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186 lines
48 KiB
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<title>26 February, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Moral dilemmas and trust in leaders during a global health crisis</strong> -
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Trust in leaders is central to citizen compliance with public policies. One potential determinant of trust is how leaders resolve conflicts between utilitarian and non- utilitarian ethical principles in moral dilemmas. Past research suggests that utilitarian responses to dilemmas can both erode and enhance trust in leaders: sacrificing some people to save many others (‘instrumental harm’) reduces trust, while maximizing the welfare of everyone equally (‘impartial beneficence’) may increase trust. In a multi-site experiment spanning 22 countries on six continents, participants (N = 23,929) completed self-report (N = 17,591) and behavioral (N = 12,638) measures of trust in leaders who endorsed utilitarian or non-utilitarian principles in dilemmas concerning the COVID-19 pandemic. Across both the self-report and behavioral measures, endorsement of instrumental harm decreased trust, while endorsement of impartial beneficence increased trust. These results show how support for different ethical principles can impact trust in leaders, and inform effective public communication during times of global crisis.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/mzswb/" target="_blank">Moral dilemmas and trust in leaders during a global health crisis</a>
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<li><strong>Crystal structure and activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain like protease revealed new allosteric sites for antiviral therapies</strong> -
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Emerging variants of SARS-CoV-2 still threaten the effectiveness of currently deployed vaccines, and antivirals can prove to be an effective therapeutic option for attenuating it. The papain-like protease (PLpro) is an attractive target due to its sequence conservation and critical role in the replication and pathogenesis of SARS-CoV-2. PLpro also plays very important role in modulation of host immune responses by deubiquitinating (DUBs) or deISGylating host proteins. Thus, targeting PLpro serves as a two-pronged approach to abate SARS-CoV-2. Due to its structural and functional similarities with the host DUB enzymes, an in-house library of DUB inhibitors was constituted in this study. Five promising compounds exhibiting high binding affinities with the substrate binding site of PLpro were identified from a library of 81 compounds with in silico screening, docking, and simulation studies. Interestingly, lithocholic acid, linagliptin, teneligliptin, and flupenthixol significantly inhibited the proteolytic activity of PLpro. Each of these compounds abrogated in vitro replication of SARS-CoV-2 with EC50 values in the range of 5-21 micro M. In addition, crystal structure of SARS-CoV-2 PLpro and its complex with inhibitors have been determined that revealed their inhibitory mechanism. The findings of this study provide the proof-of-principle that the DUB inhibitors hold high potential as a new class of therapeutics against SARS-CoV-2. Additionally, this is the first study that has opened a new avenue towards not only targeting PLpro active site but also simultaneously directing towards restoration of antiviral immune response of the host for deterring SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.11.516107v2" target="_blank">Crystal structure and activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain like protease revealed new allosteric sites for antiviral therapies</a>
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</div></li>
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<li><strong>Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral</strong> -
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<div>
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Expanding antiviral treatment options against SARS-CoV-2 remains crucial as the virus evolves rapidly and drug resistant strains have emerged. Broad spectrum host-directed antivirals (HDA) are promising therapeutic options, however the robust identification of relevant host factors by CRISPR/Cas9 or RNA interference screens remains challenging due to low consistency in the resulting hits. To address this issue, we employed machine learning based on experimental data from knockout screens and a drug screen. As gold standard, we assembled perturbed genes reducing virus replication or protecting the host cells. The machines based their predictions on features describing cellular localization, protein domains, annotated gene sets from Gene Ontology, gene and protein sequences, and experimental data from proteomics, phospho-proteomics, protein interaction and transcriptomic profiles of SARS-CoV-2 infected cells. The models reached a remarkable performance with a balanced accuracy of 0.82 (knockout based classifier) and 0.71 (drugs screen based classifier), suggesting patterns of intrinsic data consistency. The predicted host dependency factors were enriched in sets of genes particularly coding for development, morphogenesis, and neural related processes. Focusing on development and morphogenesis-associated gene