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183 lines
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<title>07 March, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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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<li><strong>Will Europe be forged in crises? The impact of the Covid-19 and Ukraine crises on EU actorness</strong> -
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<div>
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In this paper, we study the effect of crises on EU actorness, defined as the EU’s capacity to defend its interests and values at the global level. Our research focuses on two major crises, the Covid-19 crisis and the 2022 Russian invasion of Ukraine. Drawing on a process-tracing approach, we analyse four of the Union’s policy initiatives that were proposed, negotiated and implemented to respond to these crises: joint vaccine procurement, common gas purchases, and the COVAX and FARM initiatives. The paper assesses the outcomes of these four initiatives and discusses the extent to which these initiatives led to the development of EU actorness and the achievement of common objectives. The analysis identifies the degree of internal cohesion, and how it is influenced by specific crises, as a key factor in fostering or hampering EU actorness in different policy fields. It also shows that the formal distribution of competences between the EU and the member states in specific policy areas matters little in crisis times, as the EU can resort to emergency competences in such situations. The findings of this paper contribute to the literature on EU actorness and equally provide some insights on policy legacies and learning.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/c3zwt/" target="_blank">Will Europe be forged in crises? The impact of the Covid-19 and Ukraine crises on EU actorness</a>
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</div></li>
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<li><strong>Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae</strong> -
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By largely unknown mechanism(s), SARS-CoV-2 hijacks the host translation apparatus to promote COVID-19 pathogenesis. We report that the histone methyltransferase G9a noncanonically regulates viral hijacking of the translation machinery to bring about COVID-19 symptoms of hyperinflammation, lymphopenia, and blood coagulation. Chemoproteomic analysis of COVID-19 patient peripheral mononuclear blood cells (PBMC) identified enhanced interactions between SARS-CoV-2-upregulated G9a and distinct translation regulators, particularly the N6-methyladenosine (m6A) RNA methylase METTL3. These interactions with translation regulators implicated G9a in translational regulation of COVID-19. Inhibition of G9a activity suppressed SARS-CoV-2 replication in human alveolar epithelial cells. Accordingly, multi-omics analysis of the same alveolar cells identified SARS-CoV-2-induced changes at the transcriptional, m6A-epitranscriptional, translational, and post-translational (phosphorylation or secretion) levels that were reversed by inhibitor treatment. As suggested by the aforesaid chemoproteomic analysis, these multi-omics-correlated changes revealed a G9a-regulated translational mechanism of COVID-19 pathogenesis in which G9a directs translation of viral and host proteins associated with SARS-CoV-2 replication and with dysregulation of host response. Comparison of proteomic analyses of G9a inhibitor-treated, SARS-CoV-2 infected cells, or ex vivo culture of patient PBMCs, with COVID-19 patient data revealed that G9a inhibition reversed the patient proteomic landscape that correlated with COVID-19 pathology/symptoms. These data also indicated that the G9a-regulated, inhibitor-reversed, translational mechanism outperformed G9a-transcriptional suppression to ultimately determine COVID-19 pathogenesis and to define the inhibitor action, from which biomarkers of serve symptom vulnerability were mechanistically derived. This cell line-to-patient conservation of G9a-translated, COVID-19 proteome suggests that G9a inhibitors can be used to treat patients with COVID-19, particularly patients with long-lasting COVID-19 sequelae.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.04.583415v1" target="_blank">Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae</a>
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</div></li>
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<li><strong>MORTALITY-ASSOCIATED SARS-COV-2 GENOMIC VARIANTS FROM PATIENTS HOSPITALIZED FOR SEVERE PNEUMONIA IN AGUASCALIENTES, MEXICO FROM 2020 TO 2023</strong> -
