified 17 different cell clusters representing 12 unique cell populations, including all major epithelial cell types of the conducting airways and basal, secretory, and ciliated cells. Severe PCS was associated with decreased numbers of ciliated cells and the presence of immune cells. Ensuing inflammatory signaling upregulated TGF{beta} and induced an epithelial-mesenchymal transition, which led to the high abundance of basal cells and a mis-stratified epithelium. We confirmed the results in vitro using an air-liquid interface culture and validated TNF as the causal inflammatory cytokine. In summary, our results show that one mechanism for sustained PCS is not through continued viral load, but through the presence of immune cells in nasal tissue leading to impaired mucosal barrier function and repeated infections. These findings could be further explored as a therapeutic option akin to other chronic inflammatory diseases by inhibiting the TNF-TGF{beta} axis, restoring the nasal epithelium, and reducing respiratory tract-related infections.
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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/10.1101/2024.01.10.574801v1" target="_blank">scRNA-seq reveals persistent aberrant differentiation of nasal epithelium driven by TNFα and TGFβ in post-COVID syndrome</a>
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<li><strong>Efficient overexpression and purification of SARS-CoV-2 Nucleocapsid proteins in Escherichia coli</strong> -
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The fundamental biology of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (Ncap), its use in diagnostic assays and its potential application as a vaccine component have received considerable attention since the outbreak of the Covid19 pandemic in late 2019. Here we report the scalable expression and purification of soluble, immunologically active, SARS-CoV-2 Ncap in Escherichia coli. Codon-optimised synthetic genes encoding the original Ncap sequence and four common variants with an N-terminal 6His affinity tag (sequence MHHHHHHG) were cloned into an inducible expression vector carrying a regulated bacteriophage T5 synthetic promoter controlled by lac operator binding sites. The constructs were used to express Ncap proteins and protocols developed which allow efficient production of purified Ncap with yields of over 200 mg per litre of culture media. These proteins were deployed in ELISA assays to allow comparison of their responses to human sera. Our results suggest that there was no detectable difference between the 6His-tagged and untagged original Ncap proteins but there may be a slight loss of sensitivity of sera to other Ncap isolates.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.08.574531v1" target="_blank">Efficient overexpression and purification of SARS-CoV-2 Nucleocapsid proteins in Escherichia coli</a>
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<li><strong>Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19</strong> -
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SARS-CoV-2 can infect different organs, including the intestine. In Caco-2 intestinal cell line, SARS-CoV-2 modulates the ACE2 receptor expression and affects the expression of molecules involved in intercellular junctions. To further explore the possibility that the intestinal epithelium serves as an alternative infection route for SARS-CoV-2, we used a model of polarised intestinal cell monolayers grown on the polycarbonate membrane of Transwell inserts, inoculated with the virus either in the upper or lower chamber of culture. In both polarised Caco-2 cell monolayers and co-culture Caco-2/HT29 cell monolayer, apical SARS-CoV-2 inoculation was found to be much more effective in establishing infection than basolateral inoculation. In addition, apical SARS-CoV-2 infection triggers monolayer degeneration, as shown by histological examination, measurement of trans-epithelial electronic resistance, and cell adhesion molecule expression. During this process, the infectious viruses reach the lower chamber, suggesting either a transcytosis mechanism from the apical side to the basolateral side of cells, a paracellular trafficking of the virus after damage to intercellular junctions in the epithelial barrier, or both. Taken together, these data highlight a preferential tropism of SARS-CoV-2 for the apical side of the human intestinal tract and suggests that infection via the intestinal lumen leads to a systemic infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.08.574642v1" target="_blank">Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19</a>
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<li><strong>Lateral Flow Assays Biotesting by Utilizing Plasmonic Nanocrystals Made of Inexpensive Metals - Replacing Gold</strong> -
