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176 lines
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<title>26 June, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Altered Rhythms of Ramadan: Temporalities of Social Media Non/Use during COVID-19</strong> -
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<div>
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This article explores how the relational context of religious rituals and practices and pandemic-induced stay-at-home orders shape the socio-temporal organization of young Muslims’ everyday social media engagement during Ramadan under COVID-19. We collected semi-structured interviews with 22 self-identified Muslims who observed Ramadan during the pandemic (in 2020 and 2021). Our findings point to the impacts of COVID-19 and related public health measures in the formation of the participants’ psyche about their observance of Ramadan in 2020 and 2021. Drawing on the concept of socio-temporal rhythms in everyday life practices, we map the temporal patterning of their everyday religious rituals and practices onto their social media (dis)engagement, as enabled or constrained by pandemic restrictions.
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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/enmd4/" target="_blank">Altered Rhythms of Ramadan: Temporalities of Social Media Non/Use during COVID-19</a>
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</div></li>
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<li><strong>Childbearing desires before and after the Covid-19 outbreak in Australia: Who changed their attitudes toward having a first or additional child?</strong> -
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<div>
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Using a quasi-experimental cohort design, this study examines whether childbearing desires were affected by the Covid-19 pandemic, and investigates which pandemic-related factors have affected childbearing desires the most. To address these questions, a unique panel dataset is used, collected before and after the outbreak of Covid-19 in Australia. Results show that parents who already had one child were the most likely to experience a decline in childbearing desires as a result of the pandemic, while childbearing desires were most stable among those who were childless. Economic and employment related factors did not appear to be of great relevance in predicting changes in childbearing plans, however of strong importance were changes to the quality of couple relationships and of social support from family and friends.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/qbgmp/" target="_blank">Childbearing desires before and after the Covid-19 outbreak in Australia: Who changed their attitudes toward having a first or additional child?</a>
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</div></li>
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<li><strong>Business Continuity During the COVID-19 Pandemic Era: Surviving and Improving the Quality Process Management System</strong> -
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<div>
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Worldwide health and the global economy have been heavily damaged by the COVID-19 pandemic,with business continuity being the primary issue of every company operating in the health industry. A criticalinstrument for enterprises’ survival is the establishment of a business continuity management system that enablesthem to manage risks, discover opportunities created by the pandemic, and secure their continuity. The purposeof this paper is to examine how a pharmaceutical firm may ensure business continuity by adopting ISO22301:2019 in parallel with the existing ISO 9001:2015 quality standard, as well as the similarities anddifferences between the two management standards. According to the results, the pharmaceutical company,whose case was studied, managed to create an effective action plan in order to mitigate at an acceptable level theidentified risks, to maintain its business continuity and to ensure the quality of the product and the health of thepatients and its employees.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/mdje5/" target="_blank">Business Continuity During the COVID-19 Pandemic Era: Surviving and Improving the Quality Process Management System</a>
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</div></li>
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<li><strong>Environmental Policy Issues and Public Health Concerns Associated with Rohingya Refugee Population in Bangladesh</strong> -
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<div>
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Introduction: The Rohingya population in Myanmar has been adversely affected by the Citizenship Act of 1982. This Act opted out of them from the list of recognized ethnic minorities and deprived them of civil rights and public services. As a result, the Myanmar army started a massive cleaning operation in the Rohingya community where thousands of Rohingyas were killed, and 750,000 refugees fled to Bangladesh. The Government of Bangladesh is helping this migrant community to settle in Bangladesh with the support of multiple national and international nonprofit organizations. This paper aims to explain the policy challenges in accommodating the Rohingya refugees from an environmental policy and public health perspective. Methodology: In this study, the researchers collected secondary data from multiple sources, such as journal articles, websites of internationally renowned organizations, and the health record of clinics supported by OBAT Helpers, Inc., a U.S.