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The SARS-CoV-2 virus has caused a global health crisis, resulting in a significant loss of human lives. It is essential to report disease and mutation associations to provide ideas for public health interventions and preventive measures. In this study, to determine the association between genomic variants and the severity of pneumonia caused by SARS-CoV-2, a sequencing analysis of 150 patient samples with confirmed COVID-19 was conducted. These samples were collected between 2021 and 2023 and isolated in Aguascalientes, Mexico. The patient cohort had males and females ranging from 0 to 91 years old. Males accounted for 66% of the population analyzed. The Delta variant was the most prevalent lineage associated with deaths in 2021-2022, while the B.1.1.529 lineages emerged in mid-2022. Currently, the XBB lineage is the most commonly identified in Mexico. New mutations L95M and L46M in ORF 8 and ORF 9 were discovered in 30% and 20% of the sequences and are uniquely present in the studied population. These mutations are positively associated with patient death. This study provides valuable data to aid in understanding the evolution of SARS-CoV-2 in specific populations and explores the severity of the disease and mutation correlations.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.05.583594v1" target="_blank">MORTALITY-ASSOCIATED SARS-COV-2 GENOMIC VARIANTS FROM PATIENTS HOSPITALIZED FOR SEVERE PNEUMONIA IN AGUASCALIENTES, MEXICO FROM 2020 TO 2023</a>
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<li><strong>Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants</strong> -
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The open reading frame 8 (ORF8), an accessory protein of SARS-CoV-2, is prone to deletions and mutations across different viral variants, which was first described in several Singapore variants. The reason why viral evolution favors loss or inactivation of ORF8 is not fully understood, although the effects of ORF8 on inflammation, immune evasion, and disease severity have been described. Here we show using clinical ORF8 deficient viral isolates, virus like particles (VLPs) and viral replicons that ORF8 expression dampens viral particle production. ORF8 physically interacts with the viral Spike protein and induces Golgi fragmentation, overall contributing to less virus particle production. Using systematic ORF8 deletions, we mapped the particle reducing function to its N terminal signal peptide. Interestingly, this part of ORF8 is severely truncated in the recent XBB.1.5 variant, and when restored, suppresses viral particle production in the context of the entire viral genome. Collectively, our data support the model that evolutionary pressure exists to delete ORF8 sequence and expression across SARS-CoV-2 variants to fully enable viral particle production.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.05.583578v1" target="_blank">Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants</a>
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<li><strong>The Global Impact of COVID-19 on Tuberculosis: A Thematic Scoping Review, 2020-2023</strong> -
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Background: This thematic scoping review of publications sought to understand the global impact of COVID-19 on tuberculosis (TB), interpret the scope of resonating themes, and offer policy recommendations to stimulate TB recovery and future pandemic preparedness. Data Sources: Publications were captured from three search engines, PubMed, EBSCO, and Google Scholar, and applicable websites written in English from January 1, 2020, to April 30, 2023. Study Selection: Our scoping review was limited to publications detailing the impact of COVID-19 on TB. Original research, reviews, letters, and editorials describing the deleterious and harmful––yet sometimes positive–– impact of COVID-19 (sole exposure) on TB (sole outcome) were included. The objective was to methodically categorize the impacts into themes through a comprehensive review of selected studies to provide significant health policy guidance. Data Extraction: Two authors independently screened citations and full texts, while the third arbitrated when consensus was not met. All three performed data extraction. Data Synthesis/Results: Of 1,755 screened publications, 176 (10%) covering 39 countries over 41 months met the inclusion criteria. Ten principal themes were established, which encompassed TB’s care cascade, patient-centered care, psychosocial issues, and health services: 1) case-finding and notification (n=45; 26%); 2) diagnosis and laboratory systems (n=19; 10.7%) 3) prevention, treatment, and care (n=22; 12.2%); 4) telemedicine/telehealth (n=12; 6.8%); 5) social determinants of health (n=14; 8%); 6) airborne infection prevention and control (n=8; 4.6%); 7) health system strengthening (n=22; 13%); 8) mental health (n=13; 7.4%); 9) stigma (n=11; 6.3%); and 10) health education (n=10; 5.7%). Limitations: Heterogeneity of publications within themes. Conclusions: We identified ten globally generalizable themes of COVID-19’s impact on TB. These thematic areas will guide evidence-informed policies to strengthen comprehensive global responses, recovery for TB, and future airborne pandemic preparedness.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.04.24303743v1" target="_blank">The Global Impact of COVID-19 on Tuberculosis: A Thematic Scoping Review, 2020-2023</a>
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<li><strong>Stress vulnerability and resilience in children facing COVID-19-related discrimination: a quasi-experimental study using polygenic, brain, and sociodemographic data</strong> -
