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<title>26 February, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The COVID-19 pandemic era impact on the incidence of the custodial death, due to illness in 36 states and union territories of India-A comparison study (2017–2022)</strong> -
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Abstract: Mahatma Gandhi said that “crime is due to diseased mind and jail should have an environment like hospitals for prisoner’s treatment and care”. A lot of research is carried out globally during COVID-19, on the well being of peoples staying outside the prisons, but very few large scale researches are available to know about the well being of the prisoners during COVID-19 era. The data is provided by the Prison Section of all the 36 States/UTs in prearranged Performa of the NCRB, through an application made by NCRB. A total of 11,289 custodial death occurred among the prisoners residing in various prisons of India, during the study period, out of which 9,406 (83.32 percent, Total-9406 (Obs-216, Mean-43.55, Std. Dev.- 68.87, Min-0, Max-401, Std. Err.- 4.69, 95% Conf. Interval of mean-34.31 -52.78) mortalities were attributed due to illness. Compared to year 2020, our study revealed that the COVID-19 year 2021 has attributed to largest (16.47 percent increased illness custodial death and 12.14 percent increased total mortalities) number of custodial death due to illness. The study revealed that during the study period, majority of the mortalities were due to heart diseases in prisoners (27.28 percent, Total-2566 (Obs-216, Mean-11.88, Std. Dev.- 19.30, Min-0, Max-123, Std. Err.- 1.31, 95% Conf. Interval of mean-9.29 -14.47). Cholera / Diarrhoea attributed to the least number of mortalities during the study period (0.21 percent, Total-20 (Obs-216, Mean-0.09, Std. Dev. - 0.40, Min-0, Max-4, Std. Err. - 0.03, 95% Conf. Interval of mean-.04 -.15). This six years of study revealed that most of the custodial death (42%), due to illness in prisoners of India was due to CVDs and pulmonary diseases. This study also revealed that 27% of custodial deaths due to illness were not clearly categorized. Honourable Justice Lokur, of Supreme Court of India, said in a landmark judgment, in 2013, that “The distinction made by the NCRB [National Crime Records Bureau] between natural and unnatural custodial deaths is not clear. For example, if a prisoner dies due to a lack of proper medical attention or timely medical attention, would that be classified as a natural custodial death or an unnatural custodial death?” The policymakers and decision-makers must think on the necessity of developing Prisoners care policies following the COVID-19 pandemic, in light of the findings of this research study.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/6hncz/" target="_blank">The COVID-19 pandemic era impact on the incidence of the custodial death, due to illness in 36 states and union territories of India-A comparison study (2017–2022)</a>
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</div></li>
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<li><strong>Who has the flu? Early winter 2023-24 spread of flu and COVID-19</strong> -
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<div>
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Winter 2023-24 has seen an unusual confluence of a variety of respiratory illnesses, ranging from flu to RSV (Respiratory Syncytial Virus) and COVID-19. Between December 21, 2023 and January 29, 2024, we surveyed 30,460 individuals aged 18 and older across all 50 states plus the District of Columbia. We asked them if they had experienced an Influenza-like Illness (ILI) defined as experiencing a fever and cough, or a fever and sore throat, and/or if they had been diagnosed with COVID-19, over the previous month. Amongst those who responded yes to such questions, we asked them whether or not they had sought medical attention. In this report, we summarize our findings across a variety of demographic subgroups, including age, race, education, income, gender, and geography.