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Different kinds of nanoparticles can be conjugated with diverse biomolecular receptors and employed in biosensing to detect a target analyte (biomarkers of infections, cancer markers, etc.) from biological samples. This proven concept was largely used during the COVID-19 pandemic in over-the-counter gold nanoparticles-based paper strip tests. Considering that gold is expensive and is being largely depleted, here we show that novel and less expensive plasmonic counterparts, titanium nitride (TiN) nanoparticles, and copper nanoparticles covered with a gold shell (Cu@Au) perform comparable or better than gold nanoparticles. After functionalization, these novel nanoparticles provide a high signal, efficiency, and specificity when used on paper strip tests. This allows an easy visual determination of the positive signal and the development of more affordable paper-based test strips. Moreover, by conducting the machine learning study, we have shown that the bio-detection with TiN is more accurate than that with gold, demonstrating the advantage of a broadband plasmonic material. The implementation of lateral flow assays based on TiN and Cu@Au nanoparticles promises a drastic cost reduction of this technology and its widespread applications in tasks of biomedical diagnostics, environmental and food safety, security and doping screening.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.08.574723v1" target="_blank">Lateral Flow Assays Biotesting by Utilizing Plasmonic Nanocrystals Made of Inexpensive Metals - Replacing Gold</a>
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<li><strong>PathIntegrate: Multivariate modelling approaches for pathway-based multi-omics data integration</strong> -
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As terabytes of multi-omics data are being generated, there is an ever-increasing need for methods facilitating the integration and interpretation of such data. Current multi-omics integration methods typically output lists, clusters, or subnetworks of molecules related to an outcome. Even with expert domain knowledge, discerning the biological processes involved is a time-consuming activity. Here we propose PathIntegrate, a method for integrating multi-omics datasets based on pathways, designed to exploit knowledge of biological systems and thus provide interpretable models for such studies. PathIntegrate employs single-sample pathway analysis to transform multi-omics datasets from the molecular to the pathway-level, and applies a predictive single-view or multi-view model to integrate the data. Model outputs include multi-omics pathways ranked by their contribution to the outcome prediction, the contribution of each omics layer, and the importance of each molecule in a pathway. Using semi-synthetic data we demonstrate the benefit of grouping molecules into pathways to detect signals in low signal-to-noise scenarios, as well as the ability of PathIntegrate to precisely identify important pathways at low effect sizes. Finally, using COPD and COVID-19 data we showcase how PathIntegrate enables convenient integration and interpretation of complex high-dimensional multi-omics datasets. The PathIntegrate Python package is available at https://github.com/cwieder/PathIntegrate.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.09.574780v1" target="_blank">PathIntegrate: Multivariate modelling approaches for pathway-based multi-omics data integration</a>
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<li><strong>Durability of protection from original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes among adults in the United States — September 2022–August 2023</strong> -
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Objective: To evaluate the durability of protection provided by original monovalent and bivalent COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes Design: Multicenter case-control design with prospective enrollment Setting: 26 hospitals in 20 US states Participants: Adults aged ≥18 years admitted to hospital with COVID-19-like illness from 8 September 2022 to 31 August 2023 Main outcome measures: The main outcomes were absolute and relative vaccine effectiveness of original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes, including advanced respiratory support (defined as receipt of high-flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation [IMV]) and IMV or death. Vaccine effectiveness was estimated using multivariable logistic regression, in which the odds of vaccination (versus being unvaccinated or receiving original monovalent vaccination only) were compared between COVID-19 case patients and control-patients. Bivalent vaccine effectiveness analyses were stratified by time since dose receipt. Results: Among 7028 adults without immunocompromising conditions, 2924 (41.6%) were COVID-19 case patients and 4104 (58.4%) were control patients. Compared to unvaccinated patients, absolute vaccine effectiveness against COVID-19-associated hospitalization was 6% (-7% to 17%) for original monovalent doses only (median time since last dose [IQR] = 421 days [304-571]), 52% (39% to 61%) for a bivalent dose received 7-89 days earlier, and 13% (-10% to 31%) for a bivalent dose received 90-179 days earlier. Absolute vaccine effectiveness against COVID-19-associated advanced respiratory support was 31% (15% to 45%) for original monovalent doses only, 66% (47% to 78%) for a bivalent dose received 7-89 days earlier, and 33% (-1% to 55%) for a bivalent dose received 90-179 days earlier. Absolute vaccine effectiveness