-based nonprofit, who are providing healthcare services to the Rohingya community living in multiple camps. The collected information is summarized systematically to understand the risks to the environment and health conditions in the Rohingya refugee camps that occurred due to a lacking policy readiness and logistic unpreparedness of the government. These issues are very critical not only for the migrant population but also for the host community. Findings: Approximately 860,175 Rohingya Refugees have been placed in 34 camps located in multiple districts in Bangladesh since 2017. To accommodate this large population in Bangladesh, the government had to cut the forest and fill out water bodies. Therefore, deforestation and building houses near cliff areas cause soil erosion and create risks for marine resources. In these camps, the refugees use fuelwood and kerosene for cooking, which increases particle pollution in the air. The overpopulated camps are having issues with the inexistence of ventilation. In the past couple of years, there were several massive fire incidents where hundreds of houses were burnt, and many people were injured and dead. Besides, building new houses for the refugees sets the local biodiversity at critical risk. The Kutupalong camp blocked the only corridor for the Asian elephants and trapped them in a corner of that area. In this challenging situation, the elephants invade nearby camp areas for food. As a result, 13 people died in a human-elephant conflict. Along with the environmental issues, the health condition in these refugee camps is very critical for different age groups and sex. Unplanned water and sewerage system are also polluting the water bodies which is increasing water-borne diseases in the community. The most common diseases found in these clinics are communicable, such as upper respiratory tract infection (URTI), skin disease, cough and cold, diarrhea, chickenpox, respiratory tract infection, fever, measles/rubella, and sexually transmitted disease, and malnutrition. In the past several decades, the Government of Bangladesh has been successfully working root-level to end chronic diseases, such as diphtheria, polio, whooping cough, tetanus, tuberculosis, chickenpox, and cholera which are crucial not only for the babies but for the community. The healthcare services of OBAT Health clinics have found many cases of these chronic diseases among the Rohingya refugees which may bring new threats to public health situations in Bangladesh. The congested environment of the camps spreads communicable diseases including COVID-19. Besides, thousands of patients in the camps are diagnosed with psychological trauma and gender-based violence in multiple age groups. More healthcare facilities are needed in these camps to provide mental healthcare services and support sexually assaulted victims. Conclusion: The government of Bangladesh and multiple national and international organizations are supporting the Rohingya refugees to live with basic human rights and security in Bangladesh. However, accommodating a large number of Rohingya refugees in a very short time causes multiple environmental issues and public health concerns. Policy readiness and logistic preparedness are necessary to reduce these long-term environmental challenges and public health concerns in the refugee camps and the nearby host communities. Planned zoning of the refugee camps and forestation would minimize the harm to land, water bodies, and biodiversity. Providing renewable or clean energy would help reduce PM pollution in the air quality. In addition to that, health education, awareness for immunization and vaccination, and adequate healthcare facilities for physical and mental healthcare would help to minimize health risks in this community. All these proposed solutions require support for policy intervention at both national and international levels. It will help to minimize the risk of climate change and public health issues globally.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/as8km/" target="_blank">Environmental Policy Issues and Public Health Concerns Associated with Rohingya Refugee Population in Bangladesh</a>
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</div></li>
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<li><strong>SARS-CoV-2 evolution and evasion from multiple antibody treatments in a cancer patient</strong> -
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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients may lead to accelerated viral mutation rate, immune evasion and persistent viral shedding over many months. Here we report the case of a severely immunocompromised cancer patient infected with the Delta variant of SARS-CoV-2 for over 8 months. Genome sequencing of samples taken after repeated monoclonal antibody treatments reveal the emergence and accumulation of mutations enabling escape from neutralization by antibodies. Mutations emerging in accessory and non-structural viral proteins target specific residues of immunomodulatory domains, potentially leading to loss of some functions, while preserving others. The mutated virus managed to completely overcome neutralization by monoclonal antibodies while remaining viable and infective. Our results suggest that the loss of specific immunomodulatory viral functions might confer a selective advantage in immunocompromised hosts. We also compare between mutations emerging in the presence and absence of neutralizing antibodies.