sets, we found {beta}-catenin to be central and selected PRI-724, a canonical {beta}-catenin/CBP disruptor, as a potential HDA. PRI-724 limited infection with SARS-CoV-2 variants, SARS-CoV-1, MERS-CoV and IAV in different cell line models. We detected a concentration-dependent reduction in CPE development, viral RNA replication, and infectious virus production in SARS-CoV-2 and SARS-CoV-1-infected cells. Independent of virus infection, PRI-724 treatment caused cell cycle deregulation which substantiates its potential as a broad spectrum antiviral. Our proposed machine learning concept may support focusing and accelerating the discovery of host dependency factors and the design of antiviral therapies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.23.529833v1" target="_blank">Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral</a>
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</div></li>
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<li><strong>Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution</strong> -
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During the COVID-19 pandemic, human behavior change as a result of nonpharmaceutical interventions such as isolation may have induced directional selection for viral evolution. By combining previously published empirical clinical data analysis and multi-level mathematical modeling, we found that the SARS-CoV-2 variants selected for as the virus evolved from the pre-Alpha to the Delta variant had earlier and higher infectious periods but a shorter duration of infection. Selection for increased transmissibility shapes the viral load dynamics, and the isolation measure is likely to be a driver of these evolutionary transitions. In addition, we showed that a decreased incubation period and an increased proportion of asymptomatic infection were also positively selected for as SARS-CoV-2 mutated to the extent that people did not isolate. We demonstrated that the Omicron variants evolved in these ways to adapt to human behavior. The quantitative information and predictions we present here can guide future responses in the potential arms race between pandemic interventions and viral evolution.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.23.529742v1" target="_blank">Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution</a>
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</div></li>
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<li><strong>Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology</strong> -
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<div>
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Defending against future pandemics may require vaccine platforms that protect across a range of related pathogens. The presentation of multiple receptor-binding domains (RBDs) from evolutionarily-related viruses on a nanoparticle scaffold elicits a strong antibody response to conserved regions. Here we produce quartets of tandemly-linked RBDs from SARS-like betacoronaviruses coupled to the mi3 nanocage through a SpyTag/SpyCatcher spontaneous reaction. These Quartet Nanocages induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented on the vaccine. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increased the strength and breadth of an otherwise narrow immune response. Quartet Nanocages are a strategy with potential to confer heterotypic protection against emergent zoonotic coronavirus pathogens and facilitate proactive pandemic protection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.24.529520v1" target="_blank">Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology</a>
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<li><strong>Real-time forecasting of COVID-19-related hospital strain in France using a non-Markovian mechanistic model</strong> -
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Background The COVID-19 pandemic emphasised the importance of access to reliable real-time forecasts for key epidemiological indicators. Given the strong heterogeneity between regions, providing forecasts at the local level is essential for health professionals. Methods We developed a SARS-CoV-2 transmission model in France, COVIDici, that performs parameter estimation using up-to-date vaccination coverage and hospital data to provide forecasts up to a four-week horizon based on the current epidemic trend. We present the model, its associated online tool and perform a retrospective evaluation of the forecasts provided from January to December 2021 by comparing to three standard statistical forecasting methods (auto-regression, exponential smoothing, and ARIMA) at the national and regional levels. Results COVIDici allowed simultaneous real-time visualisation of several indicators of the COVID-19 epidemic at the sub-national level. For anticipating risk of critical care unit overload, it performed worse compared to the baseline methods for forecasts under the three-week horizon, but had better point forecasts at the longest horizons (e.g. four weeks) for 8 of the 13 regions considered depending on the metric. Conclusions Effective communication between modelers and clinicians is essential for utilising forecasts for health care planning. Online visualisation tools and consideration of how metrics can be affected by distortion from non-pharmaceutical government interventions facilitate this dialogue.
