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170 lines
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<title>13 December, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>Leveraging Tuberculosis Programs for Future Pandemic Preparedness: A Retrospective Look on COVID-19</strong> -
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<div>
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Worldwide, COVID-19 has decimated healthcare systems and highlighted the pressing need to ensure resilience for future pandemics. Given the almost 30% likelihood of another respiratory disease similar to COVID-19 manifesting in the next 10 years, it is imperative to prioritize pandemic preparedness in the immediate future. To this end, tuberculosis (TB) and its management share many similarities to respiratory disease protection, offering an opportunity to dually strengthen TB programs and protect against future pandemics. Looking at data from the World Health Organization (WHO), Global Fund, Our World in Data, and domestic health ministries. It was hypothesized that countries that had better TB program strength going into the pandemic fared better with COVID-19 than those with poorer TB treatment. It was found that countries that recovered their TB program strength (as measured by TB treatment coverage percentages) to or above pre-pandemic levels fared better in terms of COVID-19 pandemic incidence and death. Case studies helped identify common factors across resilient TB platforms in dually successful COVID-19 and TB countries, including community trust, co-epidemic responses that were able to maintain continuity of care, sustained innovation, comprehensive communication across public and private sectors, and maintenance of donor support for TB programs through the pandemic.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/t23ed/" target="_blank">Leveraging Tuberculosis Programs for Future Pandemic Preparedness: A Retrospective Look on COVID-19</a>
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</div></li>
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<li><strong>EduMap: Navigating a Learning Adventure</strong> -
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<div>
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Directed study maps are often used in order to create an overlay of knowledge relations. However, these connections often have to manually be created by subject matter and IT experts, which, although are a ground truth, limit these user to the topics of the maps at hand. To address this, we propose EduMap, which takes advantage of GPT 3.5 in a few-shot setting to create a study map for any user-provided topic. We conducted two user studies to address various aspects of the map: (1) A quantitative study to test out the effectiveness of this map medium in the context of navigating information concerning COVID-19 in a expert-curated graph, and (2) A quantitative study to test out the accuracy and usefulness of GPT-generated graphs. Our results show that the map medium is effective, and, though the graphs produced make sense, there is work to be done before it can be considered ground truth, with issues of vague topics and improper connections between topics arising. Altogether, our results establish a baseline for AI-generated study maps to be improved upon in the future with ground truth to create a more trustworthy software.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/edarxiv/ez2bk/" target="_blank">EduMap: Navigating a Learning Adventure</a>
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</div></li>
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<li><strong>SARS-CoV-2 induces acute neurological signs while Calcitonin Gene-Related Peptide (CGRP) signaling blockade reduces interleukin 6 (IL-6) release and weight loss in mouse models</strong> -
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<div>
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COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.23.563669v4" target="_blank">SARS-CoV-2 induces acute neurological signs while Calcitonin Gene-Related Peptide (CGRP) signaling blockade reduces interleukin 6 (IL-6) release and weight loss in mouse models</a>
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</div></li>
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<li><strong>SARS-CoV-2 nsp15 preferentially degrades AU-rich dsRNA via its dsRNA nickase activity</strong> -
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<div>
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It has been proposed that coronavirus nsp15 mediates evasion of host cell double-stranded (ds) RNA sensors via its uracil-specific endoribonuclease activity. However, how nsp15 processes viral dsRNA, commonly considered as a genome replication intermediate, remains elusive. Previous research has mainly focused on short single-stranded RNA as substrates, and whether nsp15 prefers single-stranded or double-stranded RNA for cleavage is controversial. In the present work, we prepared numerous RNA substrates, including both long substrates mimicking the viral genome and short defined RNA, to clarify the substrate preference and cleavage pattern of SARS-CoV-2 nsp15. We demonstrated that SARS-CoV-2 nsp15 preferentially cleaved flexible pyrimidine nucleotides located in AU-rich areas and mismatch-containing areas in dsRNA via a nicking manner. The AU content and distribution in dsRNA along with the RNA length affected cleavage by SARS-CoV-2 nsp15. Because coronavirus genomes generally have a high AU content, our work supported the mechanism that coronaviruses evade the antiviral response mediated by host cell dsRNA sensors by using nsp15 dsRNA nickase to directly cleave dsRNA intermediates formed during genome replication and transcription.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.11.571056v1" target="_blank">SARS-CoV-2 nsp15 preferentially degrades AU-rich dsRNA via its dsRNA nickase activity</a>