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During the pandemic, perceived COVID-19-related discrimination aggravated children9s stress levels. The remaining question is to evaluate the individual variability in these effects and to identify vulnerable or resilient populations and why. Using the Adolescent Brain and Cognitive Development dataset (<i>N</i> = 1,116) and causal machine learning approach - Generalized Random Forest, we examined the average and individual treatment effects of perceived discrimination on stress levels immediately and six months later. Their variability and key factors were also assessed. We observed significant variability in the acute effects of perceived discrimination across children and pinpointed the frontotemporal cortical volume and white matter connectivity (streamline counts) as key factors of stress resilience and vulnerability. The variability of these neurostructural factors partially originated from the environmental and genetic attributes. The finding was replicated in held-out samples (<i>N</i> = 2,503). Our study has the potential for personalized prescriptive modeling to prevent children9s future psychopathology after the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.04.24303643v1" target="_blank">Stress vulnerability and resilience in children facing COVID-19-related discrimination: a quasi-experimental study using polygenic, brain, and sociodemographic data</a>
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<li><strong>Cause-Specific Excess Mortality in the US During the COVID-19 Pandemic</strong> -
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The COVID-19 pandemic was a significant shock to United States mortality, and it is important to understand how the pandemic impacted other causes of death. We estimated monthly excess mortality in the US by cause of death, age, and sex, for official deaths at ages 15 and older. Data come from the CDC Wonder Multiple Cause of Death database. We used a compositionally robust Generalized Additive Model (GAM) to estimate expected mortality counts in March 2020-December 2022 for eight causes of death: accidents, cardiovascular diseases, cancer, diabetes, influenza and pneumonia, substance-related (drugs and alcohol), suicide, and residual (including COVID-19 related deaths). Analyses were stratified by sex and 15-year age groups from 15-29 to 75+. Excess mortality was calculated as observed deaths minus expected deaths. From March 2020 to December 2022, we estimated 1 298 763 total excess deaths (95% CI: 1 226 542 to 1 370 804). While there were fewer deaths than expected due to some causes like flu/pneumonia and suicide, the largest number of excess deaths, excluding COVID-19, were attributed to cardiovascular diseases (115 765 deaths, 95% CI: 98 697 to 133 783) and substance use (86 637 deaths, 95% CI: 79 273 to 93 690). Percent excess substance-related mortality was high across all ages, while percent excess from cardiovascular diseases was highest at midlife ages. Some of these excess cardiovascular deaths were likely due to undercounted COVID-19 deaths, but others may reflect indirect impacts of the pandemic on healthcare utilization or longer-term effects of COVID-19 infections.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.05.24303783v1" target="_blank">Cause-Specific Excess Mortality in the US During the COVID-19 Pandemic</a>
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<li><strong>Learning from the COVID-19 pandemic: a systematic review of mathematical vaccine prioritization models</strong> -
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As the world becomes ever more connected, the chance of pandemics increases as well. The recent COVID-19 pandemic and the concurrent global mass vaccine roll-out provides an ideal setting to learn from and refine our understanding of infectious disease models for better future preparedness. In this review, we systematically analyze and categorize mathematical models that have been developed to design optimal vaccine prioritization strategies of an initially limited vaccine. As older individuals are disproportionately affected by COVID-19, the focus is on models that take age explicitly into account. The lower mobility and activity level of older individuals gives rise to non-trivial trade-offs. Secondary research questions concern the optimal time interval between vaccine doses and spatial vaccine distribution. This review showcases the effect of various modeling assumptions on model outcomes. A solid understanding of these relationships yields better infectious disease models and thus public health decisions during the next pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.04.24303726v1" target="_blank">Learning from the COVID-19 pandemic: a systematic review of mathematical vaccine prioritization models</a>
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<li><strong>Mental illness and COVID-19 vaccination: a multinational investigation of observational & register-based data</strong> -