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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/10.1101/2023.02.21.23286228v1" target="_blank">Real-time forecasting of COVID-19-related hospital strain in France using a non-Markovian mechanistic model</a>
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</div></li>
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<li><strong>Performance of Rapid Antigen Tests Based on Symptom Onset and Close Contact Exposure: A secondary analysis from the Test Us At Home prospective cohort study</strong> -
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Abstract Background: The performance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) in temporal relation to symptom onset or exposure is unknown, as is the impact of vaccination on this relationship. Objective: To evaluate the performance of Ag-RDT compared with RT-PCR based on day after symptom onset or exposure in order to decide on when to test. Design, Setting, and Participants: The Test Us at Home study was a longitudinal cohort study that enrolled participants over 2 years old across the United States between October 18, 2021 and February 4, 2022. All participants were asked to conduct Ag-RDT and RT-PCR testing every 48 hours over a 15-day period. Participants with one or more symptoms during the study period were included in the Day Post Symptom Onset (DPSO) analyses, while those who reported a COVID-19 exposure were included in the Day Post Exposure (DPE) analysis. Exposure: Participants were asked to self-report any symptoms or known exposures to SARS-CoV-2 every 48-hours, immediately prior to conducting Ag-RDT and RT-PCR testing. The first day a participant reported one or more symptoms was termed DPSO 0, and the day of exposure was DPE 0. Vaccination status was self-reported. Main Outcome and Measures: Results of Ag-RDT were self-reported (positive, negative, or invalid) and RT-PCR results were analyzed by a central laboratory. Percent positivity of SARS-CoV-2 and sensitivity of Ag-RDT and RT-PCR by DPSO and DPE were stratified by vaccination status and calculated with 95% confidence intervals. Results: A total of 7,361 participants enrolled in the study. Among them, 2,086 (28.3%) and 546 (7.4%) participants were eligible for the DPSO and DPE analyses, respectively. Unvaccinated participants were nearly twice as likely to test positive for SARS-CoV-2 than vaccinated participants in event of symptoms (PCR+: 27.6% vs 10.1%) or exposure (PCR+: 43.8% vs. 22.2%). The highest proportion of vaccinated and unvaccinated individuals tested positive on DPSO 2 and DPE 5-8. Performance of RT-PCR and Ag-RDT did not differ by vaccination status. Ag-RDT detected 78.0% (95% Confidence Interval: 72.56-82.61) of PCR-confirmed infections by DPSO 4. For exposed participants, Ag-RDT detected 84.9% (95% CI: 75.0-91.4) of PCR-confirmed infections by day five post-exposure (DPE 5). Conclusions and Relevance: Performance of Ag-RDT and RT-PCR was highest on DPSO 0-2 and DPE 5 and did not differ by vaccination status. These data suggests that serial testing remains integral to enhancing the performance of Ag-RDT.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.21.23286239v1" target="_blank">Performance of Rapid Antigen Tests Based on Symptom Onset and Close Contact Exposure: A secondary analysis from the Test Us At Home prospective cohort study</a>
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<li><strong>COVID-19 preventive measures in Rohingya refugee camps: An assessment of knowledge, attitude and practice toward COVID-19</strong> -
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Background: Although many studies were conducted on COVID-19 knowledge, attitude, and practice among the general population in many countries, very little is known about refugees, particularly Rohingya refugees in Cox9s Bazar. A vast array of Risk Communication and Community Engagement (RCCE) interventions were implemented in Cox’s Bazar with the intent of reducing disease transmission by empowering the community to adopt public health measures. Objectives: The study aimed to evaluate the current state of knowledge, attitude, and practice among Rohingya refugees as a result of RCCE initiatives. Materials and Methods: A cross-sectional study was conducted with 500 Rohingya individuals. Participants in the study were Rohingya refugees residing in five randomly selected camps where IOM health was operating. Using a structured questionnaire, skilled community health workers surveyed the Rohingya population. In addition to the survey on knowledge, attitude, and practice, the study gathered information on the perspectives and relevance of