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</div></li>
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<li><strong>G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2</strong> -
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<div>
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The glucose-6-phosphate dehydrogenase (G6PD) deficiency is X-linked and is the most common enzymatic deficiency disorder globally. It is a crucial enzyme for the pentose phosphate pathway and produces NADPH, which plays a vital role in the regulation of oxidative stress of many cell types. The deficiency of G6PD causes hemolytic anemia, diabetes, cardiovascular and neurological disorders. Notably, the patient with G6PD deficiency was severely affected by SARS-CoV-2 and showed prolonged COVID-19 symptoms, neurological impacts, and high mortality. However, the mechanism of COVID-19 severity in G6PD deficient patients is still ambiguous. Here, using a CRISPR-edited G6PD deficient human microglia cell culture model, we observed a significant reduction in NADPH and an increase in basal reactive oxygen species (ROS) in microglia. Interestingly, the deficiency of the G6PD-NAPDH axis impairs induced nitric oxide synthase (iNOS) mediated nitric oxide (NO) production which plays a fundamental role in inhibiting viral replication. Surprisingly, we also observed that the deficiency of the G6PD-NADPH axis reduced lysosomal acidification, which further abrogates the lysosomal clearance of viral particles. Thus, impairment of NO production and lysosomal acidification as well as redox dysregulation in G6PD deficient microglia altered innate immune response, promoting the severity of SARS-CoV-2 pathogenesis.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.570971v1" target="_blank">G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2</a>
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</div></li>
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<li><strong>The complement pattern recognition molecule CL-11 promotes invasion and injury of respiratory epithelial cells by SARS-CoV-2.</strong> -
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<div>
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Collectin-11 is a soluble C-type lectin produced at epithelial surfaces to initiate pathogen elimination by complement. Given the respiratory epithelium is a source of CL-11 and downstream complement-pathway components, we investigated the potential of CL-11 to impact the pathogenicity of SARS-CoV-2. While the SARS-CoV-2 spike trimer could bind CL-11 and trigger complement activation followed by MAC formation, the virus was resistant to lysis. Surprisingly, virus production by infected respiratory epithelial cells was enhanced by CL-11 opsonisation of virus but this effect was fully inhibited by sugar-blockade of CL-11. Moreover, SARS-CoV-2 spike protein expressed at the bronchial epithelial cell surface was associated with increased CL-11 binding and MAC formation. We propose that SARS-CoV-2 pathogenicity is exacerbated both by resistance to complement and CL-11 driven respiratory cell invasion and injury at the portal of entry. Contrary to expectation, CL-11 blockade could offer a novel approach to limit the pathogenicity of SARS-CoV-2.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.11.571109v1" target="_blank">The complement pattern recognition molecule CL-11 promotes invasion and injury of respiratory epithelial cells by SARS-CoV-2.</a>
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</div></li>
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<li><strong>Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures</strong> -
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<div>
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Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a ‘preeclampsia-like syndrome’. However, the mechanisms underpinning SARS-CoV-2-induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS-CoV-2 infection. Methods: We utilized whole-transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS-CoV-2 in the third trimester of their pregnancy (n=7) and those collected prior to the start of the coronavirus disease 2019 (COVID-19) pandemic (n=9). Results: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified signatures associated with hypoxia and placental dysfunction during SARS-CoV-2 infection in pregnancy. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH), and preeclampsia (FLT1, EGFR, KISS1, PAPPA2), were enriched with SARS-CoV-2. Pathways related to increased nutrient uptake, vascular tension, hypertension, and inflammation, were also enriched in SARS-CoV-2 samples compared to uninfected controls. Conclusions: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS-CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.20.524893v2" target="_blank">Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures</a>
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</div></li>
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<li><strong>Birdwatchers’ resilience to perturbation in India buffers citizen science from pandemic-induced biases</strong> -