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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/wfx3g/" target="_blank">Who has the flu? Early winter 2023-24 spread of flu and COVID-19</a>
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</div></li>
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<li><strong>Prognostic factors for mortality, ICU, MIS-C and hospital admission due to SARS-CoV-2 in paediatric patients: A systematic review and meta-analysis</strong> -
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ABSTRACT Background: There is a paucity of data on the factors associated with severe COVID-19 disease, especially in children. This systematic review and meta-analysis aim to identify the risk factors for acute adverse outcomes of COVID-19 within paediatric populations, using the recruitment setting as a proxy of initial disease severity. Methods: A systematic review and meta-analysis were performed representing published evidence from the start of the pandemic up to 14 February 2022. Our primary outcome was the identification of risk factors for adverse outcomes, stratified by recruitment setting (community, hospital). No geographical restrictions were imposed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty in the body of evidence for each meta-analysis. In anticipation of significant clinical and methodological heterogeneity in the meta-analyses, we fitted logistic regression models with random effects. Findings: Our review identified 47 studies involving 94,210 paediatric cases of COVID-19. Infants up to 3 months were more likely to be hospitalised than older children. Gender and ethnicity were not associated with an increased likelihood of adverse outcomes among children within the community setting. Concerning comorbidities, having at least one pre-existing disease increased the odds of hospitalisation. Concerning BMI, underweight children and severely obese were noted to have an increased likelihood of hospital admission. The presence of metabolic disorders and children with underlying cardiovascular diseases, respiratory disorders, neuromuscular disorders and neurologic conditions were also more likely to be hospitalised. Concerning underlying comorbidities, paediatric hospitalised patients with congenital/genetic disease, those obese, with malignancy, cardiovascular diseases and respiratory disease were associated with higher odds of being admitted to ICU or ventilated. Interpretation: Our findings suggest that age, male, gender, and paediatric comorbidities increased the likelihood of hospital and ICU admission. Obesity, malignancy, and respiratory and cardiovascular disorders were among the most important risk factors for hospital and ICU admission among children with COVID-19. The extent to which these factors were linked to actual severity or where the application of cautious preventive care is an area in which further research is needed.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.23.23298451v1" target="_blank">Prognostic factors for mortality, ICU, MIS-C and hospital admission due to SARS-CoV-2 in paediatric patients: A systematic review and meta-analysis</a>
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</div></li>
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<li><strong>Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial</strong> -
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Background Tixagevimab and cilgavimab (AZD7442) are two monoclonal antibodies developed by AstraZeneca for the pre-exposure prophylaxis and treatment of patients infected by SARS-CoV-2. Its effectiveness and safety in patients hospitalized with COVID-19 was not known at the outset of this trial. Methods DisCoVeRy is a phase 3, adaptive, multicentre, randomized, controlled trial conducted in 63 sites in Europe. Participants were randomly assigned (1:1) to receive placebo or tixagevimab-cilgavimab in addition to standard of care. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale. Several clinical, virological, immunological and safety endpoints were also assessed. Findings Due to slow enrolment, recruitment was stopped on July 1st, 2022. The antigen positive modified intention-to-treat population (mITT) was composed of 173 participants randomized to tixagevimab-cilgavimab (n=91) or placebo (n=82), 91.9% (159/173) with supplementary oxygen, and 47.4% (82/173) previously vaccinated at inclusion. There was no significant difference in the distribution of the WHO ordinal scale at day 15 between the two groups (odds ratio (OR) 0.93, 95%CI [0.54-1.61]; p=0.81) nor in any clinical, virological or safety secondary endpoints. In the global mITT (n=226), neutralization antibody titers were significantly higher in the tixagevimab-cilgavimab group/patients compared to placebo at day 3 (Least-square mean differences (LSMD) 1.44, 95% Confidence interval (CI) [1.20-1.68]; p < 10-23) and day 8 (LSMD 0.91, 95%CI [0.64-1.18]; p < 10-8) and it was most important for patients infected with a pre-omicron variant, both at day 3 (LSMD 1.94, 95% CI [1.67-2.20], p < 10-25) and day 8 (LSMD 1.17, 95% CI [0.87-1.47], p < 10-9), with a significant interaction (p < 10-7 and p=0.01 at days 3 and 8, respectively). Interpretation There were no significant differences between tixagevimab-cilgavimab and placebo in clinical endpoints, however the trial lacked power compared to prespecified calculations. Tixagevimab-cilgavimab was well tolerated, with low rates of treatment related events.
