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172 lines
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<title>10 November, 2022</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>COVID-19 Drug Percent Interaction: A python script for understanding drug network interactions</strong> -
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<div>
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In December 2019, a novel coronavirus initially surfaced in Wuhan, China, and it quickly spread around the world. The latest SARS-CoV-2 epidemic has generated major concerns about the hazards of emerging infectious viruses. COVID-19 outbreaks provide challenges for therapeutic medication therapies in the clinical context, as there is limited time for the discovery of novel therapeutics. One of the most practical methods for quickly creating medications for newly emerging and reemerging viruses is drug repurposing at the moment. COVID- 19 people who have underlying medical issues are at risk for drug-drug interactions because they take drugs repurposing. In order to overcome this difficulty, we take different drugs and their gene targets to understand the drug network interactions and its human protein interactions, SARS-CoV-2 infection processes, and drug targets in order to forecast novel drug-target interactions for COVID-19. Here, we present a python script, cli.py, combine_multiple_drugs_results.py, convert_to_edgelist.py, extract_interactions.py, find_interactor_or_node_in_network.py, parse_summaries.py, pipeline_parallel.py, pipeline.py and remove_duplicates.py, that efficiently tests the drug interactions of potential drug compounds against COVID-19.
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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/p82kf/" target="_blank">COVID-19 Drug Percent Interaction: A python script for understanding drug network interactions</a>
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</div></li>
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<li><strong>DrugDock Viral Module: Drug Repurposing via Comparing Target Drug Molecules with Covid-19 Antigens.</strong> -
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<div>
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The COVID-19 pandemic rapidly swept the world and to find an effective treatment was of the utmost importance, given the rate of infection and the subsequent number of deaths. Classical drug discovery pathways required multiple years to result in a usable product, which is why bioinformatic techniques such as molecular docking were given preference. To ensure a minimum number of lives were lost, drugs that existed prior to Covid were screened to see which ones could be used as treatment. Screening through these drugs individually through pre-existing docking methods would be a tedious process. Ensuring each drug to be screened has a chemical structure that would effectively bind to the SARS-CoV-2 spike proteins would extend the drug repurposing process by precious years. To circumvent this, we have created the python script below, that utilizes the SMILES structures of drugs, as well as docking techniques to provide ease of screening for target drug molecules. Below, the python script clip.py is elucidated, that is able to accept input in the form of a drug name, or a structured data file; which it then compares to the preprogrammed viral antigens. The output is then a table of the docking affinities of the drug or sdfs file with each antigen as well as the ligands that have the most affinity.
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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/hdpbw/" target="_blank">DrugDock Viral Module: Drug Repurposing via Comparing Target Drug Molecules with Covid-19 Antigens.</a>
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</div></li>
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<li><strong>Cli.py: A python script for automating the docking results to create a Knowledge Graph</strong> -
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<div>
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The recent SARS-CoV-2 epidemic has brought to light significant concerns regarding the dangers of new infectious viruses. having limited time for the creation of new medications. In the clinical domain, the outbreak presents difficulties for therapeutic pharmacological therapy. While there are numerous clinical studies being conducted to treat Covid-19, the approach of molecular docking is commonly being employed for drug screening. The use of molecular docking in drug repurposing techniques shows significant possibilities. The application of docking enables the identification of new pharmaceutical compounds, the molecular prediction of ligand-target interactions, and the understanding of structure-activity linkages. The provided script enabled the creation of an independent docking module which offers a method to automate the docking results and enable the highest binding affinity with 3D models based on the drug-target interactions. Here, we present a python script, cli.py, that efficiently represents a knowledge graph based on docking of the drug targets, AAK1, GAK and JAK1/2.