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Background: Individuals with mental illness are at higher risk of severe COVID-19 outcomes. However, previous studies on the uptake of COVID-19 vaccination in this population have reported conflicting results. Therefore, we aimed to investigate the association between mental illness and COVID-19 vaccination uptake, using data from five countries. Methods: Data from seven cohort studies (N=325,298), and the Swedish registers (8,080,234), were used to identify mental illness and COVID-19 vaccination uptake. Multivariable modified Poisson regression models were conducted to calculate the prevalence ratio (PR) and 95% CIs of vaccination uptake among individuals with v.s. without mental illness. Results from the cohort studies were pooled using random effects meta-analyses. Findings: Most of the meta-analyses performed using the COVIDMENT study population showed no significant association between mental illness and vaccination uptake. In the Swedish register study population, we observed a very small reduction in the uptake of both the first (prevalence ratio [PR]: 0.98, 95% CI: 0.98-0.99, p<0.001) and second dose among individuals with mental illness; the reduction was however greater among those not using pyschiatric medication (PR: 0.91, 95% CI: 0.91-0.91, p<0.001). Conclusions: The high uptake of COVID-19 vaccination observed among individuals with most types of mental illness highlights the comprehensiveness of the vaccination campaign , however lower levels of vaccination uptake among subgroups of individuals with unmedicated mental illness warrants attention in future vaccination campaigns.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.05.24303691v1" target="_blank">Mental illness and COVID-19 vaccination: a multinational investigation of observational &amp; register-based data</a>
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<li><strong>XBB.1.5 mRNA COVID-19 Vaccination and Inpatient or Emergency Department Visits Among Adults Infected with SARS-CoV-2 JN.1 and XBB-Lineage Variants</strong> -
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Within a multi-state viral genomic surveillance program, we conducted a case-control analysis comparing prior receipt of XBB.1.5-adapted mRNA vaccination between SARS-CoV-2-infected adults with inpatient/ED visits (proxy for severe illness) vs outpatient visits. Among 6,551 patients from September 2023-January 2024, 6.1% with inpatient/ED visits vs 12.0% with outpatient visits had received XBB.1.5 vaccination (aOR=0.41; 95% CI: 0.32-0.53). This protective association was weaker among JN.1 (aOR=0.62; 95% CI: 0.40-0.96) vs XBB-lineage (aOR=0.28; 95% CI: 0.18-0.43) variant infections (interaction, p=0.003). XBB.1.5 vaccination was also protective specifically compared to BA.4/BA.5-adapted mRNA vaccination (aOR=0.60; 95% CI: 0.45-0.79). XBB.1.5 vaccines protect against severe illness, but protection may be weaker against JN.1 vs XBB-lineage variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.05.24303796v1" target="_blank">XBB.1.5 mRNA COVID-19 Vaccination and Inpatient or Emergency Department Visits Among Adults Infected with SARS-CoV-2 JN.1 and XBB-Lineage Variants</a>
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<li><strong>Amino acid profiling of COVID-19 patients blood serum</strong> -
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Main objectives of this study were to analyse metabolomic profile features of patients with COVID-19 using mass spectrometry techniques while taking into account the clinical and laboratory history, and to study the relationship between the severity of COVID-19 symptoms and the concentration of primary metabolites, primarily amino acids. We used frozen blood serum samples of 935 COVID-19 patients from the City Hospital No. 40 biobank collection. Metabolomic profile was studied by HPLS-MS/MS method. R programming language was used for statistical data processing. The difference of metabolic profile of patients with COVID-19 depending on the severity of the disease was revealed based on the performed analysis - for 52 out of 84 detected compounds there were differences with reliability p<0,01. Statistically significant differences in concentration were recorded for organic acids, amino acids and their derivatives. Using samples from the biobank collection, a metabolomic study of the biomaterial of patients hospitalised with the diagnosis of COVID-19 was carried out. According to the results obtained, kynurenine, phenylalanine and acetylcarnitine were associated with the severity of COVID-19 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.05.24303773v1" target="_blank">Amino acid profiling of COVID-19 patients blood serum</a>
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<li><strong>Yeast-based production platform for potent and stable heavy chain-only antibodies</strong> -
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Monoclonal antibodies are the leading drug of the biopharmaceutical market because of their high specificity and tolerability, but the current CHO-based manufacturing platform remains expensive and time-consuming leading to limited accessibility, especially in the case of diseases with high incidence and pandemics. Therefore, there is an urgent need for an alternative production system. In this study, we present a rapid and cost-effective microbial platform for heavy chain-only antibodies (VHH-Fc) in the methylotrophic yeast Komagataella phaffii (aka Pichia pastoris). We demonstrate the potential of this platform using a simplified single-gene VHH-Fc fusion construct instead of the conventional monoclonal antibody format, as this is more easily expressed in Pichia pastoris. We demonstrate that the Pichia-produced VHH-Fc fusion construct is stable and that a Pichia-produced VHH-Fc directed against the SARS-CoV-2 spike has potent SARS-CoV-2 neutralizing activity in vitro and in vivo. We expect that this platform will pave the way towards faster and cheaper development and production of broadly neutralizing single-chain antibodies in yeast.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.04.580093v1" target="_blank">Yeast-based production platform for potent and stable heavy chain-only antibodies</a>