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<div>
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Most systematic projects to monitor bird populations, like breeding bird surveys, require large and coordinated volunteer networks that are lacking in many parts of the world such as the Global South. Data from less systematic citizen science (CS) programmes offer an alternative to data from systematic initiatives in these regions, but the semi-structured nature of such data also presents several challenges. The utility of semi-structured CS data to monitor bird species abundance is contingent on how, where, and how comparably birdwatchers watch birds, year on year. Trends inferred directly from the data can be confounded during years when birdwatchers may behave differently, such as during the COVID-19 pandemic. We wanted to ascertain how the data uploaded from India to one such CS platform, eBird, was impacted by this deadliest global pandemic of the 21st century. To understand whether eBird data from the pandemic years in India is useful and comparable to data from adjacent years, we explored several quantitative and qualitative aspects of the data (such as birdwatcher behaviour) at multiple spatial and temporal scales. We found no negative impact of the pandemic on data generation. Data characteristics changed largely only during the peak pandemic months characterised by high fatality rates and strict lockdowns, possibly due to decreased human mobility and social interaction. It remained similar to the adjacent years during the rest of this restrictive period, thereby reducing the impact of the aberrant peak months on any annual inference. Moreover, impacts on data characteristics varied widely across states in India, resulting in no strong consistent trend at the national level–unlike results from elsewhere in the world. Our findings show that birdwatchers in India as contributors to CS were resilient to disturbance, and that the effects of the pandemic on birdwatching effort and birdwatcher behaviour are highly scale- and context-dependent. In summary, eBird data in India from the pandemic years remains useful and interpretable for most large-scale applications, such as abundance trend estimation, but will benefit from preliminary data quality checks when utilised at a fine scale.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.11.571083v1" target="_blank">Birdwatchers’ resilience to perturbation in India buffers citizen science from pandemic-induced biases</a>
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</div></li>
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<li><strong>A Pan-respiratory Antiviral Chemotype Targeting a Host Multiprotein Complex</strong> -
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<div>
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We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease.
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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/10.1101/2021.01.17.426875v4" target="_blank">A Pan-respiratory Antiviral Chemotype Targeting a Host Multiprotein Complex</a>
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</div></li>
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<li><strong>Cold Atmospheric Helium Plasma In The Post-Covid Era: A Promising Tool For The Disinfection Of Silicone Endotracheal Prostheses</strong> -
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<div>
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The COVID-19 pandemic resulted in a high prevalence of laryngotracheal stenosis. The endoluminal tracheal prostheses used to treat this condition are made of medical-grade silicone (MGS). Despite their excellent properties, the main limitation of these prostheses is the formation of a polymicrobial biofilm on their surfaces that interacts with the underlying mucosa, causing local inflammation and interfering with the local healing process, ultimately leading to further complications in the clinical scenario. Cold atmospheric plasma (CAP) shows antibiofilm properties on several microbial species. The present study evaluated the inhibitory effect of CAP on multispecies biofilms grown on MGS surfaces. In addition to the MGS characterization before and after CAP exposure, the cytotoxicity of CAP on immortalized human bronchial epithelium cell line (BEAS-2B) was evaluated. The aging time test reported that CAP could temporarily change the MGS surface wetting characteristics from hydrophilic (80.5 degrees) to highly hydrophilic (< 5 degrees). ATR-FTIR shows no significant alterations in the surficial chemical composition of MGS before and after CAP exposure for 5 min. A significant log reduction of viable cells in mono-species biofilms (log CFU/mL) of C. albicans, S. aureus, and P. aeruginosa (0.636, 0.738, and 1.445, respectively) were detected after CAP exposure. Multi-species biofilms exposed to CAP showed significant viability reduction for C. albicans and S. aureus (1.385 and 0.831, respectively). The protocol was not cytotoxic to BEAS-2B. It could be concluded that CAP can be a simple and effective method to delay the multi-species biofilm formation inside the endotracheal prosthesis.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.10.570744v1" target="_blank">Cold Atmospheric Helium Plasma In The Post-Covid Era: A Promising Tool For The Disinfection Of Silicone Endotracheal Prostheses</a>
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</div></li>