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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://osf.io/6xjkb/" target="_blank">Cli.py: A python script for automating the docking results to create a Knowledge Graph</a>
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</div></li>
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<li><strong>I’ve Been Thinkin’ Bout You: Socially Distant Relationship Pursuit during COVID-19</strong> -
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<div>
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The COVID-19 pandemic has radically altered everyday interactions, potentially disrupting the process of romantic relationship formation. Prior research suggests that threats to the basic psychological need for relatedness, along with negative mental imagery, can lead to an obsessive preoccupation with a romantic target. We investigated how the relatedness-threatening nature of the pandemic may similarly facilitate problematic relationship behaviors—specifically presumptuous romantic intentions. We present two studies—a small-scale natural experiment with measurements before and during the pandemic (Study 1), as well as a daily diary study (Study 2)—during two different waves of the COVID-19 pandemic to understand how relatedness threats and negative fantasies predict presumptuous romantic intentions. In Study 1 these threats unexpectedly corresponded to reduced presumptuous romantic intentions, though no such main effect was present in Study 2. Replicating prior experimental work, in both studies, we found evidence that more negative fantasies about a romantic target predicted greater presumptuous romantic intentions. Study 2 also revealed that at the between-person level the combinatory effect of need threat and negative fantasies lead to greater intentions. At the within-person level, this combinatory effect led unexpectedly to reduced intentions. Finally, we observed heterogeneity in the within-person effect of COVID-induced relatedness threat: although relatedness threat stoked intentions for some individuals, for others it reduced intentions. Our work suggests that for many, the early social ramifications of COVID-19 reduced motivation to presumptuously pursue romantic relationships. Yet, certain individuals, particularly those with more negative fantasies, are more prone to pursue presumptuously amidst 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://psyarxiv.com/g6nhk/" target="_blank">I’ve Been Thinkin’ Bout You: Socially Distant Relationship Pursuit during COVID-19</a>
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</div></li>
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<li><strong>DrugDock Viral Module: Drug Repurposing via Comparing Target Drug Molecules with Covid-19 Antigens.</strong> -
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<div>
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The COVID-19 pandemic rapidly swept the world and to find an effective treatment was of the utmost importance, given the rate of infection and the subsequent number of deaths. Classical drug discovery pathways required multiple years to result in a usable product, which is why bioinformatic techniques such as molecular docking were given preference. To ensure a minimum number of lives were lost, drugs that existed prior to Covid were screened to see which ones could be used as treatment. Screening through these drugs individually through pre-existing docking methods would be a tedious process. Ensuring each drug to be screened has a chemical structure that would effectively bind to the SARS-CoV-2 spike proteins would extend the drug repurposing process by precious years. To circumvent this, we have created the python script below, that utilizes the SMILES structures of drugs, as well as docking techniques to provide ease of screening for target drug molecules. Below, the python script clip.py is elucidated, that is able to accept input in the form of a drug name, or a structured data file; which it then compares to the preprogrammed viral antigens. The output is then a table of the docking affinities of the drug or sdfs file with each antigen as well as the ligands that have the most affinity.
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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/c7frh/" target="_blank">DrugDock Viral Module: Drug Repurposing via Comparing Target Drug Molecules with Covid-19 Antigens.</a>
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</div></li>
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<li><strong>SARS-CoV-2 ORF8 limits expression levels of Spike antigen.</strong> -
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<div>
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Survival from COVID-19 depends on the ability of the host to effectively neutralize virions and infected cells, a process largely driven by antibody-mediated immunity. However, with the newly emerging variants that evade Spike-targeting antibodies, re-infections and breakthrough infections are increasingly common. A full characterization of SARS-CoV-2 mechanisms counteracting antibody-mediated immunity is needed. Here, we report that ORF8 is a SARS-CoV-2 factor that controls cellular Spike antigen levels. ORF8 limits the availability of mature Spike by inhibiting host protein synthesis and retaining Spike at the endoplasmic reticulum, reducing cell-surface Spike levels and recognition by anti-SARS-CoV-2 antibodies. With limited Spike availability, ORF8 restricts Spike incorporation during viral assembly, reducing Spike levels in virions. Cell entry of these virions leaves fewer Spike molecules at the cell surface, limiting antibody recognition of infected cells. Our studies propose an ORF8-dependent SARS-CoV-2 strategy that allows immune evasion of infected cells for extended viral production.
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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/10.1101/2022.11.09.515752v1" target="_blank">SARS-CoV-2 ORF8 limits expression levels of Spike antigen.</a>
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</div></li>
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<li><strong>Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages</strong> -
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<div>
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The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better un-derstanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fit-ness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 [≥] BA.2 [≥] BA.2.12.1 > BA.1; no difference in body weight loss was observed among differ-ent sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice de-veloped distinguisable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e., USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titers did not always correlate with viral replication levels in infected animals. Our results reveal distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.