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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/10.1101/2024.02.23.24302586v1" target="_blank">Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial</a>
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<li><strong>Global patterns of rebound to normal RSV dynamics following COVID-19 suppression</strong> -
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Introduction Annual epidemics of respiratory synctial virus (RSV) had consistent timing and intensity between seasons prior to the SARS-CoV-2 pandemic (COVID-19). However, starting in April 2020, RSV seasonal activity declined due to COVID-19 non-pharmaceutical interventions (NPIs) before re-emerging after relaxation of NPIs. We described the unusual patterns of RSV epidemics that occurred in multiple subsequent waves following COVID-19 in different countries and explored factors associated with these patterns. Methods Weekly cases of RSV from twenty-eight countries were obtained from the World Health Organisation and combined with data on country-level characteristics and the stringency of the COVID-19 response. Dynamic time warping and regression were used to describe epidemic characteristics, cluster time series patterns, and identify related factors. Results While the first wave of RSV epidemics following pandemic suppression exhibited unusual patterns, the second and third waves more closely resembled typical RSV patterns in many countries. Post-pandemic RSV patterns differed in their intensity and/or timing, with several broad patterns across the countries. The onset and peak timings of the first and second waves of RSV epidemics following COVID-19 suppression were earlier in the Southern Hemisphere. The second wave of RSV epidemics was also earlier with higher population density, and delayed if the intensity of the first wave was higher. More stringent NPIs were associated with lower RSV growth rate and intensity and a shorter gap between the first and second waves. Conclusion Patterns of RSV activity have largely returned to normal following successive waves in the post-pandemic era. Onset and peak timings of future epidemics following disruption of normal RSV dynamics need close monitoring to inform the delivery of preventive and control measures. Keywords: Respiratory synctial virus, epidemic onset, epidemic peak, epidemic rebound, dynamic time warping
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.23.24303265v1" target="_blank">Global patterns of rebound to normal RSV dynamics following COVID-19 suppression</a>
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<li><strong>A Population-Based Cross-Sectional Investigation of COVID-19 Hospitalizations and Mortality Among Autistic People</strong> -
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Background: Current evidence suggests the possibility that autistic people may be at more risk of COVID-19 infection, hospitalisation, and mortality than the general population. Previous studies, however, are either limited in scale or do not investigate potential risk factors. Whilst many risk factors have been speculated to be responsible for severe COVID-19, this research has focused on general population samples. Methods: Using data-linkage and a whole-country population, this study modelled associations between autism and COVID-19 hospitalisation and mortality risk in adults, investigating a multitude of clinical and demographic risk factors. Results: Autistic adults had higher rates of hospitalisation, Standardised Incident Ratio 1.6 in 2020 and 1.3 in 2021, and mortality, Standardised Mortality Ratio 1.52 in 2020 and 1.34 in 2021, due to COVID-19 than the general population. In both populations, age, complex multimorbidity and vaccination status were the most significant predictors of COVID-19 hospitalisation and mortality. Effects of psychotropic medication varied by class. Conclusions: Although similar factors exhibited a positive association with heightened risk of severe COVID-19 in both the autistic and general populations, with comparable effect sizes, mortality rates were elevated among the autistic population as compared to the general population. Specifically, the presence of complex multimorbidity and classification of prescribed medications may emerge as particularly significant predictors of severe COVID-19 among individuals within the autistic population due to higher prevalence of complex multimorbidity in the autistic population and variability in the association between medication classes and severe COVID-19 between both populations, though further research is needed.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.23.24303274v1" target="_blank">A Population-Based Cross-Sectional Investigation of COVID-19 Hospitalizations and Mortality Among Autistic People</a>
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</div></li>
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<li><strong>Changes in opioid prescribing during the COVID-19 pandemic in England: cohort study of 20 million patients in OpenSAFELY-TPP</strong> -