sociodemographic factors that influence KAP. Results: The study findings indicate that the mean scores for knowledge, attitude, and practice were 9.93 (out of 14), 7.55 (out of 11), and 2.71 (out of 7) respectively. Association was found between knowledge and practice level and age group – elderly age group (>/= 61 years) had less level of knowledge (AOR 0.42, P value= 0.05) and the late mid age group (46 – 60 years) had better practice level (AOR 2.67, P value <0.001). A significant association was also found between good knowledge level and medium family size (5 – 6 members) (P value= 0.02). Conclusions: The study reveals that the Cox9s Bazar Rohingya refugee community has a low knowledge and attitude score about COVID-19 prevention measures. Especially the KAP scores were found significantly low in elderly population. Despite RCCE interventions, the practice level of these measures exhibited a considerably low score. Poor implementation of preventive measures must be identified and remedied, involving the community in future outbreaks of a similar nature.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.21.23286227v1" target="_blank">COVID-19 preventive measures in Rohingya refugee camps: An assessment of knowledge, attitude and practice toward COVID-19</a>
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<li><strong>Genomic surveillance reveals early detection and transition of Delta to Omicron Lineages of SARS-CoV-2 Variants in wastewater treatment plants of Pune, India</strong> -
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The COVID-19 pandemic has emphasized the urgency for rapid public health surveillance methods in early detection and monitoring of the transmission of infectious diseases. The wastewater-based epidemiology (WBE) has emerged as a promising tool to analyze and enumerate the prevalence of infectious pathogens in a population ahead of time. In the present study, real time quantitative polymerase chain reaction (RT-qPCR) and Illumina sequencing was performed to determine the SARS-CoV-2 load trend and dynamics of variants over a longitudinal scale in 442 wastewater (WW) samples collected from 10 sewage treatment plants (STPs) of Pune city, India, during November 2021 to April-2022. In total 426 distinct lineages representing 17 highly transmissible variants of SARS-CoV-2 were identified. The SARS-CoV-2 Omicron variant fragments were detected in WW samples prior to its detection in clinical cases. Moreover, highly contagious sub-lineages of Omicron, such as BA.2.12 (0.8-0.25%), BA.2.38 (0.8-1.0%), BA.2.75 (0.01-0.02%), BA.3 (0.09-6.3%), BA.4 (0.24-0.29%), and XBB (0.01-13.7%) fragments were significantly detected. The longitudinal analysis also suggested the presence of the BA.5 lineage in November 2021, which was not reported in the clinical settings throughout the duration of this study, indicative of silent variant persistence. Overall, the present study demonstrated the practicality of WBE in early detection of SARS CoV-2 variants, which could be useful in tracking future outbreaks of SARS-CoV-2. Such approaches could be implicated in the monitoring of the infectious agents before they appear in clinical cases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.21.23286222v1" target="_blank">Genomic surveillance reveals early detection and transition of Delta to Omicron Lineages of SARS-CoV-2 Variants in wastewater treatment plants of Pune, India</a>
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<li><strong>Pathways to altered virulence of SARS-CoV-2</strong> -
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The recently emerged SARS-CoV-2 virus has led to a prolonged pandemic characterized by ongoing viral evolution. Vaccines have been an important piece in the strategy to combat the virus but have been insufficient to contain it as the virus continues to evolve to evade immunity developed by vaccination and infection. A consistent argument is that vaccination or prior immunity will lead to less severe infections. In this review, we address the question of whether the virus can evolve to become more virulent, despite prior infection. We describe the intrinsic characteristics of the virus and their relationship to altered virulence. We show that it is likely that viral evolution is subject to evolutionary drift, and it cannot be assumed that the virus will necessarily evolve to be less virulent, or that prior immunity will offer durable protection against severe disease. This has strong implications for public health strategies to confront the ongoing challenges presented by SARS-CoV-2 and implies that there are significant risks to a strategy based on the assumption of waning virulence.