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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/10.1101/2022.06.25.22276445v1" target="_blank">SARS-CoV-2 evolution and evasion from multiple antibody treatments in a cancer patient</a>
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<li><strong>Differentials in clinical severity and other patient activity indicators amongst Black and South Asian cancer patients in England</strong> -
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The link between ethnicity, deprivation and health inequalities is well-established. The relationship between ethnicity and cancer is more complex and influenced by a variety of socio-economic, cultural and physiological factors. Understanding the relationship between ethnicity and patient care indicators for specific cancer types is vital if NHS England is to meet the UK government’s stated priority to reduce health inequalities as it recovers from COVID-19. This paper explores the impact of ethnicity on clinical severity, treatment costs and a range of patient activity indicators across three cancer types – chronic lymphocytic leukaemia, multiple myeloma and prostate cancer. The paper uses a dataset derived from the Hospital Episodes Statistics (secondary care) database covering 2016/17 to 2020/21,. This enabled the differential impact of the pandemic on ethnic minority patients to be considered. The data was aggregated by ethnicity and deprivation quintile at a national and Integrated Care System (ICS) level. Clinical severity was proxied using co-morbidity and complications (CC) scores. Multivariate linear regression (OLS) models were used to explore the associations with ethnicity. Black and South Asian patients CC scores were 12.2% and 15.8% higher than the population average (4.1). Controlling for socio-economic deprivation, South Asian patients had higher average clinical severity (+0.57, p<0.01). In addition, ICSs with large South Asian populations were associated with higher CC scores (+0.69, p<0.01). Treatment costs were higher for Black prostate cancer patients with interventions (+£842, p<0.001) and South Asian multiple myeloma patients (+£1686, p<0.001). Both Black and South Asian patients tend to have more spells in hospital. COVID-19 saw total inpatient admissions fall by 18.9%. Black and South Asian inpatient admissions fell by 1.9 and 2.9 percentage points more than the national average respectively. Average clinical severity increased by 7.1% with the largest increase amongst South Asian (+11.5%) and Black (+8.1%) patients. The higher clinical severity in South Asian patients and higher treatment costs in Black patients observed in this study are not accompanied by significant variations in patient activity indicators, which may point to drivers associated with delays to diagnosis or barriers to access to primary care.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.24.22276862v1" target="_blank">Differentials in clinical severity and other patient activity indicators amongst Black and South Asian cancer patients in England</a>
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<li><strong>A Bivalent Omicron-containing Booster Vaccine Against Covid-19</strong> -
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Background Updated vaccination strategies against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern are needed. Interim results of the safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster candidate are presented. Methods In this ongoing, phase 2/3 trial, the 50-μg bivalent vaccine mRNA-1273.214 (25-μg each ancestral Wuhan-Hu-1 and omicron B.1.1.529 spike SARS-CoV-2 mRNAs) was compared to the authorized 50-μg mRNA-1273 booster in adults who previously received 2-dose primary series of 100-μg mRNA-1273 and a first booster dose of 50-μg mRNA-1273 at least 3 months prior. Primary objectives were safety and reactogenicity, and immunogenicity of 50-μg mRNA-1273.214 compared with 50-μg mRNA-1273. Immunogenicity data 28 days after the booster dose are presented. Results Four hundred thirty-seven and 377 participants received 50-μg of mRNA-1273.214, or mRNA-1273, respectively. Median time between first and second booster doses of mRNA-1273.214 and mRNA-1273 were similar (136 and 134 days, respectively). In participants with no prior SARS-CoV-2 infection, observed omicron neutralizing antibody geometric mean titers (GMTs [95% confidence interval]) after the mRNA-1273.214 and mRNA-1273 booster doses, were 2372.4 (2070.6−2718.2) and 1473.5 (1270.8−1708.4) respectively and the model-based GMT ratio (97.5% confidence interval) was 1.75 (1.49−2.04). All pre-specified non-inferiority (ancestral SARS-CoV-2 with D614G mutation [D614G] GMT ratio; ancestral SARS-CoV-2 [D614G] and omicron seroresponse rates difference) and superiority primary objectives (omicron GMT ratio) for mRNA-1273.214 compared to mRNA-1273 were met. Additionally, mRNA-1273.214 50-μg induced a potent neutralizing antibody response against omicron subvariants BA.4/BA.5 and higher binding antibody responses against alpha, beta, gamma, delta and omicron variants. Safety and reactogenicity profiles were similar and well-tolerated for both vaccines groups. Conclusion The bivalent vaccine mRNA-1273.214 50-μg was well-tolerated and elicited a superior neutralizing antibody response against omicron, compared to mRNA-1273 50-μg, and a non-inferior neutralizing antibody response against the ancestral SARS-CoV-2 (D614G), 28 days after immunization, creating a new tool as we respond to emerging SARS-CoV-2 variants.