against COVID-19-associated IMV or death was 51% (34% to 63%) for original monovalent doses only, 61% (35% to 77%) for a bivalent dose received 7-89 days earlier, and 50% (11% to 71%) for a bivalent dose received 90-179 days earlier. Conclusion: When compared to original monovalent vaccination only, bivalent COVID-19 vaccination provided additional protection against COVID-19-associated hospitalization and certain severe in-hospital outcomes within 3 months of dose receipt. By 3-6 months, protection from a bivalent dose declined to a level similar to that remaining from original monovalent vaccination only. Although no protection remained from original monovalent vaccination against COVID-19-associated hospitalization, it provided durable protection against severe in-hospital outcomes >1 year after receipt of the last dose, particularly against IMV or death.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.07.24300910v1" target="_blank">Durability of protection from original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes among adults in the United States — September 2022–August 2023</a>
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<li><strong>How executive control and emotional reactivity influence coping strategies in psychiatric patients during the COVID-19 pandemic</strong> -
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Background: During times of environmental challenges, adaptive coping strategies are essential to maintain mental health. Coping relies on executive control, which is often impaired in individuals with psychiatric disorders. Furthermore, emotional reactivity may interfere with executive control. Studying the association between cognitive skills and adaptive coping strategies, as well as the potential impact of emotional reactivity, could inform how we can provide mental support during large-scale adversity. In this study we examined coping strategies in a thoroughly phenotyped psychiatric cohort, the MIND-Set cohort, during the early COVID-19 pandemic stage. Methods: We studied 1) the association between coping and both subjective and objective executive control before the pandemic, and three different coping strategies used during the pandemic, 2) the mediating role of emotional reactivity, indexed by amygdala reactivity, and 3) the moderating role of the presence of a psychiatric diagnosis in these associations. After finding no specific impact of patient or control status in this association, we decided to post-hoc study the transdiagnostic impact of depression severity in these associations. Results: showed 1) only a significant association between subjective executive control and a self-reported positive reappraisal style and corona-related reappraisal. However, after controlling for depression severity, this association was no longer significant. Additionally, objective executive control was only directly associated with right amygdala reactivity, while amygdala reactivity in neither of the hemispheres mediated the association between executive control and any of the coping styles. Furthermore, the type of diagnosis did not moderate the association between executive control and coping. Conclusion: Our findings firstly underline the difference between self-reported and performance based executive control. While both deficits in subjective and performance based EC may play a role in the persistence of psychiatric symptomatology, this finding emphasizes how depressive symptoms or negative affect can impact reappraisal ability. As this ability is fundamental to staying resilient, treatments focused on reducing negative affect and thereby training reappraisal are pivotal in the maintenance of mental health in the entire population during environmental challenges.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.08.24300980v1" target="_blank">How executive control and emotional reactivity influence coping strategies in psychiatric patients during the COVID-19 pandemic</a>
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<li><strong>Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants</strong> -
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The spike glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to accumulate substitutions, leading to breakthrough infections of vaccinated individuals and prompting the development of updated booster vaccines. Here, we determined the specificity and functionality of antibody and B cell responses following exposure to BA.5 and XBB variants in individuals who received ancestral SARS-CoV-2 mRNA vaccines. BA.5 exposures elicited antibody responses that primarily targeted epitopes conserved between the BA.5 and ancestral spike, with poor reactivity to the XBB.1.5 variant. XBB exposures also elicited antibody responses that targeted epitopes conserved between the XBB.1.5 and ancestral spike. However, unlike BA.5, a single XBB exposure elicited low levels of XBB.1.5-specific antibodies and B cells in some individuals. Pre-existing cross-reactive B cells and antibodies were correlated with stronger overall responses to XBB but weaker XBB-specific responses, suggesting that baseline immunity influences the activation of variant-specific SARS-CoV-2 responses.