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🖺 Full Text HTML: <a href="https://osf.io/k4hb3/" target="_blank">Pathways to altered virulence of SARS-CoV-2</a>
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<li><strong>Integrating autoethnography and dynamic p-technique: A convergent explanatory bidirectional single-subject study on embodying mindfulness as an instructor</strong> -
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This article contributes to the mixed methods research (MMR) field a description of utilizing MMR in a single-subject design. The example utilizes a convergent intensive longitudinal data collection strategy and an explanatory bidirectional framework for data merging analysis to examine one female faculty member’s practices of incorporating social-emotional learning (SEL) and mindfulness during the COVID-19 pandemic to reduce burnout. By examining results from the dynamic p-technique (a special case of structural equation modeling) and reflexive journaling resulting in autoethnography, a clearer, longitudinal picture of one faculty member’s lived experience emerged. The study is a concrete demonstration of how structural equation modeling and autoethnography methods can be combined within a convergent data collection strategy and explanatory bidirectional analytic framework. Readers interested in replicating the dynamic p-technique analyses can access our tutorial and supplemental materials at https://bit.ly/osfburnout.
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🖺 Full Text HTML: <a href="https://osf.io/4jhgb/" target="_blank">Integrating autoethnography and dynamic p-technique: A convergent explanatory bidirectional single-subject study on embodying mindfulness as an instructor</a>
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<li><strong>Durable reprogramming of neutralising antibody responses following breakthrough Omicron infection</strong> -
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SARS-CoV-2 breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months post-infection. Both BA.1 and BA.2 infection robustly boosted neutralisation activity against the infecting strain while expanding breadth against other Omicron strains. Cross-reactive memory B cells against both ancestral and Omicron spike were predominantly expanded by infection, with limited recruitment of de novo Omicron-specific B cells or antibodies. Modelling of neutralisation titres predicts that protection from symptomatic reinfection against antigenically similar strains will be remarkably durable, but is undermined by novel emerging strains with further neutralisation escape.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.19.23286159v1" target="_blank">Durable reprogramming of neutralising antibody responses following breakthrough Omicron infection</a>
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<li><strong>Bivalent COVID-19 vaccine antibody responses to Omicron variants suggest that responses to divergent variants would be improved with matched vaccine antigens</strong> -
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We compared neutralizing antibody responses to BA.4/5, BQ.1.1, XBB, and XBB.1.5 Omicron SARS-CoV-2 variants after a bivalent or ancestral COVID-19 mRNA booster vaccine or post-vaccination infection. We found that the bivalent booster elicited moderately high antibody titers against BA.4/5 that were approximately two-fold higher against all Omicron variants than titers elicited by the monovalent booster. The bivalent booster elicited low but similar titers against both XBB and XBB.1.5 variants. These findings inform risk assessments for future COVID-19 vaccine recommendations and suggest that updated COVID-19 vaccines containing matched vaccine antigens to circulating divergent variants may be needed.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.22.23286320v1" target="_blank">Bivalent COVID-19 vaccine antibody responses to Omicron variants suggest that responses to divergent variants would be improved with matched vaccine antigens</a>
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<li><strong>Was access and quality of healthcare affected during COVID-19 pandemic? A qualitative enquiry into healthcare access for non-communicable diseases in Central India</strong> -
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Objective: COVID-19 pandemic has had significant impacts on healthcare systems across the world. However, its impact on healthcare systems in Low- and Middle-Income Countries (LMICs) has been especially devastating, resulting in restricted access to healthcare. The present study was conducted to assess healthcare access for non-communicable diseases (NCDs) in Central India. Design: Inductive and deductive thematic analysis of in-depth semi-structured interviews. Setting: Study was conducted in communities of two urban and rural districts of central India. Participants: Interviewed participants included PLNCDs, their caregivers, community dwellers, CHWs such as, Accredited Social Health Activists (ASHAs) and Anganwadi Workers (AWWs), Medical Officers, and Community Leaders. Recruitment of the participants was done via purposive and convenience sampling. Result: A total of fifty Key Informant Interviews were (KIIs) conducted. All participants reported facing considerable difficulties while trying to access care from both public as well as private healthcare facilities. Absence of staff, equipment and medicines, restricted commute, misconceptions regarding the spread of COVID-19, and the stigma attached to COVID-19 infection acted as major barriers to accessing care, while door-to-door visits by community health workers, community support, and presence of privately owned healthcare facilities in the vicinity acted as facilitators. Conclusion: In our study, we found that continued functioning of primary healthcare centres, ensuring uninterrupted supply of medicine and effective dissemination of information regarding COVID-19 could have acted to ease access to healthcare. Going ahead, capacity building to offset the impact of future emergencies and pandemics should be a crucial consideration while developing resilient healthcare systems.