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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/10.1101/2022.11.08.515725v1" target="_blank">Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages</a>
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</div></li>
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<li><strong>Impact of variants of concern on SARS-CoV-2 viral dynamics in non-human primates.</strong> -
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<div>
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The impact of variants of concern (VoC) on SARS-CoV-2 viral dynamics remains poorly understood and essentially relies on observational studies subject to various sorts of biases. In contrast, experimental models of infection constitute a powerful model to perform controlled comparisons of the viral dynamics observed with VoC and better quantify how VoC escape from the immune response. Here we used molecular and infectious viral load of 78 cynomolgus macaques to characterize in detail the effects of VoC on viral dynamics. We first developed a mathematical model that recapitulate the observed dynamics, and we found that the best model describing the data assumed a rapid antigen-dependent stimulation of the immune response leading to a rapid reduction of viral infectivity. When compared with the historical variant, all VoC except beta were associated with an escape from this immune response, and this effect was particularly sensitive for delta and omicron variant (p<10-6 for both). Interestingly, delta variant was associated with a 1.8-fold increased viral production rate (p=0.046), while conversely omicron variant was associated with a 14-fold reduction in viral production rate (p<10-6). During a natural infection, our models predict that delta variant is associated with a higher peak viral RNA than omicron variant (7.6 log10 copies/mL 95% CI 6.8 - 8 for delta; 5.6 log10 copies/mL 95% CI 4.8 - 6.3 for omicron) while having similar peak infectious titers (3.7 log10 PFU/mL 95% CI 2.4 - 4.6 for delta; 2.8 log10 PFU/mL 95% CI 1.9 - 3.8 for omicron). These results provide a detailed picture of the effects of VoC on total and infectious viral load and may help understand some differences observed in the patterns of viral transmission of these viruses.
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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/10.1101/2022.11.09.515748v1" target="_blank">Impact of variants of concern on SARS-CoV-2 viral dynamics in non-human primates.</a>
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</div></li>
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<li><strong>Circulating proteome of hospitalized patients uncovers six endophenotypes of COVID-19 and points to FGFR and SHC4-signaling in acute respiratory distress syndrome</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Defining the molecular mechanisms of novel diseases such as COVID-19 is crucial to identify treatable traits to improve patient care. To circumvent a priori bias and the lack of in-depth knowledge of this new disease, we opted for an unsupervised stratification approach, followed by detailed multi-modal characterization using proteome, metabolomic, genomic, and clinical features. Using the detailed circulating proteome, as measured by 4985 aptamers (SOMAmers), robust consensus clustering identified six endophenotypes (EPs) present among 731 SARS-CoV-2 PCR-positive hospitalized participants to Biobanque québécoise de la COVID-19 (BQC19), with varying degrees of disease severity and times to intensive care unit (ICU) admission. In particular, one endophenotype, EP6, was associated with a greater proportion of ICU admission, mechanical ventilation, acute respiratory distress syndrome (ARDS) and death. Clinical features of this endophenotype showed increased levels of C-reactive protein, D-dimers, elevated neutrophils, and depleted lymphocytes. Moreover, metabolomic analysis supported a role for immuno-thrombosis in severe COVID-19 ARDS. Furthermore, Fibroblast Growth Factor Receptor (FGFR) and SH2-containing transforming protein 4 (SHC4) signaling were identified as molecular features associated with severe COVID-19. Importantly, a predictive model was developed and validated on an additional set of 631 SARS-CoV-2 PCR-positive patients to enable prediction of these endophenotypes, which reflect patients9 likelihood of admission to ICU, solely based on clinical laboratory measurements. This suggests the use of blood markers as surrogates for generalizing these EPs to new patients and automating identification of high-risk groups in the clinic.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.02.22281834v2" target="_blank">Circulating proteome of hospitalized patients uncovers six endophenotypes of COVID-19 and points to FGFR and SHC4-signaling in acute respiratory distress syndrome</a>
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</div></li>
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<li><strong>World Health Organization Is Losing Public Credibility Towards Health-Sensitive Topics: Infodemiological Analysis of Facebook Users’ Reactions</strong> -
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<div>
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Background The scientific infodemic constitutes one of the greatest threats to public health and safety today. The credibility of the main dissemination agencies is an essential tool for adhering to measures to preserve public health. Methods Reactions such as “like,” “love,” “affection,” “surprise,” “sadness,” “anger,” and “derision” were collected under World Health Organization Facebook posts on climate change (from 2019 to 2022) and vaccines (from 2021 to 2022). Descriptive statistics, linear regression, and correlation methods were implemented to identify possible trends and causal relationships with the COVID-19 vaccination campaign. Results These findings showed a worrying increase in derision reactions about climate change-related posts (up to 22% in November 2022, with a quadratically growing trend over time since December 2020). Furthermore, infodemic reactions such as anger and especially derision made up the majority of emotional reactions to vaccine-related posts since 2021 and up to 44% of total reactions in November 2022 (median since July 2021 = 9%, IQR: 4% - 14 %). Finally, there is evidence of a causal correlation between the start of the COVID-19 vaccination campaign and public distrust towards the WHO, even for issues unrelated to vaccines such as climate change. Conclusion These findings signal that the World Health Organization is losing public credibility towards extremely relevant issues for global health. Infodemiological interventions in accordance with the recent literature are urgently required.