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</p>
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</div>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.24.22276703v1" target="_blank">A Bivalent Omicron-containing Booster Vaccine Against Covid-19</a>
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<li><strong>Iterative cycles in qualitative research: Introducing the RREAL Sheet as an innovative process</strong> -
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Qualitative research is increasingly becoming a valued resource in time-sensitive contexts where study findings are required promptly to inform changes in policy and practice. The field of rapid qualitative research has generated tools to enable prompt data collection and analysis, frequently relying on the use of tables or matrices to facilitate the categorisation and interpretation of qualitative data. Missing from the literature, are working documents or flexible processes that can help qualitative researchers to synthesize data as data collection is ongoing. This paper describes the use of the RREAL Sheet, a tool developed by our team to facilitate the identification of gaps during data collection, the collaborative interpretation and sense-making of findings and the synthesis of findings so these can be shared with stakeholders in real-time. We provide a step-by-step description for the design and use of RREAL sheets, and critically engage with their benefits and limitations. We also describe a case example of using the sheets in a recent study that focused on exploring the perceptions and experiences of healthcare workers delivering care during the COVID-19 pandemic in the UK. We argue that RREAL sheets can be a valuable tool for qualitative researchers interested in conducting responsive research where findings can be actively used by a wide range of stakeholders.
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🖺 Full Text HTML: <a href="https://osf.io/9dp2w/" target="_blank">Iterative cycles in qualitative research: Introducing the RREAL Sheet as an innovative process</a>
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<li><strong>Online Learning Quality, Satisfaction, and Word-of-Mouth Promotion</strong> -
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This study aimed to verify and analyze the two influences. The first was the effect of online learning quality (OLQ) on student satisfaction and word-of-mouth (WOM) promotion. The second was the impact of student satisfaction on WOM promotion. Then, we used the population of 137 students taking online classes during the COVID-19 pandemic at Indonesia’s Interkultural Edukasi Partner (IEP) in Bandung to support this intention. Furthermore, we applied the Slovin formula with a 5% border of fault to obtain a sample size of 103. After getting it, the samples were taken by simple random sampling. Unfortunately, only 45 students responded by filling out the questionnaire distributed. As a result, this study utilized the structural equation model based on variance to examine the proposed hypotheses. After testing and discussing them, this research concluded that OLQ positively influenced student satisfaction, but OLQ did not. Besides, student satisfaction positively affected this promotion.
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</div>
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🖺 Full Text HTML: <a href="https://osf.io/gq3rh/" target="_blank">Online Learning Quality, Satisfaction, and Word-of-Mouth Promotion</a>
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<li><strong>Defining the Ligand-dependent Interactome of the Sigma 1 Receptor</strong> -
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Sigma 1 Receptor (S1R) is a therapeutic target for a wide spectrum of pathological conditions ranging from neurodegenerative diseases to cancer and COVID-19. S1R is ubiquitously expressed throughout the visceral organs, nervous, immune and cardiovascular systems. It is proposed to function as a ligand-dependent molecular chaperone that modulates multiple intracellular signaling pathways. The purpose of this study was to define the S1R interactome under native conditions and upon binding to well-characterized ligands. This was accomplished by fusing the biotin ligase, Apex2, to the C terminus of S1R. Cells stably expressing S1R-Apex or a GFP-Apex control were used to map specific protein interactions. Biotinylated proteins were labeled under native conditions and in a ligand dependent manner, then purified and identified using quantitative mass spectrometry. Under native conditions, S1R biotinylates over 200 novel proteins, many of which localize within the endomembrane system (ER, Golgi, secretory vesicles) and function within the secretory pathway. Under conditions of cellular exposure to either S1R agonist or antagonist, results show enrichment of proteins integral to secretion, extracellular matrix formation, and cholesterol biosynthesis. Notably, Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) displays increased binding to S1R under conditions of treatment with Haloperidol, a well-known S1R antagonist; whereas Low density lipoprotein receptor (LDLR) binds more efficiently to S1R upon treatment with (+)-Pentazocine ((+)-PTZ), a classical S1R agonist. Our results are consistent with the postulated role of S1R as an intracellular chaperone and further suggest important and novel functionalities related to cholesterol metabolism and biosynthesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.22.497210v1" target="_blank">Defining the Ligand-dependent Interactome of the Sigma 1 Receptor</a>