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Background: The COVID-19 pandemic led to disruptions in healthcare delivery, including postponement of elective procedures and difficulty accessing in-person care, which may have increased the need for strong pharmacological pain relief in some patients. Methods: With NHS England approval, we used routine clinical data from >20 million general practice adult patients in OpenSAFELY-TPP. We used interrupted time series analysis to quantify trends in prevalent and incident opioid prescribing prior to the pandemic (January 2018-February 2020) and changes during the COVID-19 lockdown period (March 2020-March 2021) and recovery period (April 2021-June 2022). We identified how these changes varied in people living in care homes, and by age, sex, deprivation, ethnicity, and geographic region. Results: The median number of people prescribed an opioid per month was 50.9 per 1000 patients prior to the pandemic. We observed little change in overall prescribing after the start of the pandemic, except for a temporary increase in March 2020. There was a 9.8% (95%CI -14.5%, -6.5%) reduction in new opioid prescribing from March 2020, sustained to the end of the study period. Reductions in new prescribing were observed for all demographics except people 80+ years. Among care home residents, in April 2020 new opioid prescribing increased by 112.5% (95%CI 92.2%, 134.9%) and parenteral opioid prescribing increased by 186.3% (95%CI 153.1%, 223.9%). Conclusion: Changes in opioid prescribing during the COVID-19 pandemic were mostly consistent across subgroups with the exception of differences by age and care home residence. Among people in care homes, increases in parenteral opioid prescribing likely reflect use to treat end-of-life COVID-19 symptoms. Further research is needed to understand what is driving the reduction in new opioid prescribing and its relation to changes to health care provision during the pandemic.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.23.24303238v1" target="_blank">Changes in opioid prescribing during the COVID-19 pandemic in England: cohort study of 20 million patients in OpenSAFELY-TPP</a>
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<li><strong>Making a Case for an Autism-Specific Multimorbidity Index: A Comparative Cohort Study</strong> -
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Autistic people experience challenges in healthcare, including disparities in health outcomes and multimorbidity patterns distinct from the general population. This study investigated the efficacy of existing multimorbidity indices in predicting COVID-19 mortality among autistic adults and proposes a bespoke index, the ASD-MI, tailored to their specific health profile. Using data from the CVD-COVID-UK/COVID-IMPACT Consortium, encompassing England9s entire population, we identified 1,027 autistic adults hospitalized for COVID-19, among whom 62 died due to the virus. Employing logistic regression with 5-fold cross-validation, we selected diabetes, coronary heart disease, and thyroid disorders as predictors for the ASD-MI, outperforming the Quan Index, a general population-based measure, with an AUC of 0.872 versus 0.828, respectively. Notably, the ASD-MI exhibited better model fit (pseudo-R2 0.25) compared to the Quan Index (pseudo-R2 0.20). These findings underscore the need for tailored indices in predicting mortality risks among autistic individuals. However, caution is warranted in interpreting results, given the limited understanding of morbidity burden in this population. Further research is needed to refine autism-specific indices and elucidate the complex interplay between long-term conditions and mortality risk, informing targeted interventions to address health disparities in autistic adults. This study highlights the importance of developing healthcare tools tailored to the unique needs of neurodivergent populations to improve health outcomes and reduce disparities.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.23.24303273v1" target="_blank">Making a Case for an Autism-Specific Multimorbidity Index: A Comparative Cohort Study</a>
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<li><strong>Thymidine Phosphorylase Mediates SARS-CoV-2 Spike Protein Enhanced Thrombosis in K18-hACE2TG Mice</strong> -
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COVID-19, caused by SARS-CoV-2, is associated with arterial and venous thrombosis, thereby increasing mortality. SARS-CoV-2 spike protein (SP), a viral envelope structural protein, is implicated in COVID-19-associated thrombosis. However, the underlying mechanisms remain unknown. Thymidine phosphorylase (TYMP), a newly identified prothrombotic protein, is upregulated in the plasma, platelets, and lungs of patients with COVID-19 but its role in COVID-19-associated thrombosis is not defined. In this study, we found that wild-type SARS-CoV-2 SP significantly promoted arterial thrombosis in K18-hACE2TG mice. SP-accelerated thrombosis was attenuated by inhibition or genetic ablation of TYMP. SP increased the expression of TYMP, resulting in the activation of signal transducer and activator of transcription 3 (STAT3) in BEAS-2B cells, a human bronchial epithelial cell line. A siRNA-mediated knockdown of TYMP inhibited SP-enhanced activation of STAT3. Platelets derived from SP-treated K18-hACE2TG mice also showed increased STAT3 activation, which was reduced by TYMP deficiency. Activated STAT3 is known to potentiate glycoprotein VI signaling in platelets. While SP did not influence ADP- or collagen-induced platelet aggregation, it significantly shortened activated partial thromboplastin time and this change was reversed by TYMP knockout. Additionally, platelet factor 4 (PF4) interacts with SP, which also complexes with TYMP. TYMP enhanced the formation of the SP/PF4 complex, which may potentially augment the prothrombotic and procoagulant effects of PF4. We conclude that SP upregulates TYMP expression, and TYMP inhibition or knockout mitigates SP-enhanced thrombosis. These findings indicate that inhibition of TYMP may be a novel therapeutic strategy for COVID-19-associated thrombosis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.23.581661v1" target="_blank">Thymidine Phosphorylase Mediates SARS-CoV-2 Spike Protein Enhanced Thrombosis in K18-hACE2TG Mice</a>