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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/t37xd/" target="_blank">World Health Organization Is Losing Public Credibility Towards Health-Sensitive Topics: Infodemiological Analysis of Facebook Users’ Reactions</a>
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</div></li>
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<li><strong>Reconstruction of the People’s Economic Model: Development of Micro, Small and Medium Businesses Based on Digital Transformation as a Strengthening Economy Post-Covid-19 Pandemic</strong> -
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<div>
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The people’s economy is one of the principle instruments of Indonesian economic democracy. To overcome economic conditions during the Covid-19 pandemic, people are motivated to overcome problems to meet their needs for life independently. Communities and digital-based small and medium enterprises have unwittingly formed a mutually beneficial relationship between business transactions. The concept of populist economy is re-actualized in their economic activities. This study aims to examine the reconstruction of the populist economic model as the development of small and medium-sized businesses based on digital transformation in a post-covid-19 pandemic. This research is a literature study with descriptive-analytic research specifications. The results of the study show that the concept of a populist economy and digital transformation in small businesses is a model for strengthening the populist economy during the COVID-19 pandemic, but it has not yet been measured regarding the sustainability of the model’s reconstruction after the pandemic. This concept can become a new paradigm in order to strengthen the national economy after the COVID-19 pandemic.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/rvk4t/" target="_blank">Reconstruction of the People’s Economic Model: Development of Micro, Small and Medium Businesses Based on Digital Transformation as a Strengthening Economy Post-Covid-19 Pandemic</a>
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</div></li>
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<li><strong>Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture</strong> -
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<div>
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In an effort to identify therapeutic intervention strategies for the treatment of COVID-19, we have investigated a selection of FDA-approved small molecules and biologics that are commonly used to treat other human diseases. A investigation into 18 small molecules and 3 biologics was conducted in cell culture and the impact of treatment on viral titer was quantified by plaque assay. The investigation identified 4 FDA approved small molecules, Maraviroc, FTY720 (Fingolimod), Atorvastatin and Nitazoxanide that were able to inhibit SARS-CoV-2 infection. Confocal microscopy with over expressed S-protein demonstrated that Maraviroc reduced the extent of S-protein mediated cell fusion as observed by fewer multinucleate cells in the context of drug-treatment. Mathematical modeling of drug-dependent viral multiplication dynamics revealed that prolonged drug treatment will exert an exponential decrease in viral load in a multicellular/tissue environment. Taken together, the data demonstrate that Maraviroc, Fingolimod, Atorvastatin and Nitazoxanide inhibit SARS-CoV-2 in cell culture.
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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/10.1101/2020.08.12.246389v2" target="_blank">Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture</a>
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</div></li>
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<li><strong>Pathology and Anticatalysis treatment of exacerbated COVID-19</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated diseases whose pathophysiology involves the sterile alpha motif (SAM) and histidine-aspartate domain (HD)-containing protein 1 (SAMHD1) tetramerization and cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)– stimulator of interferon genes (STING) signalling pathway, angiotensin-converting enzyme 2 (ACE2), Toll-like receptor 2 (TLR2), and Toll-like receptor 4 (TLR4) pathway with high LPS levels in the blood, inflammasome–spike protein–genetic activation pathway, and innate lymphoid cells with Neuropilin‑1 Pathway. They exacerbated COVID-19 type I interferonopathies, and it is necessary to prescribe anticatalytic treatments to alleviate the pathologic course and take the lag time to coordinate innate or adaptive immune cell reactions.