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<li><strong>Filopodial Mechanotransduction is regulated by Angiotensin-Converting Enzyme 2 (ACE2) and by SARS-CoV-2 spike protein</strong> -
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Filopodia are dynamic, actin-rich cellular protrusions, increasingly linked to cellular mechanotransduction. However, how dynamic filopodia translate external mechanical cues remains poorly understood. Recent studies show that the SARS-CoV-2 spike (S) protein binds the ACE2 receptor on airway multicilia and that cilia are required for viral infection(1) and sufficient to induce filopodial extension and viral binding. To test if spike protein is sufficient to induce filopodial expansion, we employed live-cell single-particle tracking with quantum dots targeting ACE2, to reveal a robust filopodia extension and virus binding mechanism requiring the enzymatic activity of ACE2. Using time-lapse imaging, we reveal that spike protein binding to filopodia is associated with intracellular actin remodeling, alterations in bulk cell stiffness, and an elevation in intracellular calcium levels linked to actin-rearrangement, filopodia initiation, and persistence. We propose the activation of ACE2 creates an active signaling and mechanosensory environment within adherent cells and airway epithelial cells that allows the remodeling of actin in filopodia to trap virus and potentially organize viral exit from cells.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.01.581813v1" target="_blank">Filopodial Mechanotransduction is regulated by Angiotensin-Converting Enzyme 2 (ACE2) and by SARS-CoV-2 spike protein</a>
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<li><strong>Why is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study of the free enzyme and its complex with inhibitor 13b-K</strong> -
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During the continuing evolution of SARS-CoV-2, the Omicron variant of concern emerged in the second half of 2021 and has been dominant since November that year. Along with its sublineages, it has maintained a prominent role ever since. The Nsp5 main protease (Mpro) of the Omicron virus is characterized by a single dominant mutation, P132H. Here we determined the X-ray crystal structures of the P132H mutant (or O-Mpro) as free enzyme and in complex with the Mpro inhibitor, the alpha-ketoamide 13b-K, and we conducted enzymology, biophysical as well as theoretical studies to characterize the O-Mpro. We found that O-Mpro has a similar overall structure and binding with 13b-K; however, it displays lower enzymatic activity and lower thermal stability compared to the WT-Mpro (with "WT" referring to the original Wuhan-1 strain). Intriguingly, the imidazole ring of His132 and the carboxylate plane of Glu240 are in a stacked configuration in the X-ray structures determined here. The empirical folding free energy calculations suggest that the O-Mpro dimer is destabilized relative to the WT-Mpro due to the less favorable van der Waals interactions and backbone conformation in the individual protomers. The all-atom continuous constant pH molecular dynamics (MD) simulations reveal that His132 and Glu240 display coupled titration. At pH 7, His132 is predominantly neutral and in a stacked configuration with respect to Glu240 which is charged. In order to examine whether the Omicron mutation eases the emergence of further Mpro mutations, we also determined crystal structures of the relatively frequent P132H+T169S double mutant but found little evidence for a correlation between the two sites.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.04.583178v1" target="_blank">Why is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study of the free enzyme and its complex with inhibitor 13b-K</a>
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<li><strong>A 10-valent composite mRNA vaccine against both influenza and COVID-19</strong> -
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The COVID-19 pandemic caused by SARS-CoV-2 viruses has had a persistent and significant impact on global public health for four years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.05.583547v1" target="_blank">A 10-valent composite mRNA vaccine against both influenza and COVID-19</a>
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</div></li>
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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>An E-health Psychoeducation for People With Bipolar Disorders</strong> - <b>Conditions</b>: Bipolar Disorder; Psychoeducation; COVID-19 Pandemic <br/><b>Interventions</b>: Other: e-health psychoeducation <br/><b>Sponsors</b>: University of Cagliari; Alessandra Perra <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>Sulfureous Water Therapy in Viral Respiratory Diseases</strong> - <b>Conditions</b>: Long-COVID; Post COVID-19 Condition; Chronic COVID-19 Syndrome; Post Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Inhalation of Sulfurous Thermal Water; Other: Inhalation of Sterile Distilled non-pyrogenic Water <br/><b>Sponsors</b>: University of Roma La Sapienza; Università degli studi di Roma Foro Italico; Queen Mary University of London; Bios Prevention Srl <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>Phase 3 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection <br/><b>Sponsors</b>: Novavax <br/><b>Not yet recruiting</b></p></li>