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<li><strong>Predicting the antigenic evolution of SARS-COV-2 with deep learning</strong> -
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The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) antigenic profile evolves in response to the vaccine and natural infection-derived immune pressure, resulting in immune escape and threatening public health. Exploring the possible antigenic evolutionary potentials improves public health preparedness, but it is limited by the lack of experimental assays as the sequence space is exponentially large. Here we introduce the Machine Learning-guided Antigenic Evolution Prediction (MLAEP), which combines structure modeling, multi-task learning, and genetic algorithm to model the viral fitness landscape and explore the antigenic evolution via in silico directed evolution. As demonstrated by existing SARS-COV-2 variants, MLEAP can infer the order of variants along antigenic evolutionary trajectories, which is also strongly correlated with their sampling time. The novel mutations predicted by MLEAP are also found in immunocompromised covid patients and newly emerging variants, like BA. 4/5. In sum, our approach enables profiling existing variants and forecasting prospective antigenic variants, thus may help guide the development of vaccines and increase preparedness against future variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.23.497375v1" target="_blank">Predicting the antigenic evolution of SARS-COV-2 with deep learning</a>
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<li><strong>A cell-based, spike protein binding assay highlights differences in antibody neutralising capacity for SARS-CoV-2 variants</strong> -
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The engagement of the SARS-CoV-2 spike protein with ACE2 is a critical step for viral entry to human cells and accordingly blocking this interaction is a major determinant of the efficacy of monoclonal antibody therapeutics and vaccine-elicited serum antibodies. The emergence of SARS-CoV-2 variants necessitates the development of adaptable assays that can be applied to assess the effectiveness of therapeutics. Through testing of a range of recombinant spike proteins, we have developed a cell based, ACE2/spike protein binding assay that characterises monoclonal anti-spike protein antibodies and neutralising antibodies in donor serum. The assay uses high-content imaging to quantify cell bound spike protein fluorescence. Using spike proteins from the original “Wuhan” SARS-CoV-2 virus, as well as the delta and omicron variants, we identify differential blocking activity of three monoclonal antibodies directed against the spike receptor binding domain. Importantly, biological activity in the spike binding assay translated to efficacy in a SARS-CoV-2 infection assay. Hence, the spike binding assay has utility to monitor anti-spike antibodies against the major known SARS-CoV-2 variants and is readily adaptable to quantify impact of antibodies against new and emerging SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.24.496409v1" target="_blank">A cell-based, spike protein binding assay highlights differences in antibody neutralising capacity for SARS-CoV-2 variants</a>
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<li><strong>Investigating the mutations in the SARS-CoV-2 proteins among European countries</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new member of the Coronaviridae family, triggering more than 190 million cases and more than two million deaths in European societies. Emerging the new variants due to mutations in genomic regions are foremost responsible for influencing the infectivity and mortality potential of such a virus. In the current study, we considered mutations among spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 in the Europe continent by exploring the frequencies of mutations and the timeline of emerging them. For this purpose, Amino-acid sequences (AASs) were gathered from the GISAID database, and Mutation tracking was performed by detecting any difference between samples and a reference sequence; Wuhan-2019. In the next step, we compared the achieved results with worldwide sequences. 8.6%, 63.6%, 24.7%, and 1.7% of S, E, M, and N samples did not demonstrate any mutation among European countries. Also, the regions of 508 to 635 AA, 7 to 14 AA, 66 to 88 AA, and 164 to 205 AA in S, E, M, and N samples contained the most mutations relative to the total AASs in both Europe AASs and worldwide samples. D614G, A222V, S477N, and L18F were the first to fifth frequent mutations in S AASs among European samples, and T9I, I82T, and R203M were the first frequent mutations among E, M, and S AASs of the Europe continent. Investigating the mutations among structural proteins of SARS-CoV-2 can improve the strength of therapeutic and diagnostic strategies to efficient combat the virus and even maybe efficient in predicting new emerging variants of concern.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.23.497239v1" target="_blank">Investigating the mutations in the SARS-CoV-2 proteins among European countries</a>