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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/t9wjz/" target="_blank">Pathology and Anticatalysis treatment of exacerbated COVID-19</a>
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</div></li>
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<li><strong>Optimization of the Illumina COVIDSeq™ protocol for decentralized, cost-effective genomic surveillance</strong> -
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<div>
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A decentralized surveillance system to identify local outbreaks and monitor SARS-CoV-2 Variants of Concern is one of the primary strategies for the pandemic’s containment. Although next-generation sequencing (NGS) is a gold standard for genomic surveillance and variant discovery, the technology is still cost-prohibitive for decentralized sequencing, particularly in small independent labs with limited resources. We have optimized the Illumina COVID-seq protocol to reduce cost without compromising accuracy. 90% of genomic coverage was achieved for 142/153 samples analyzed in this study. The lineage was correctly assigned to all samples (152/153) except for one. This modified protocol can help laboratories with constrained resources contribute to decentralized SARS-CoV-2 surveillance in the post-vaccination era.
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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/10.1101/2022.11.07.515545v1" target="_blank">Optimization of the Illumina COVIDSeq™ protocol for decentralized, cost-effective genomic surveillance</a>
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</div></li>
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<li><strong>Normalized Semi-Covariance Co-Efficiency Analysis of Spike Proteins from SARS-CoV-2 variant Omicron and Other Coronaviruses for their Infectivity and Virulence</strong> -
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<div>
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Spectrum-based Mass-Charge modeling is increasingly used in biological analysis. To explain statistical phenomenon with positive and negative fluctuations of amino acid charges in spike protein sequences from Omicron and other coronaviruses, we propose calculation-based Mass-Charge modeling, a normalized derivation algorithm with exact Excel and MATLAB tool involving separate quadrant extension to normalized covariance, which is still compatible with Pearson covariance co-efficiency. The number of amino acids, molecular weight, isoelectric point, amino acid composition, charged residues, mass-charge ratio, hydropathicity of the proteins were taken into consideration in the analyses, and the relative peak and dip of the average with spike protein sequences based on hydrophobic mass to isoelectric charges of amino acids were also examined. The analyses with the algorithm provide more clear insights leading to revealing underline evolving trends of the viral proteins. Spike proteins from SARS-CoV-2 variants, seasonal and murine coronaviruses were taken as representative examples in this study. The analyses demonstrate that the Mass-Charge covariance co-efficiency can distinguish subtle differences between biological properties of spike proteins and correlate well with viral infectivity and virulence.
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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/10.1101/2022.11.07.515557v1" target="_blank">Normalized Semi-Covariance Co-Efficiency Analysis of Spike Proteins from SARS-CoV-2 variant Omicron and Other Coronaviruses for their Infectivity and Virulence</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Bivalent Booster Megastudy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Multi-Level Multi-Component Intervention (MLI); Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<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>Safety and Efficacy of Medications COVID-19</strong> - <b>Condition</b>: Severe Covid-19<br/><b>Intervention</b>: Drug: Oral bedtime melatonin<br/><b>Sponsor</b>: Hospital San Carlos, Madrid<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>Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma<br/><b>Sponsors</b>: Hospital Regional Dr. Rafael Estévez; Complejo Hospitalario Dr. Arnulfo Arias Madrid; Hospital Santo Tomas; Hospital Punta Pacífica, Pacífica Salud; Insituto Conmemorativo Gorgas de Estudios para la Salud; Sociedad Panameña de Hematología; Institute of Scientific Research and High Technology Services (INDICASAT AIP); University of Panama; Sistema Nacional de Investigación de Panamá<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>Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Facilitated Self-Sampling Intervention (FSSI); Behavioral: Testing Navigation Intervention (TNI).; Behavioral: Control<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<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>Assessing Performance of the Testing Done Simple Covid 19 Antigen Test</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Testing Done Simple SARS CoV-2 Antigen Test<br/><b>Sponsors</b>: Testing Done Simple; Nao Medical Urgent Care<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: EuCorVac-19; Biological: ChAdOx1<br/><b>Sponsor</b>: EuBiologics 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>Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Molnupiravir (Esperavir); Drug: Standard of care<br/><b>Sponsor</b>: Promomed, LLC<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>Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir/ritonavir; Drug: Standard of care<br/><b>Sponsors</b>: Promomed, LLC; Sponsor GmbH<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead Sciences<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>Effects of Respiratory Muscle Training in Individuals With Long-term Post-COVID-19 Symptoms</strong> - <b>Conditions</b>: Covid19; Post-acute COVID-19 Syndrome<br/><b>Interventions</b>: Other: Inspiratory + expiratory muscle training group; Other: Inspiratory + expiratory muscle training sham group; Other: Exercise training program<br/><b>Sponsors</b>: Universidad Complutense de Madrid; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid<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>Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial</strong> - <b>Conditions</b>: COVID-19; Coronavirus Infections<br/><b>Interventions</b>: Biological: LIBP-Rec-Vaccine; Biological: BIBP-Rec-Vaccine; Biological: placebo<br/><b>Sponsors</b>: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza</strong> - <b>Conditions</b>: Influenza, Human; COVID-19<br/><b>Interventions</b>: Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5); Biological: qIRV (22/23); Biological: QIV<br/><b>Sponsors</b>: BioNTech SE; Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate Safety, Tolerability, Efficacy and Pharmacokinetics of ASC10 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: SARS CoV 2 Infection<br/><b>Interventions</b>: Drug: ASC10; Drug: Placebo<br/><b>Sponsor</b>: Ascletis Pharmaceuticals Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GLB-COV2-043; Drug: BNT162b2/COMIRNATY®<br/><b>Sponsor</b>: GreenLight Biosciences, Inc.<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>Structural similarities between SARS-CoV2 3CL<sup>pro</sup> and other viral proteases suggest potential lead molecules for developing broad spectrum antivirals</strong> - Considering the significant impact of the recent COVID-19 outbreak, development of broad-spectrum antivirals is a high priority goal to prevent future global pandemics. Antiviral development processes generally emphasize targeting a specific protein from a particular virus. However, some antiviral agents developed for specific viral protein targets may exhibit broad spectrum antiviral activity, or at least provide useful lead molecules for broad spectrum drug development. There is significant…</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>Malondialdehyde acetaldehyde-adduction of surfactant protein D attenuates SARS-CoV-2 spike protein binding and virus neutralization</strong> - CONCLUSIONS: Overall, MAA-adduction of SPD, a consequence of alcohol overconsumption, represents one mechanism of compromised lung innate defense against SARS-CoV-2, highlighting a possible mechanism underlying COVID-19 severity and related mortality in patients who misuse alcohol.</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>Linoleic acid binds to SARS-CoV-2 RdRp and represses replication of seasonal human coronavirus OC43</strong> - Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficacy. However, little is yet known about their effect on replication of human coronaviruses. To shed light on this subject, we first screened 15 fatty acids, three lipid-soluble vitamins, and cholesterol, on SARS-CoV-2 RdRp, and identified the four fatty acids with the highest RdRp inhibitory potential. Among them, linoleic acid was found to have the greatest interaction with SARS-CoV-2 RdRp, with its…</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>Implementation of a Virtual Asynchronous Scribe Program to Reduce Physician Burnout</strong> - GOAL: Administrative burden is one of many potential root causes of physician burnout. Scribe documentation assistance can reduce this burden. However, traditional in-person scribe services are challenged by consistent staffing because the model requires the physical presence of a scribe and limits the team to a single individual. In addition, in-person scribes cannot provide the flexible support required for virtual care encounters, which can now pivot geographically and temporally. To respond…</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>Current Approaches to COVID-19 Drug Discovery and Safety Assessment</strong> - Various methods currently being explored to treat COVID-19 were discussed during a symposium at the Fall 2022 ACS conference. These methods included the inhibiting of immune responses and viral replication pathways as well as repurposing known 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>Two-helix supramolecular proteomimetic binders assembled via PNA-assisted disulfide cross-linking</strong> - Peptidic motifs folded in a defined conformation are able to inhibit protein-protein interactions (PPIs) covering large interfaces and as such they are biomedical molecules of interest. Mimicry of such natural structures with synthetically tractable constructs often requires complex scaffolding and extensive optimization to preserve the fidelity of binding to the target. Here, we present a novel proteomimetic strategy based on a 2-helix binding motif that is brought together by hybridization 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>Determination of Binding Affinity of Tunicamycin with SARS-CoV-2 Proteins: Proteinase, Protease, nsp2, nsp9, ORF3a, ORF7a, ORF8, ORF9b, Envelope and RBD of Spike Glycoprotein</strong> - Introduction: Despite the availability of several COVID-19 vaccines, the incidence of infections remains