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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>Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection.</strong> - <b>Conditions</b>: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection <br/><b>Interventions</b>: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo) <br/><b>Sponsors</b>: Sheng-Teng Huang <br/><b>Completed</b></p></li>
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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>SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets <br/><b>Sponsors</b>: JKT Biopharma Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
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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>INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo <br/><b>Sponsors</b>: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited <br/><b>Not yet recruiting</b></p></li>
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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 the Safety & Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: IMNN-101 <br/><b>Sponsors</b>: Imunon <br/><b>Not yet recruiting</b></p></li>
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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>Effectiveness of a Nasal Spray on Viral Respiratory Infections</strong> - <b>Conditions</b>: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold <br/><b>Interventions</b>: Device: Nasal Spray HSV Treatment <br/><b>Sponsors</b>: CEN Biotech; Urgo Research, Innovation & Development <br/><b>Recruiting</b></p></li>
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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>GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: GS-441524; Drug: Placebo <br/><b>Sponsors</b>: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc <br/><b>Not yet recruiting</b></p></li>
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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>UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Active, not recruiting</b></p></li>
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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 Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 <br/><b>Interventions</b>: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) <br/><b>Sponsors</b>: Selda Sarıkaya; Zonguldak Bulent Ecevit University <br/><b>Completed</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural products as a source of Coronavirus entry inhibitors</strong> - The COVID-19 pandemic has had a significant and lasting impact on the world. Four years on, despite the existence of effective vaccines, the continuous emergence of new SARS-CoV-2 variants remains a challenge for long-term immunity. Additionally, there remain few purpose-built antivirals to protect individuals at risk of severe disease in the event of future coronavirus outbreaks. A promising mechanism of action for novel coronavirus antivirals is the inhibition of viral entry. To facilitate…</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>Antigenic drift and immunity gap explain reduction in protective responses against influenza A(H1N1)pdm09 and A(H3N2) viruses during the COVID-19 pandemic: a cross-sectional study of human sera collected in 2019, 2021, 2022, and 2023</strong> - CONCLUSION: The observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be…</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>Glycan-directed SARS-CoV-2 inhibition by leek extract and lectins with insights into the mode-of-action of Concanavalin A</strong> - Four years after its outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global challenge for human health. At its surface, SARS-CoV-2 features numerous extensively glycosylated spike proteins. This glycan coat supports virion docking and entry into host cells and at the same time renders the virus less susceptible to neutralizing antibodies. Given the high genetic plasticity of SARS-CoV-2 and the rapid emergence of immune escape variants, targeting the glycan shield…</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>Structural Relationships to Efficacy for Prazole-Derived Antivirals</strong> - Here, an in vitro characterization of a family of prazole derivatives that covalently bind to the C73 site on Tsg101 and assay their ability to inhibit viral particle production is presented. Structurally, increased steric bulk on the 4-pyridyl of the prazole expands the prazole site on the UEV domain toward the β-hairpin in the Ub-binding site and is coupled to increased inhibition of virus-like particle production in HIV-1. Increased bulk also increased toxicity, which is alleviated by…</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>BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir</strong> - Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC(50) = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe…</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 PKA-CREB1 axis regulates coronavirus proliferation by viral helicase nsp13 association</strong> - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) 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>Empowering SARS-CoV-2 variant neutralization with a bifunctional