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<li><strong>CITY LEADERSHIP IN PARA-DIPLOMACY: DRIVERS OF JAKARTA’S INTERNATIONAL ENGAGEMENT IN ADDRESSING COVID-19 PANDEMIC</strong> -
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<div>
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The outbreak of the COVID-19 pandemic has impacted all the world’s aspects, including the interactions among governments. While some either chose to conflict with others or overlooked the pandemic, the rest attempted to collaborate in addressing the new global threat. Mega-cities in many countries were the most suffering regions due to the enormous virus-confirmed cases, deaths, and economic declines, intertwining with other urban issues. As the largest city in Southeast Asia and Indonesia, Jakarta also experienced an unprecedented crisis. However, apart from the efforts to tackle the crisis at home, the city showed its international engagement in addressing the issue together with other world cities as its para-diplomacy. This research aimed to answer the driving factors encouraging the city for such engagement. This research employed the qualitative method with descriptive analysis and the city leadership theory proposed by Rapoport, Acuto, and Grcheva. This research found that Jakarta’s international engagement in addressing the pandemic as the city leadership action was driven by the role of city leader, decentralization and global city networking, and the regional COVID-19 policies and internet representing three elements in the theory: actor, structures, and tools. This paper argues that cities within the global city networking have demonstrated their stronger role during the pandemic, providing opportunities for nation branding by regional initiatives in handling the pandemic in addition to state foreign policy. As cities have been more consolidated within the networks, seeing the city leadership in responding to global issues merits attention among scholars.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/6f3j5/" target="_blank">CITY LEADERSHIP IN PARA-DIPLOMACY: DRIVERS OF JAKARTA’S INTERNATIONAL ENGAGEMENT IN ADDRESSING COVID-19 PANDEMIC</a>
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</div></li>
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<li><strong>Restoring Protein Glycosylation with GlycoShape</strong> -
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<div>
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During the past few years we have been witnessing a revolution in structural biology. Leveraging on technological and computational advances, scientists can now resolve biomolecular structures at the atomistic level of detail by cryogenic electron microscopy (cryo-EM) and predict 3D structures from sequence alone by machine learning (ML). One technique often supports the other to provide the view of atoms in molecules required to capture the function of molecular machines. An example of the extraordinary impact of these advances on scientific discovery and on public health is given by how structural information supported the rapid development of COVID-19 vaccines based on the SARS-CoV-2 spike (S) glycoprotein. Yet, none of these new technologies can capture the details of the dense coat of glycans covering S, which is responsible for its natural, biologically active structure and function and ultimately for viral evasion. Indeed, glycosylation, the most abundant post-translational modification of proteins, is largely invisible through experimental structural biology and in turn it cannot be reproduced by ML, because of the lack of data to learn from. Molecular simulations through high-performance computing (HPC) can fill this crucial information gap, yet the computational resources, the users skills and the long timescales involved limit applications of molecular modelling to single study cases. To broaden access to structural information on glycans, here we introduce GlycoShape (https://glycoshape.org) an open access (OA) glycan structure database and toolbox designed to restore glycoproteins to their native functional form by supplementing the structural information available on proteins in public repositories, such as the RCSB PDB (www.rcsb.org) and AlphaFold Protein Structure Database (https://alphafold.ebi.ac.uk/), with the missing glycans derived from over 1 ms of cumulative sampling from molecular dynamics (MD) simulations. The GlycoShape Glycan Database (GDB) currently counts over 435 unique glycans principally covering the human glycome and with additional structures, fragments and epitopes from other eukaryotic and prokaryotic organisms. The GDB feeds into Re-Glyco, a bespoke algorithm in GlycoShape designed to rapidly restore the natural glycosylation to protein 3D structures and to predict N-glycosylation occupancy, where unknown. Ultimately, integration of GlycoShape with other OA protein structure databases can provide a much needed step-change in scientific discovery, from the structural and functional characterization of the active form of biomolecules, all the way down to pharmacological applications and drug discovery.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.11.571101v1" target="_blank">Restoring Protein Glycosylation with GlycoShape</a>
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<li><strong>Online holistic program to foster health amongst students: a pilot study in a Portuguese University during COVID-19 pandemic</strong> -