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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/10.1101/2023.02.23.23286390v1" target="_blank">Was access and quality of healthcare affected during COVID-19 pandemic? A qualitative enquiry into healthcare access for non-communicable diseases in Central India</a>
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</div></li>
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<li><strong>COVID-19 Booster Vaccination Strategy</strong> -
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Despite the fact that medical specialists believe COVID-19 vaccinations are successful in regulating the virus’s health consequences, demand in such vaccines among various communities has been quite low. On that basis, experts have questioned whether combining influenza vaccinations might improve vaccine uptake. The key reason for their hypothesis is that the number of persons obtaining influenza vaccinations outnumbers those interested in various COVID-19 vaccines. As a result, the current work entails a systematic review and meta-analysis of various research studies focusing on combining influenza and COVID-19 booster immunization to enhance vaccine uptake among groups severely impacted by the health pandemic. It is the appropriate time to undertake such systematic review and meta-analysis mainly because of the need to make informed health decisions on mitigating the health implications of such viruses, especially among diverse populations that are majorly affected by them.
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🖺 Full Text HTML: <a href="https://osf.io/2ye9p/" target="_blank">COVID-19 Booster Vaccination Strategy</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine<br/><b>Sponsors</b>: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran<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>Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: Aerobic exercise and strength training<br/><b>Sponsor</b>: Ukbe Sirayder<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluticasone; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Blood sampling<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: N-Acetylcysteine; Drug: Placebo<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: miRNA analysis in plasma<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator<br/><b>Sponsor</b>: Hebei Medical University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MGC Health COVID-19 & Flu A+B Home Multi Test Usability Study</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B<br/><b>Interventions</b>: Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test; Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test (2 to 13 y/o)<br/><b>Sponsors</b>: Medical Group Care, LLC; CSSi Life Sciences<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Washing COVID-19 Away With a Hypertonic Seawater Nasal Irrigation Solution</strong> - <b>Condition</b>: SARS-CoV2 Infection<br/><b>Intervention</b>: Other: Hypertonic seawater solution<br/><b>Sponsor</b>: Larissa University Hospital<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>Cognitive Rehabilitation for People With Cognitive Covid19</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Behavioral: Cognitive rehabilitation<br/><b>Sponsors</b>: University College, London; Bangor University; St George’s University Hospitals NHS Foundation Trust; University of Brighton; University Hospital Southampton NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust<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>Exercise Intervention Using mHealth in Patients With Post-Acute COVID-19 Syndrome: a Randomized Clinical Trial</strong> - <b>Conditions</b>: Post-Acute COVID19 Syndrome; Long COVID; Post COVID-19 Condition<br/><b>Interventions</b>: Device: COVIDReApp Group; Other: Control Group<br/><b>Sponsor</b>: University of Cadiz<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>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19<br/><b>Interventions</b>: Other: Individual Counseling; Other: Group Counseling; Other: Resources<br/><b>Sponsors</b>: New Mexico State University; National Institutes of Health (NIH)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Post COVID-19 REspiratory Mechanisms and the Efficacy of a Breathing Exercise Intervention for DYsregulated Breathing</strong> - <b>Conditions</b>: COVID-19; Respiratory Disease<br/><b>Intervention</b>: Other: Breathing techniques over 12 sessions / 6 weeks inc yoga<br/><b>Sponsor</b>: University of Nottingham<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1/2 