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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/10.1101/2024.01.08.24301002v1" target="_blank">Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase III Clinical Study Evaluating the Efficacy and Safety of WPV01 in Patients With Mild/Moderate COVID-19</strong> - <b>Conditions</b>: Mild to Moderate COVID-19 <br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo <br/><b>Sponsors</b>: Westlake Pharmaceuticals (Hangzhou) Co., Ltd. <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Integrated Mindfulness-based Health Qigong Intervention for COVID-19 Survivors and Caregivers</strong> - <b>Conditions</b>: COVID-19 Infection <br/><b>Interventions</b>: Other: Mindfulness-based Health Qigong Intervention <br/><b>Sponsors</b>: The Hong Kong Polytechnic University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 and Influenza A/B in Point-of-Care and Non-Laboratory Settings</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Aptitude Medical Systems Metrix COVID/Flu Test <br/><b>Sponsors</b>: Aptitude Medical Systems; Biomedical Advanced Research and Development Authority <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can Doctors Reduce COVID-19 Misinformation and Increase Vaccine Uptake in Ghana? A Cluster-randomised Controlled Trial</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Motivational Interviewing, AIMS; Behavioral: Facility engagement <br/><b>Sponsors</b>: London School of Economics and Political Science; Innovations for Poverty Action; Ghana Health Services <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 Aerobic Exercises Versus Incentive Spirometer Device on Post-covid Pulmonary Fibrosis Patients</strong> - <b>Conditions</b>: Lung Fibrosis Interstitial; Post-COVID-19 Syndrome <br/><b>Interventions</b>: Other: Aerobic Exercises; Device: Incentive Spirometer Device; Other: Traditional Chest Physiotherapy <br/><b>Sponsors</b>: McCarious Nahad Aziz Abdelshaheed Stephens; Cairo University <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>Long COVID Ultrasound Trial</strong> - <b>Conditions</b>: Long Covid <br/><b>Interventions</b>: Device: Splenic Ultrasound <br/><b>Sponsors</b>: SecondWave Systems Inc.; University of Minnesota; MCDC (United States Department of Defense) <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity After COVID-19 Vaccines in Adapted Schedules</strong> - <b>Conditions</b>: Coronavirus Disease 2019; COVID-19 <br/><b>Interventions</b>: Drug: BNT162b2 30µg; Drug: BNT162b2 20µg; Drug: BNT162b2 6µg; Drug: mRNA-1273 100µg; Drug: mRNA-1273 50µg; Drug: ChAdOx1-S [Recombinant] <br/><b>Sponsors</b>: Universiteit Antwerpen <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>Could Wearing Face Mask Have Affected Demodex Parasite</strong> - <b>Conditions</b>: Pandemic, COVID-19; Demodex Infestation <br/><b>Interventions</b>: Diagnostic Test: standard superficial skin biopsy (SSSB) <br/><b>Sponsors</b>: Nurhan Döner Aktaş <br/><b>Completed</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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural flavonoid pectolinarin computationally targeted as a promising drug candidate against SARS-CoV-2</strong> - Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular…</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>Structure-based Virtual Screening from Natural Products as Inhibitors of SARS-CoV-2 Spike Protein and ACE2-h Receptor Binding and their Biological Evaluation In vitro</strong> - CONCLUSION: Compound B-8 can be used as a scaffold to develop new and more efficient antiviral drugs.</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>Lipid Metabolism Modulation during SARS-CoV-2 Infection: A Spotlight on Extracellular Vesicles and Therapeutic Prospects</strong> - Extracellular vesicles (EVs) have a significant impact on the pathophysiological processes associated with various diseases such as tumors, inflammation, and infection. They exhibit molecular, biochemical, and entry control characteristics similar to viral infections. Viruses, on the other hand, depend on host metabolic machineries to fulfill their biosynthetic requirements. Due to potential advantages such as biocompatibility, biodegradation, and efficient immune activation, EVs have emerged 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><em>FHL2</em> Inhibits SARS-CoV-2 Replication by Enhancing <em>IFN-β</em> Expression through Regulating <em>IRF-3</em></strong> - SARS-CoV-2 triggered the global COVID-19 pandemic, posing a severe threat to public health worldwide. The innate immune response in cells infected by SARS-CoV-2 is primarily orchestrated by type I interferon (IFN), with IFN-β exhibiting a notable inhibitory impact on SARS-CoV-2 replication. FHL2, acting as a docking site, facilitates the assembly of multiprotein complexes and regulates the transcription of diverse genes. However, the association between SARS-CoV-2 and FHL2 remains unclear. In…</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>Comparative Analysis of Cyclization Techniques in Stapled Peptides: Structural Insights into Protein-Protein Interactions in a SARS-CoV-2 Spike RBD/hACE2 Model System</strong> - Medicinal chemistry is constantly searching for new approaches to develop more effective and targeted therapeutic molecules. The design of peptidomimetics is a promising emerging strategy that is aimed at developing peptides that mimic or modulate the biological activity of proteins. Among these, stapled peptides stand out for their unique ability to stabilize highly