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<li><strong>A specific phosphorylation-dependent conformational switch of SARS-CoV-2 nucleoprotein inhibits RNA binding</strong> -
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The nucleoprotein (N) of SARS-CoV-2 encapsidates the viral genome and is essential for viral function. The central disordered domain comprises a serine-arginine-rich domain (SR) that is hyperphosphorylated in infected cells. This modification is thought to regulate function of N, although mechanistic details remain unknown. We use time-resolved NMR to follow local and long-range structural changes occurring during hyperphosphorylation by the kinases SRPK1/GSK-3/CK1, thereby identifying a conformational switch that abolishes interaction with RNA. When 8 approximately uniformly-distributed sites are phosphorylated, the SR domain competitively binds the same interface as single-stranded RNA, resulting in RNA binding inhibition. Phosphorylation by PKA does not prevent RNA binding, indicating that the pattern resulting from the physiologically-relevant kinases is specific for inhibition. Long-range contacts between the RNA-binding, linker and dimerization domains are also abrogated, phenomena possibly related to genome packaging and unpackaging. This study provides insight into recruitment of specific host kinases to regulate viral function.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.22.579423v1" target="_blank">A specific phosphorylation-dependent conformational switch of SARS-CoV-2 nucleoprotein inhibits RNA binding</a>
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<li><strong>A pan-tissue, pan-disease compendium of human orphan genes</strong> -
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Species-specific genes are ubiquitous in evolution, with functions ranging from prey paralysis to survival in subzero temperatures. Because they are typically expressed under limited conditions and lack canonical features, such genes may be vastly under-identified, even in humans. Here, we leverage terabytes of human RNA-Seq data to identify thousands of highly-expressed transcripts that do not correspond to any Gencode-annotated gene. Many may be novel ncRNAs although 80% of them contain ORFs that have the potential of encoding proteins unique to Homo sapiens (orphan genes). We validate our findings with independent strand-specific and single-cell RNA-seq datasets. Hundreds of these novel transcripts overlap with deleterious genomic variants; thousands show significant association with disease-specific patient survival. Most are dynamically regulated and accumulate selectively in particular tissues, cell-types, developmental stages, tumors, COVID-19, sex, and ancestries. As such, these transcripts hold potential as diagnostic biomarkers or therapeutic targets. To empower future discovery, we provide a compendium of these huge RNA-Seq expression data, and RiboSeq data, with associated metadata. Further, we supply the gene models for the novel genes as UCSC Genome Browser tracks.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.21.581488v1" target="_blank">A pan-tissue, pan-disease compendium of human orphan genes</a>
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<li><strong>Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike</strong> -
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The trimeric spike protein plays an essential role in the SARS-CoV-2 virus lifecycle, facilitating virus entry through binding to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediating viral and host membrane fusion. The SARS-CoV-2 spike contains an allosteric fatty acid (FA) binding site at the interface between two neighbouring receptor-binding domains. This site, also found in some other coronaviruses, binds free fatty acids such as linoleic and oleic acid, and other small molecules. Understanding allostery and how this site modulates the behaviour of different regions in this protein could potentiate the development of promising alternative strategies for new coronavirus therapies. Here, we apply dynamical nonequilibrium molecular dynamics (D-NEMD) simulations to investigate allosteric effects and identify the communication pathways in the fully glycosylated spike in the original SARS-CoV-2 ancestral variant. The results reveal the allosteric networks that connect the FA site to important functional regions of the protein, including some more than 40 Angstroms away. These regions include the receptor binding motif, an antigenic supersite in the N-terminal domain, the furin cleavage site, the regions surrounding the fusion peptide and a second allosteric site known to bind heme and biliverdin. The networks identified here highlight the complexity of the allosteric modulation in this protein and reveal a striking and unexpected connection between different allosteric sites. Notably, 65% of amino acid substitutions, deletions and insertions in the Alpha, Beta, Delta, Gamma and Omicron variants map onto or close to the identified allosteric pathways.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.06.565757v2" target="_blank">Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike</a>
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<li><strong>Thrombotic and thromboembolic events, with or without thrombocytopenia, following viral vector-based COVID-19 vaccines administration: a systematic review protocol</strong> -