Study to Assess the Safety and Immunogenicity of JCXH-221, an mRNA-based Broadly Protective COVID-19 Vaccine</strong> - <b>Conditions</b>: COVID-19; Infectious Disease<br/><b>Interventions</b>: Biological: JCXH-221; Biological: Active Comparator; Other: Placebo<br/><b>Sponsors</b>: Immorna Biotherapeutics, Inc.; ICON plc<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of SARS-CoV-2 M<sup>pro</sup> inhibitors containing P1’ 4-fluorobenzothiazole moiety highly active against SARS-CoV-2</strong> - COVID-19 caused by SARS-CoV-2 has continually been serious threat to public health worldwide. While a few anti-SARS-CoV-2 therapeutics are currently available, their antiviral potency is not sufficient. Here, we identify two orally available 4-fluoro-benzothiazole-containing small molecules, TKB245 and TKB248, which specifically inhibit the enzymatic activity of main protease (M^(pro)) of SARS-CoV-2 and significantly more potently block the infectivity and replication of various 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>Structural-based design of HD-TAC7 PROteolysis TArgeting chimeras (PROTACs) candidate transformations to abrogate SARS-CoV-2 infection</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for about 672 million infections and 6.85 million deaths worldwide. Upon SARS-CoV-2 infection, Histone deacetylases (HDACs) hyperactivate the pro-inflammatory response resulting in stimulation of Acetyl-Coenzyme A and cholesterol for viral entry. HDAC3 inhibition results in the anti-inflammatory activity and reduction of pro-inflammatory cytokines that may restrict COVID-19 progression. Here, we have designed 44…</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 immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial</strong> - CONCLUSION: Extended 8-week interval regimen of BNT162b2 induced higher neutralizing antibodies than a standard 3-week interval regimen. The third dose induced high neutralizing antibodies against the Omicron variant.</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>Sulforaphane is a reversible covalent inhibitor of 3-chymotrypsin-like protease of SARS-CoV-2</strong> - The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a major public health threat worldwide and emphasizes an urgent need for effective therapeutics. Recently, Ordonez et al. identified sulforaphane (SFN) as a novel coronavirus inhibitor both in vitro and in mice, but the mechanism of action remains elusive. In this study we independently discovered SFN for its inhibitory effect against SARS-CoV-2 using a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Correction: Lee et al. The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b. <em>Pharmaceutics</em> 2022, <em>14</em>, 1511</strong> - In the original publication […].</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL<sup>pro</sup> Protein</strong> - Recent studies have shown that the peptide [des-Cys<sup>(11),Lys</sup>(12),Lys^(13)-(p-BthTX-I)(2)K] (p-Bth) is a p-BthTX-I analog that shows enhanced antimicrobial activity, stability and hemolytic activity, and is easy to obtain compared to the wild-type sequence. This molecule also inhibits SARS-CoV-2 viral infection in Vero cells, acting on SARS-CoV-2 PL^(pro) enzymatic activity. Thus, the present study aimed to assess the effects of structural modifications to p-Bth, such as dimerization,…</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>Saponins: Research Progress and Their Potential Role in the Post-COVID-19 Pandemic Era</strong> - In the post-COVID-19 pandemic era, the new global situation and the limited therapeutic management of the disease make it necessary to take urgent measures in more effective therapies and drug development in order to counteract the negative global impacts caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new infectious variants. In this context, plant-derived saponins-glycoside-type compounds constituted from a triterpene or steroidal aglycone and one or more sugar…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>Melastoma malabathricum</em> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection</strong> - Platelet hyper-reactivity and neutrophil extracellular trap (NET) formation contribute to the development of thromboembolic diseases for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study investigated the pathophysiological effects of SARS-CoV-2 surface protein components and the viral double-stranded RNA (dsRNA) on platelet aggregation and NET formation. Traditional Chinese medicine (TCM) with anti-viral effects was also