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During the COVID-19 pandemic, several preventive mental health interventions took place to increase the psychological well-being of university students due to the high levels of stress, anxiety and negative emotions experienced in that period. This context reinforced the role of universities in supporting students and preventing the mental health risk factors they faced. In this context a multidisciplinary team of professionals (psychologists, nurses, nutritionists, and artists) in the Portuguese Catholic University, gathered efforts and developed an holistic intervention program for university students based on a mind and body integrated approach. This program of 8 online sessions aims to improve students’ resilience to the psychosocial consequences of COVID-19 pandemic and promote their wellbeing. The twenty university students that participated in this pilot study reported that this intervention improved their emotional self-awareness, their ability to apply self-care strategies, as well as they believed it promoted healthier lifestyle changes. These findings suggest that this program consists in an innovative approach with the potential to promote the psychological health and well-being of university students in adverse circumstances.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/a2f5y/" target="_blank">Online holistic program to foster health amongst students: a pilot study in a Portuguese University during COVID-19 pandemic</a>
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<li><strong>Virological characteristics of the SARS-CoV-2 JN.1 variant</strong> -
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<div>
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The SARS-CoV-2 BA.2.86 lineage, first identified in August 2023, is phylogenetically distinct from the currently circulating SARS-CoV-2 Omicron XBB lineages, including EG.5.1 and HK.3. Comparing to XBB and BA.2, BA.2.86 carries more than 30 mutations in the spike (S) protein, indicating a high potential for immune evasion. BA.2.86 has evolved and its descendant, JN.1 (BA.2.86.1.1), emerged in late 2023. JN.1 harbors S:L455S and three mutations in non-S proteins. S:L455S is a hallmark mutation of JN.1: we have recently shown that HK.3 and other "FLip" variants carry S:L455F, which contributes to increased transmissibility and immune escape ability compared to the parental EG.5.1 variant. Here, we investigated the virological properties of JN.1.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.08.570782v1" target="_blank">Virological characteristics of the SARS-CoV-2 JN.1 variant</a>
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<li><strong>Distance to Vaccine Sites is Associated with Lower COVID-19 Vaccine Uptake</strong> -
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COVID-19 remains a leading cause of mortality in the U.S., despite widespread availability of vaccines. Conventional wisdom ties failure to vaccinate primarily to vaccine-skeptic beliefs (e.g., conspiracy theories, partisanship). Yet in this research, we find that vaccination is also hindered by travel distance to vaccine sites (a form of friction, or structural barriers). In study 1, Californians living farther from vaccine sites had lower vaccination rates, and this effect held regardless of partisanship. In study 2, Chicago zip codes saw an uptick in vaccination following vaccine site opening. These results proved robust in multiverse analyses accounting for a wide range of covariates, outcomes, and distance indicators. COVID-19 vaccination is hampered not just by vaccine hesitancy, but also structural barriers like distance. Efforts to boost vaccination could benefit from minimizing friction.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/mux5s/" target="_blank">Distance to Vaccine Sites is Associated with Lower COVID-19 Vaccine Uptake</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>IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS.</strong> - <b>Conditions</b>: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation <br/><b>Interventions</b>: Dietary Supplement: Nutritional blend (ImmuneRecov). <br/><b>Sponsors</b>: Federal University of São Paulo <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training</strong> - <b>Conditions</b>: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer <br/><b>Interventions</b>: Device: breathing training <br/><b>Sponsors</b>: Tri-Service General Hospital <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Physical Activity Coaching in Patients With Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active <br/><b>Sponsors</b>: University of Alcala; Professional College of Physiotherapists of the Community of Madrid <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID</strong> - <b>Conditions</b>: Long COVID; Post Acute Sequelae of COVID-19; Post-Acute COVID-19 <br/><b>Interventions</b>: Drug: Ensitrelvir; Other: Placebo <br/><b>Sponsors</b>: Timothy Henrich; Shionogi Inc. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Low-intensity Aerobic Training Associated With Global Muscle Strengthening in Post-COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Procedure: muscle strengthening <br/><b>Sponsors</b>: Centro Universitário Augusto Motta <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Intravenous Immunoglobulin Replacement Therapy for Persistent COVID-19 in Patients With B-cell Impairment</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: Immunoglobulins <br/><b>Sponsors</b>: Jaehoon Ko <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Inhaled Hydroxy Gas on Long COVID Symptoms</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Device: Hydroxy gas <br/><b>Sponsors</b>: Oxford Brookes University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community Care Intervention to Decrease COVID-19 Vaccination Inequities</strong> - <b>Conditions</b>: COVID-19 Vaccination <br/><b>Interventions</b>: Behavioral: Community Health Worker Intervention to Enhance Vaccination Behavior (CHW-VB) <br/><b>Sponsors</b>: RAND; Clinical Directors Network; National Institute on Minority Health and Health Disparities (NIMHD) <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PROmotion of COVID-19 BOOSTer VA(X)Ccination in the Emergency Department - PROBOOSTVAXED</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Vaccine Messaging; Behavioral: Vaccine Acceptance Question <br/><b>Sponsors</b>: University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Duke University; Baylor College of Medicine; Thomas Jefferson University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program for PASC Program to Improve Functioning of Persons Suffering From Post-COVID Syndrome: A Randomized Controlled Trial</strong> - <b>Conditions</b>: Post-Acute COVID-19; Post-Acute COVID-19 Syndrome; Post-Acute COVID-19 Infection; Long COVID; Long Covid19; Dyspnea; Orthostasis; Cognitive Impairment <br/><b>Interventions</b>: Other: Comprehensive Rehabilitation; Other: Augmented Usual Care <br/><b>Sponsors</b>: University of Pennsylvania; Medical College of Wisconsin; National Institutes of Health (NIH) <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>Multilevel Intervention of COVID-19 Vaccine Uptake Among Latinos</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Multilevel Intervention <br/><b>Sponsors</b>: San Diego State University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Stem Cell Study for Long COVID-19 Neurological Symptoms</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Biological: Stem Cell <br/><b>Sponsors</b>: Charles Cox; CBR Systems, Inc. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pursuing Reduction in Fatigue After COVID-19 Via Exercise and Rehabilitation (PREFACER): A Randomized Feasibility Trial</strong> - <b>Conditions</b>: Long-COVID; Long Covid19; Post-COVID-19 Syndrome; Post-COVID Syndrome; Fatigue <br/><b>Interventions</b>: Other: COVIDEx <br/><b>Sponsors</b>: Lawson Health Research Institute; Western University <br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An ncRNA transcriptomics-based approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes</strong> - CONCLUSION: Our novel in silico pipeline integrates effective methods from previous studies to predict and validate siRNA molecules, having the potential to inhibit viral replication pathway in vitro. In total, this study identified 17 highly specific siRNA molecules targeting NSP3, 4, and 6 and accessory genes ORF3a, 7a, 8, and 10 of SARS-CoV-2, which might be used as an additional antiviral treatment option especially in the cases of life-threatening urgencies.</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>Elevated peripheral levels of receptor-interacting protein kinase 1 (RIPK1) and IL-8 as biomarkers of human amyotrophic lateral sclerosis</strong> - Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to mediate pathogenesis of ALS. Primidone has been identified as an old drug that can also inhibit RIPK1 kinase. We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1^(G93A) mice and ALS patients. SOD1^(G93A) mice treated with primidone showed significant delay of symptomatic onset and improved…</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>Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies</strong> - We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active…</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>Enhancement efficiency delivery of antiviral Molnupiravir-drug via the loading with self-assembly nanoparticles of pycnogenol and cellulose which are decorated by zinc oxide nanoparticles for COVID-19 therapy</strong> - The target of the study is to modify the efficiency of Molnupiravir-drug (MOL) for COVID-19 therapy via the rearrangement of the building engineering of MOL-drug by loading it with self-assembly biomolecules nanoparticles (NPs) of pycnogenol (Pyc) and cellulose (CNC) which are decorated by zinc oxide nanoparticles. The synthesis and characterization of the modified drug are performing successfully, the loading and release process of the MOL drug on a nano surface is measured by UV-Vis…</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>Combating DC-SIGN-mediated SARS-CoV-2 dissemination by glycan-mimicking polymers</strong> - Many viruses exploit the human C-type lectin receptor dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) for cell entry and virus dissemination. An inhibition of DC-SIGN-mediated virus attachment by glycan-derived ligands has, thus, emerged as a promising strategy toward broad-spectrum antiviral therapeutics. In this contribution, several cognate fragments of oligomannose- and complex-type glycans grafted onto a poly-l-lysine scaffold are evaluated as polyvalent DC-SIGN ligands. 