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Background Viral vector-based COVID-19 vaccines have proven to be effective and safe in clinical trials and post-authorization studies. Although infrequent, some serious thrombotic and thromboembolic events following immunization have emerged, and causality assessment committees must consider and critically assess different sources of evidence to inform their decisions about whether these events supposedly attributable to vaccination or immunization (ESAVI) are associated with the vaccine or are coincidental. Therefore, this systematic review aims to gather information on the association and biological mechanisms between thrombotic and thromboembolic events, with or without thrombocytopenia, and the administration of viral vector-based COVID-19 vaccines. Methods We will conduct a systematic review following the evidence synthesis framework proposed by the Pan American Health Organization to support the ESAVI causality assessment. We will search for primary clinical and preclinical studies in the Epistemonikos9 COVID-19 L.OVE (Living Overview of the Evidence) repository, a comprehensive and validated source of COVID-19 evidence. We will include studies reporting any thrombotic or thromboembolic event, with or without thrombocytopenia, after the administration of a viral vector-based COVID-19 vaccine. The screening and data extraction will be performed by two independent authors. We will assess the risk of bias by two reviewers using the appropriate tool for each study design. Discrepancies will be discussed or resolved by a third author. We will use GRADE to assess the certainty of evidence for clinical studies and prepare summary of findings tables. For individual-based (case series and case reports) and preclinical studies, we will summarize the results in descriptive tables. Expected results and implications This will be the first systematic review using the evidence synthesis framework for ESAVI causality assessment, currently under validation by the Pan American Health Organization and the Epistemonikos Foundation. By gathering clinical and preclinical evidence, it is expected to inform about the risks of thromboembolic events following vaccination with viral vector-based COVID-19 vaccines, and also the possible underlying biological mechanisms. Policymakers, such as safe vaccination committees, and other evidence synthesis authors could replicate this novel methodology to strengthen the evidence-based ESAVI causality assessment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.22.24303207v1" target="_blank">Thrombotic and thromboembolic events, with or without thrombocytopenia, following viral vector-based COVID-19 vaccines administration: a systematic review protocol</a>
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<li><strong>Prospective study of machine learning for identification of high-risk COVID-19 patients</strong> -
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The Coronavirus Disease 2019 (COVID-19) pandemic constituted a public health crisis with a devastating effect in terms of its death toll and effects on the world economy. Notably, machine learning methods have played a pivotal role in devising novel technological solutions designed to tackle challenges brought forth by this pandemic. In particular, tools for the rapid identification of high-risk COVID-19 patients have been developed to aid in the effective allocation of hospital resources and for containing the spread of the virus. A comprehensive validation of such intelligent technological approaches is needed to ascertain their clinical utility; importantly, it may help develop future strategies for efficient patient classification to be used in future viral outbreaks. Here we present a prospective study to evaluate the performance of state-of-the-art machine-learning models proposed in PloS one 16, e0257234 (2021), which we developed for the identification of high-risk COVID-19 patients across four identified clinical stages. The model relies on artificial neural networks trained with historical patient data from Mexico. To assess their predictive capabilities across the six, registered, epidemiological waves of COVID-19 infection in Mexico, we measure the accuracy within each wave without retraining the neural networks. We then compare their performance against neural networks trained with cumulative historical data up to the end of each wave. Our findings indicate that models trained using early historical data exhibit strong predictive capabilities, which allows us to accurately identify high-risk patients in subsequent epidemiological waves—under clearly varying vaccination, prevalent viral strain, and medical treatment conditions. These results show that artificial intelligence-based methods for patient classification can be robust throughout an extended period characterized by constantly evolving conditions, and represent a potentially powerful tool for tackling future pandemic events, particularly for clinical outcome prediction of individual patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.21.24303159v1" target="_blank">Prospective study of machine learning for identification of high-risk COVID-19 patients</a>
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<li><strong>Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution</strong> -