delineated. The treatment 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>Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition</strong> - Furin is a potential target protein associated with numerous diseases; especially closely related to tumors and multiple viral infections including SARS-CoV-2. Most of the existing efficient furin inhibitors adopt a substrate analogous structure, and other types of small molecule inhibitors need to be discovered urgently. In this study, a high-throughput screening combining virtual and physical screening of natural product libraries was performed, coupled with experimental validation 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>Papaverinol-<em>N</em>-Oxide: A Microbial Biotransformation Product of Papaverine with Potential Antidiabetic and Antiobesity Activity Unveiled with In Silico Screening</strong> - Bioconversion of biosynthetic heterocyclic compounds has been utilized to produce new semisynthetic pharmaceuticals and study the metabolites of bioactive drugs used systemically. In this investigation, the biotransformation of natural heterocyclic alkaloid papaverine via filamentous fungi was explored. Molecular docking simulations, using protein tyrosine phosphatase 1B (PTP1B), α-glucosidase and pancreatic lipase (PL) as target enzymes, were performed to investigate the antidiabetic potential…</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>Antiviral Effect of Ephedrine Alkaloids-Free Ephedra Herb Extract against SARS-CoV-2 In Vitro</strong> - We report for the first time that ephedrine alkaloids-free Ephedra Herb extract (EFE) directly inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and that the addition of EFE to the culture medium before viral infection reduces virus titers in the culture supernatant of SARS-CoV-2, including those of variant strains, by more than 99%, 24 h after infection. The addition of Ephedra Herb macromolecule condensed-tannin, which is the main active…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cross-Reactivity of Antibodies in Intravenous Immunoglobulin Preparation for Protection against SARS-CoV-2</strong> - Severe cases of COVID-19 continue to put pressure on medical operations by prolonging hospitalization, occupying intensive care beds, and forcing medical personnel to undergo harsh labor. The eradication of SARS-CoV-2 through vaccine development has yet to be achieved, mainly due to the appearance of multiple mutant-incorporating strains. The present study explored the utility of human intravenous immunoglobulin (IVIG) preparations in suppressing the aggravation of any COVID-19 infection using a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation</strong> - Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show immune evasion of vaccine-derived immunity, highlighting the need for better clinical immunogenicity biomarkers. To address this need, an enzyme-linked immunosorbent assay-based, human angiotensin-converting enzyme 2 (hACE2) binding inhibition assay was developed to measure antibodies against the ancestral strain of SARS-CoV-2 and was validated for precision, specificity, linearity, and other parameters. This…</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>Natural Flavonoid Derivatives Have Pan-Coronavirus Antiviral Activity</strong> - The SARS-CoV-2 protease (3CLpro) is one of the key targets for the development of efficacious drugs for COVID-19 treatment due to its essential role in the life cycle of the virus and exhibits high conservation among coronaviruses. Recent studies have shown that flavonoids, which are small natural molecules, have antiviral activity against coronaviruses (CoVs), including SARS-CoV-2. In this study, we identified the docking sites and binding affinity of several natural compounds, similar to…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reduction of Viral and Bacterial Activity by Using a Self-Powered Variable-Frequency Electrical Stimulation Device</strong> - Viruses and bacteria, which can rapidly spread through droplets and saliva, can have serious effects on people’s health. Viral activity is traditionally inhibited using chemical substances, such as alcohol or bleach, or physical methods, such as thermal energy or ultraviolet-light irradiation. However, such methods cannot be used in many applications because they have certain disadvantages, such as causing eye or skin injuries. Therefore, in the present study, the electrical stimulation method…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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