frequent helical motifs, but they have failed to be systematically reported. Here, we exploit chemically diverse helix-inducing i,…</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>Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs</strong> - Human society is facing the threat of various viruses. Proteases are promising targets for the treatment of viral infections. In this study, we collected and profiled 170 protease sequences from 125 viruses that infect humans. Approximately 73 of them are viral 3-chymotrypsin-like proteases (3CL^(pro)), and 11 are pepsin-like aspartic proteases (PAPs). Their sequences, structures, and substrate characteristics were carefully analyzed to identify their conserved nature for proposing a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Viral Targeting of Importin Alpha-Mediated Nuclear Import to Block Innate Immunity</strong> - Cellular nucleocytoplasmic trafficking is mediated by the importin family of nuclear transport proteins. The well-characterized importin alpha (IMPA) and importin beta (IMPB) nuclear import pathway plays a crucial role in the innate immune response to viral infection by mediating the nuclear import of transcription factors such as IRF3, NFκB, and STAT1. The nuclear transport of these transcription factors ultimately leads to the upregulation of a wide range of antiviral genes, including IFN 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>5’-cap RNA/SAM mimetic conjugates as bisubstrate inhibitors of viral RNA cap 2’-O-methyltransferases</strong> - Viral RNA cap 2’-O-methyltransferases are considered promising therapeutic targets for antiviral treatments, as they play a key role in the formation of viral RNA cap-1 structures to escape the host immune system. A better understanding of how they interact with their natural substrates (RNA and the methyl donor SAM) would enable the rational development of potent inhibitors. However, as few structures of 2’-O-MTases in complex with RNA have been described, little is known about substrate…</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>Correction to: Dihydroisocoumarins of Hydrangea macrophylla var. thunbergii inhibit binding of the SARS-CoV-2 spike protein to ACE2</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>Gut microbiota-derived butyrate promotes coronavirus TGEV infection through impairing RIG-I-triggered local type I interferon responses via class I HDAC inhibition</strong> - Swine enteric coronaviruses (SECoVs) infection in vivo alters the composition of short-chain fatty acids (SCFAs)-producing gut microbiota, but whether microbiota-derived SCFAs impact coronavirus gastrointestinal infection is largely unknown. Here, we demonstrated that SCFAs, particularly butyrate, substantially increased alphacoronavirus TGEV infection at the late stage of infection, without affecting viral attachment or internalization. Furthermore, enhancement of TGEV by butyrate depended on…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An investigation into the usage of black cumin derivatives against cancer and COVID-19 as the nature medicine</strong> - Black cumin has been used as a spice and food preservative for years. Thymol, thymoquinone, thymohydroquinone and dihydrothymoquinone are the most important natural agents in black cumin. In order to determine the most active compound in black cumin the theoretical calculations have been carried out in different phases by using the density functional theory (DFT). The inhibition effect of black cumin derivatives on Histone deacetylase 2 (HDAC2) has been determined and supported the experimental…</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>Multiple redox switches of the SARS-CoV-2 main protease in vitro provide opportunities for drug design</strong> - Besides vaccines, the development of antiviral drugs targeting SARS-CoV-2 is critical for preventing future COVID outbreaks. The SARS-CoV-2 main protease (M^(pro)), a cysteine protease with essential functions in viral replication, has been validated as an effective drug target. Here, we show that M^(pro) is subject to redox regulation in vitro and reversibly switches between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues….</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>Antibacterial and Antiviral Activities of Silver Nanocluster/Silica Composite Coatings Deposited onto Air Filters</strong> - The indoor air quality should be better controlled and improved to avoid numerous health issues. Even if different devices are developed for air filtration, the proliferation of microorganisms under certain conditions must be controlled. For this purpose, a silver nanocluster/silica composite coating was deposited via a cosputtering technique onto fiber glass and polymeric based substrates. The aim of this work is focused on the evaluation of the antibacterial and antiviral effects of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2<sup>+</sup> Cells</strong> - The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2^(+) lung cells during a viral infection cycle should prevent viral S protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, we construct dual-drug-combined…</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 silico</em> Evaluation of ACE2 Inhibition by <em>Prunus armeniaca</em> L. and <em>in vivo</em> Toxicity Study</strong> - CONCLUSION: Four compounds from Prunus armeniaca seem to exert an inhibitory potential of ACE2.</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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