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>Discovery of High Affinity Cyclic Peptide Ligands for Human ACE2 with SARS-CoV-2 Entry Inhibitory Activity</strong> - The development of effective antiviral compounds is essential for mitigating the effects of the COVID-19 pandemic. Entry of SARS-CoV-2 virions into host cells is mediated by the interaction between the viral spike (S) protein and membrane-bound angiotensin-converting enzyme 2 (ACE2) on the surface of epithelial cells. Inhibition of this viral protein-host protein interaction is an attractive avenue for the development of antiviral molecules with numerous spike-binding molecules generated to…</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>Molybdenum Nanodots for Acute Lung Injury Therapy</strong> - Acute respiratory disease syndrome (ARDS) is a common critical disease with high morbidity and mortality rates, yet specific and effective treatments for it are currently lacking. ARDS was especially apparent and rampant during the COVID-19 pandemic. Excess reactive oxygen species (ROS) production and an uncontrolled inflammatory response play a critical role in the disease progression of ARDS. Herein, we developed molybdenum nanodots (MNDs) as a functional nanomaterial with ultrasmall size,…</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>Levocetrizine attenuates cyclophosphamide-induced lung injury through inhibition of TNF-α, IL-1β, TGF-β and MMP-9</strong> - Cyclophosphamide (CP) is an antineoplastic drug commonly used worldwide. Despite its spread, it causes fatal organ toxicity. Lung toxicity is a serious side effect of CP. Actually, in the past three years the world has been facing an un-predicted crisis following COVID-19 pandemic and the associated high-mortality rates attributed to respiratory distress. Accordingly; this study aimed to probe the potential prophylactic role of levocetrizine against CP-induced lung injury. Animals were allocated…</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>Peroxides Derivatives as SARS-CoV-2 Entry Inhibitors</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Host cell invasion is mediated by the interaction of the viral spike protein (S) with human angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD). In this work, bio-layer interferometry (BLI) was used to screen a series of fifty-two peroxides, including aminoperoxides and bridged 1,2,4 - trioxolanes (ozonides) classes, with the aim of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bile acids and bile acid activated receptors in the treatment of Covid-19</strong> - Since its first outbreak in 2020, the pandemic caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has caused the death of almost 7 million people worldwide. Vaccines have been fundamental in disease prevention and to reduce disease severity especially in patients with comorbidities. Nevertheless, treatment of COVID-19 has been proven difficult and several approaches have failed to prevent disease onset or disease progression, particularly in patients with comorbidities….</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>Antimicrobial activity of silver-copper coating against aerosols containing surrogate respiratory viruses and bacteria</strong> - The transmission of bacteria and respiratory viruses through expelled saliva microdroplets and aerosols is a significant concern for healthcare workers, further highlighted during the SARS-CoV-2 pandemic. To address this issue, the development of nanomaterials with antimicrobial properties for use as nanolayers in respiratory protection equipment, such as facemasks or respirators, has emerged as a potential solution. In this study, a silver and copper nanolayer called SakCu® was deposited on one…</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 ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV</strong> - The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting…</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>Analysis of SARS-CoV-2 Variant-Specific Serum Antibody Post-Vaccination Utilizing Immortalized Human Hepatocyte-Like Cells (HLC) to Assess Development of Immunity</strong> - CONCLUSION: HLC, along with AT-2 cells, provides a useful platform to study the development of neutralizing antibodies post-vaccination. Vaccination with the 3 available vaccines all elicited neutralizing serum antibodies that inhibited binding of each of the variant spike proteins to both AT-2 and HLC cells. This study suggests that inhibition of spike binding to target cells may be a more useful technique to assess immunity than gross quantitation of antibody.</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>Quercetin improves and protects Calu-3 airway epithelial barrier function</strong> - Introduction: In light of the impact of airway barrier leaks in COVID-19 and the significance of vitamin D in COVID-19 outcomes, including airway barrier protection, we investigated whether the very common dietary flavonoid quercetin could also be efficacious in supporting airway barrier function. Methods: To address this question, we utilized the widely used airway epithelial cell culture model, Calu-3. Results: We observed that treating Calu-3 cell layers with quercetin increased…</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>Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2</strong> - The pandemic caused by the coronavirus SARS-CoV-2 led to a global crisis in the world healthcare system. Despite some progress in the creation of antiviral vaccines and mass vaccination of the population, the number of patients continues to grow because of the spread of new SARS-CoV-2 mutations. There is an urgent need for direct-acting drugs capable of suppressing or stopping the main mechanisms of reproduction of the coronavirus SARS-CoV-2. Several studies have shown that the successful…</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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