antibody engineered with tandem heptad repeat 2 peptides</strong> - With the global pandemic and the continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the need for effective and broadly neutralizing treatments has become increasingly urgent. This study introduces a novel strategy that targets two aspects simultaneously, using bifunctional antibodies to inhibit both the attachment of SARS-CoV-2 to host cell membranes and viral fusion. We developed pioneering IgG4-(HR2)(4) bifunctional antibodies by creating immunoglobulin…</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>In Silico Evaluation of NO-Sartans against SARS-CoV-2</strong> - CONCLUSION: Based on our in silico studies, CLC-1280 (a Valsartan dinitrate) has the potential to be considered as an inhibitor of the SARS-CoV-2 virus. However, further in vitro and in vivo evaluations are necessary for the drug development process.</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>Immunomodulatory and anticytokine therapeutic potential of three Indian spices constituents and its hyaluronic acid conjugates for prevention and post COVID-19 complications: a computational modeling approach</strong> - Targeted drug delivery to SARS-CoV-2 host target proteins for preventing or blocking COVID-19 infection is making serious concern during COVID-19 pandemic and its consequent waves around the globe. People seek reliable, effective folkloric preventive medication for immediate and precautionary relief from COVID-19. These folkloric medicines were effective and saved many patients during the past COVID-19 pandemic. The current research study aims to deliver antiviral Indian spices phytocompounds…</p></li>
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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>Altered DNA methylation underlies monocyte dysregulation and immune exhaustion memory in sepsis</strong> - Monocytes can develop an exhausted memory state characterized by reduced differentiation, pathogenic inflammation, and immune suppression that drives immune dysregulation during sepsis. Chromatin alterations, notably via histone modifications, underlie innate immune memory, but the contribution of DNA methylation remains poorly understood. Using an ex vivo sepsis model, we show altered DNA methylation throughout the genome of exhausted monocytes, including genes implicated in immune…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting SIRT1 by Scopoletin to Inhibit XBB.1.5 COVID-19 Life Cycle</strong> - Natural products have historically driven pharmaceutical discovery, but their reliance has diminished with synthetic drugs. Approximately 35% of medicines originate from natural products. Scopoletin, a natural coumarin compound found in herbs, exhibits antioxidant, hepatoprotective, antiviral, and antimicrobial properties through diverse intracellular signaling mechanisms. Furthermore, it also enhances the activity of antioxidants. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)…</p></li>
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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>What kind of a problem is loneliness? Representations of connectedness and participation from a study of telepresence technologies in the UK</strong> - Loneliness is represented in UK policy as a public health problem with consequences in terms of individual suffering, population burden and service use. However, loneliness is historically and culturally produced; manifestations of loneliness and social isolation also require social and cultural analysis. We explored meanings of loneliness and social isolation in the UK 2020-2022 and considered what the solutions of telepresence technologies reveal about the problems they are used to address….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Integrated Metabolomic and transcriptomic analyses reveal deoxycholic acid promotes transmissible gastroenteritis virus infection by inhibiting phosphorylation of NF-kappaB and STAT3</strong> - CONCLUSIONS: We identified a significant metabolite, DCA, related to TGEV replication. It added TGEV replication in host cells by inhibiting phosphorylation of NF-κB and STAT3. This study provided novel insights into the metabolomic and transcriptomic alterations related to TGEV infection and revealed potential molecular and metabolic targets for the regulation of TGEV infection.</p></li>
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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>Therapeutic role of miR-19a/b protection from influenza virus infection in patients with coronary heart disease</strong> - Patients with pre-existing medical conditions are at a heightened risk of contracting severe acute respiratory syndrome (SARS), SARS-CoV-2, and influenza viruses, which can result in more severe disease progression and increased mortality rates. Nevertheless, the molecular mechanism behind this phenomenon remained largely unidentified. Here, we found that microRNA-19a/b (miR-19a/b), which is a constituent of the miR-17-92 cluster, exhibits reduced expression levels in patients with coronary…</p></li>
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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>Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention</strong> - The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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