a serious issue. Tunicamycin (TM), an antibiotic, inhibited tumor growth, reduced coronavirus envelope glycoprotein subunit 2 synthesis, and decreased N-linked glycosylation of coronavirus glycoproteins. Objectives: Our study aimed to determine how tunicamycin interacts with certain coronavirus proteins (proteinase, protease, nsp9, ORF7a, ORF3a, ORF9b, ORF8, envelope protein, nsp2, and RBD 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>Environmental Impacts on COVID-19: Mechanisms of Increased Susceptibility</strong> - CONCLUSIONS: Exposure to particulate matter (PM) pollution enhanced morbidity and mortality to COVID-19 in a pediatric population associated with induction of oxidative stress. In addition, free radicals present on PM can induce rapid changes in the viral genome that can lead to vaccine escape, altered host susceptibility, and viral pathogenicity. Nutritional antioxidant supplements have been shown to reduce the severity of viral infections, inhibit the inflammatory cytokine storm, and boost…</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>Hippo signaling pathway activation during SARS-CoV-2 infection contributes to host antiviral response</strong> - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the Coronavirus Disease 2019 (COVID-19) pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk of vaccine failures and prolongation of the pandemic. However, our understanding of the molecular basis of SARS-CoV-2 infection and subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered a critical role for the evolutionarily conserved…</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>Potential usefulness of Mediterranean diet polyphenols against COVID-19-induced inflammation: a review of the current knowledge</strong> - The Mediterranean diet is a dietary pattern typical of the populations living in the Mediterranean basin during the 50s-60s of the last century. This diet has demonstrated beneficial effects in the prevention of several pathologies such as cardiovascular diseases, metabolic syndrome, or several cancer types, at least in part, due to its antioxidant compounds. Since the COVID-19 pandemic started, different authors have been studying the effects of certain dietary habits on the presence 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>Automated detection of neutralizing SARS-CoV-2 antibodies in minutes using a competitive chemiluminescence immunoassay</strong> - The SARS-CoV-2 pandemic has shown the importance of rapid and comprehensive diagnostic tools. While there are numerous rapid antigen tests available, rapid serological assays for the detection of neutralizing antibodies are and will be needed to determine not only the amount of antibodies formed after infection or vaccination but also their neutralizing potential, preventing the cell entry of SARS-CoV-2. Current active-virus neutralization assays require biosafety level 3 facilities, while…</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>The Quest for mRNA Vaccines</strong> - The success of mRNA vaccines against COVID-19 is nothing short of a medical revolution. Given its chemical lability the use of mRNA as a therapeutic has been counterintuitive and met with skepticism. The development of mRNA-based COVID-19 vaccines was the culmination of long and painstaking efforts by many investigators spanning over 30 years and culminating with the seminal studies of Kariko and Weissman. This review will describe one chapter in this saga, studies that have shown that mRNA can…</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>Respiratory Syncytial Virus Two-Step Infection Screen Reveals Inhibitors of Early and Late Life Cycle Stages</strong> - Human respiratory syncytial virus (hRSV) infection is a leading cause of severe respiratory tract infections. Effective, directly acting antivirals against hRSV are not available. We aimed to discover new and chemically diverse candidates to enrich the hRSV drug development pipeline. We used a two-step screen that interrogates compound efficacy after primary infection and a consecutive virus passaging. We resynthesized selected hit molecules and profiled their activities with hRSV lentiviral…</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>Advances And Challenges In Using Nirmatrelvir And Its Derivatives Against Sars-Cov-2 Infection</strong> - On 22 December 2021, the United States Food and Drug Administration (FDA) approved the first M^(pro) inhibitor, i.e., oral antiviral nirmatrelvir (PF-07321332)/ritonavir (Paxlovid), for the treatment of early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nirmatrelvir inhibits SARS-CoV-2 infection, but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression. The chiral structure of nirmatrelvir plays a key role 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>Protocol for characterizing the inhibition of SARS-CoV-2 infection by a protein of interest in cultured cells</strong> - Here, we present a protocol to characterize the antiviral ability of a protein of interest to SARS-CoV-2 infection in cultured cells, using MUC1 as an example. We use SARS-CoV-2 ΔN trVLP system, which utilizes transcription and replication-competent SARS-CoV-2 virus-like particles lacking nucleocapsid gene. We describe the optimized procedure to analyze protein interference of viral attachment and entry into cells, and qRT-PCR-based quantification of viral infection. The protocol can be applied…</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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