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High priority efforts are under way to support the development of novel mucosal COVID-19 vaccines, such as the US Government′s Project NextGen and the Center for Epidemic Preparedness Innovations′ (CEPI) goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how the immunogenicity of mucosal vaccines will be evaluated. This study investigated the role of oral mucosal antibody responses in viral clearance and in COVID-19 symptom duration. Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022. High and moderate oral fluid anti-spike (S) SIgA post infection was associated with significantly higher likelihood of viral clearance and of COVID-19 symptom resolution across age groups. Those with high and moderate anti-S SIgA cleared the virus and recovered 14 days (95% CI: 10-18 days) and 9-10 days (95% CI: 6-14 days) earlier, respectively. Delayed but higher oral fluid anti-S IgG was associated with significantly longer time to viral clearance and recovery. The effect size of moderate or high SIgA was equivalent to prior COVID-19 vaccine immunity, which was also associated with faster clearance and recovery. Unvaccinated adults with prolonged COVID-19 symptoms had significantly lower anti-RBD SIgA 15-30 days after infection onset (p<0.001). Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new vaccines that can boost local mucosal immunity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.21.24303146v1" target="_blank">Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt</strong> - <b>Conditions</b>: Mucormycosis; Rhinocerebral (Etiology); COVID-19 <br/><b>Interventions</b>: Procedure: debridment <br/><b>Sponsors</b>: Nasser Institute For Research and Treatment <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>Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 <br/><b>Interventions</b>: Drug: Hyperbaric oxygen <br/><b>Sponsors</b>: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk <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>Mindfulness-based Mobile Applications Program</strong> - <b>Conditions</b>: COVID-19; Cell Phone Use; Nurse; Mental Health <br/><b>Interventions</b>: Device: mindfulness-based mobile applications program <br/><b>Sponsors</b>: Yu-Chien 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>Attention Training for COVID-19 Related Distress</strong> - <b>Conditions</b>: Anxiety <br/><b>Interventions</b>: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training <br/><b>Sponsors</b>: Palo Alto University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Correlation of Antibody Response to COVID-19 Vaccination in Pregnant Woman and Transplacental Passage Into Cord Blood.</strong> - <b>Conditions</b>: Covid-19 <br/><b>Interventions</b>: Diagnostic Test: COVID-19 Spike Protein IgG Quantitative Antibody (CMIA) <br/><b>Sponsors</b>: Vachira Phuket Hospital <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>UNAIR Inactivated COVID-19 Vaccine as Homologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines; COVID-19 Virus Disease <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; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia; Indonesia-MoH <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>Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: CD40.RBDv vaccin (SARS-Cov2 Vaccin) <br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; LinKinVax; Vaccine Research Institute (VRI), France <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>High-definition Transcranial Direct Current Ctimulation and Chlorella Pyrenoidosa to Reduce Cardiovascular Risk</strong> - <b>Conditions</b>: Cardiovascular Diseases; Long Covid19 <br/><b>Interventions</b>: Other: High Definition-transcranial Direct Current Stimulation; Dietary Supplement: Chlorella Pyrenoidosa <br/><b>Sponsors</b>: Federal University of Paraíba; City University of New York <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>SGB for COVID-induced Parosmia</strong> - <b>Conditions</b>: COVID-19-Induced Parosmia <br/><b>Interventions</b>: Drug: Stellate Ganglion Block; Drug: Placebo Sham Injection <br/><b>Sponsors</b>: Washington University School of Medicine <br/><b>Recruiting</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>Efficacy of Host Cell Serine Protease Inhibitor MM3122 against SARS-CoV-2 for Treatment and Prevention of COVID-19</strong> - We have developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases including transmembrane protease serine 2 (TMPRSS2), matriptase and hepsin. TMPRSS2 is a membrane associated protease which is highly expressed in the upper and lower respiratory tract and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell receptor binding, entry, replication, and dissemination of new virion particles. We have…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antimicrobial and Virus Adsorption Properties of Y-Zeolite Exchanged with Silver and Zinc Cations</strong> - The antimicrobial activity of silver and zinc exchanged cations in Y-zeolite (Ag/CBV-600, Zn/CBV-600) is evaluated against Staphylococcus aureus (gram (+)) and Escherichia coli (gram (-)) bacteria along with their adsorption capacity for viruses: brome mosaic virus (BMV), cowpea chlorotic mottle virus (CCMV), and the bacteriophage MS2. The physicochemical properties of synthesized nanomaterials are characterized by inductively coupled plasma optical emission spectroscopy (ICP-OES), UV-Vis…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Diphenyl ethers from the cultured lichen mycobiont of <em>Graphis handelii</em> Zahlbr</strong> - CONCLUSION: A new compound, handelone (1) was isolated from the cultured mycobiont of Graphis handelii. From these compounds, four new derivatives were prepared. Compound 1 showed good activity against M^(pro) with an IC(50) value of 5.2 μM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays.</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>Sialic Acid Conjugate-Modified Cationic Liposomal Paclitaxel for Targeted Therapy of Lung Metastasis in Breast Cancer: What a Difference the Cation Content Makes</strong> - Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these…</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>Raman spectroscopy study of 7,8-dihydrofolate inhibition on the Wuhan strain SARS-CoV-2 binding to human ACE2 receptor</strong> - Emerging evidence suggests that elevated levels of folic acid in the bloodstream may confer protection against Wuhan-SARS-CoV-2 infection and mitigate its associated symptoms. Notably, two comprehensive studies of COVID-19 patients in Israel and UK uncovered a remarkable trend, wherein individuals with heightened folic acid levels exhibited only mild symptoms and necessitated no ventilatory support. In parallel, research has underscored the potential connection between decreased folic acid…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2β1</strong> - Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sulfated Glycans Inhibit the Interaction of MERS-CoV Receptor Binding Domain with Heparin</strong> - Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of host cells is used by many viruses as cofactor to facilitate viral attachment and initiate cellular entry. Therefore, inhibition of the interaction between viruses and HS could be a promising…</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 Potential of Usnic-Acid-Based Thiazolo-Thiophenes as Inhibitors of the Main Protease of SARS-CoV-2 Viruses</strong> - Although the COVID-19 pandemic caused by SARS-CoV-2 viruses is officially over, the search for new effective agents with activity against a wide range of coronaviruses is still an important task for medical chemists and virologists. We synthesized a series of thiazolo-thiophenes based on (+)- and (-)-usnic acid and studied their ability to inhibit the main protease of SARS-CoV-2. Substances containing unsubstituted thiophene groups or methyl- or bromo-substituted thiophene moieties showed…</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>Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells</strong> - Viruses evolve many strategies to ensure the efficient synthesis of their proteins. One such strategy is the inhibition of the integrated stress response-the mechanism through which infected cells arrest translation through the phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α). We have recently shown that the human common cold betacoronavirus OC43 actively inhibits eIF2α phosphorylation in response to sodium arsenite, a potent inducer of oxidative…</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>Feasibility Study of Developing a Saline-Based Antiviral Nanoformulation Containing Lipid-Soluble EGCG: A Potential Nasal Drug to Treat Long COVID</strong> - CONCLUSION: Nanoformulations containing EC16 showed properties compatible with nasal application to rapidly inactivate SARS-CoV-2 residing in the olfactory mucosa and to reduce inflammation in the CNS, pending additional formulation and safety studies.</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>Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning</strong> - SARS-CoV-2 Main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome, which is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development. Herein, we performed a large-scale virtual screening by comparing multiple structural descriptors of reference molecules with reported anti-coronavirus activity against a library with >17 million compounds. Further filtering, performed by applying two machine learning algorithms, identified…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies</strong> - The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection’s spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their…</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>Silver Nanoparticles In Situ Synthesized and Incorporated in Uniaxial and Core-Shell Electrospun Nanofibers to Inhibit Coronavirus</strong> - In the present study, we sought to develop materials applicable to personal and collective protection equipment to mitigate SARS-CoV-2. For this purpose, AgNPs were synthesized and stabilized into electrospinning nanofiber matrices (NMs) consisting of poly(vinyl alcohol) (PVA), chitosan (CHT), and poly-ε-caprolactone (PCL). Uniaxial nanofibers of PVA and PVA/CHT were developed, as well as coaxial nanofibers of PCL[PVA/CHT], in which the PCL works as a shell and the blend as a core. A crucial…</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 Design, Synthesis and Mechanism of Action of Paxlovid, a Protease Inhibitor Drug Combination for the Treatment of COVID-19</strong> - The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an enormous challenge to health care systems and medicine. As a result of global research efforts aimed at preventing and effectively treating SARS-CoV-2 infection, vaccines with fundamentally new mechanisms of action and some small-molecule antiviral drugs targeting key proteins in the viral cycle have been developed. The most effective small-molecule drug approved to date for the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Antiherpesviral Host-Directed Strategy Based on CDK7 Covalently Binding Drugs: Target-Selective, Picomolar-Dose, Cross-Virus Reactivity</strong> - The repertoire of currently available antiviral drugs spans therapeutic applications against a number of important human pathogens distributed worldwide. These include cases of the pandemic severe acute respiratory coronavirus type 2 (SARS-CoV-2 or COVID-19), human immunodeficiency virus type 1 (HIV-1 or AIDS), and the pregnancy- and posttransplant-relevant human cytomegalovirus (HCMV). In almost all cases, approved therapies are based on direct-acting antivirals (DAAs), but their benefit,…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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