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<li><strong>DESIGN OF A CHIMERIC ACE-2/Fc-SILENT FUSION PROTEIN WITH ULTRAHIGH AFFINITY AND NEUTRALIZING CAPACITY FOR SARS-CoV-2 VARIANTS</strong> -
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As the coronavirus SARS-CoV-2 continues to mutate into Variants of Concern (VOC), there is a growing and urgent need to develop effective antivirals to combat the newly emerged infectious disease COVID-19. Recent data indicate that monoclonal antibodies developed early in the pandemic are no longer capable of effectively neutralizing currently active VOCs. This report describes the design of a class of variant-agnostic chimeric molecules consisting of an Angiotensin Converting Enzyme-2 (ACE-2) domain mutated to retain ultrahigh affinity binding to a wide variety of SARS-CoV-2 variants, coupled to an Fc-silent immunoglobulin domain that eliminates antibody-dependent enhancement (ADE) and simultaneously extends biological half-life compared to existing mABs. Molecular modeling revealed that ACE-2 mutations L27, V34 and E90 resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM, 507 pM and 73 pM for binding to the Alpha B1.1.7, Delta B.1.617.2 and Omicron B.1.1.529 variants, and notably, 78fM affinity to the Omicron BA.2 variant, respectively. Surrogate viral neutralization assays (sVNT) revealed titers of [≥]4.9ng/ml, for neutralization of recombinant viral proteins corresponding to the Alpha, Delta and Omicron variants. The values above were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. It is proposed that this new class of chimeric ACE-2/mABs will constitute variant-agnostic and cost-effective prophylactics against SARS-CoV-2, particularly when administered by nasal delivery systems.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.23.497326v1" target="_blank">DESIGN OF A CHIMERIC ACE-2/Fc-SILENT FUSION PROTEIN WITH ULTRAHIGH AFFINITY AND NEUTRALIZING CAPACITY FOR SARS-CoV-2 VARIANTS</a>
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<li><strong>Monitoring SARS-CoV-2 infection using a double reporter-expressing virus</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the highly contagious agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. An essential requirement for understanding SARS-CoV-2 fundamental biology and the impact of anti-viral therapeutics are robust methods to detect for the presence of the virus in infected cells or animal models. Despite the development and successful generation of recombinant (r)SARS-CoV-2 expressing fluorescent or luciferase reporter genes, knowledge acquired from their use in in vitro assays and/or in live animals are limited to the properties of the fluorescent or luciferase reporter genes. Herein, for the first time, we engineered a replication-competent rSARS-CoV-2 that expresses both fluorescent (mCherry) and luciferase (Nluc) reporter genes (rSARS-CoV-2/mCherry-Nluc) to overcome limitations associated with the use of a single reporter gene. In cultured cells, rSARS-CoV-2/mCherry-Nluc displayed similar viral fitness as rSARS-CoV-2 expressing single reporter fluorescent and luciferase genes (rSARS-CoV-2/mCherry and rSARS-CoV-2/Nluc, respectively), or wild-type (WT) rSARS-CoV-2, while maintaining comparable expression levels of both reporter genes. In vivo, rSARS-CoV-2/mCherry-Nluc has similar pathogenicity in K18 human angiotensin converting enzyme 2 (hACE2) transgenic mice than rSARS-CoV-2 expressing individual reporter genes, or WT rSARS-CoV-2. Importantly, rSARS-CoV-2/mCherry-Nluc facilitates the assessment of viral infection and transmission in golden Syrian hamsters using in vivo imaging systems (IVIS). Altogether, this study demonstrates the feasibility of using this novel bireporter-expressing rSARS-CoV-2 for the study SARS-CoV-2 in vitro and in vivo.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.23.497376v1" target="_blank">Monitoring SARS-CoV-2 infection using a double reporter-expressing virus</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>Immunosuppression and COVID-19 Boosters</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: diphtheria and tetanus toxoids (adsorbed) vaccine; Biological: COVID-19 vaccine<br/><b>Sponsors</b>: Kirby Institute; Seqirus Pty Ltd, Australia; Medical Research Future Fund (MRFF)<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>Discussing COVID-19 Vaccines in Private Facebook Groups</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Gist messages on COVID-19 vaccination; Behavioral: COVID-19 vaccine information<br/><b>Sponsor</b>: George Washington 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>Home-Based Exercise Tele-Rehabilitation After COVID-19</strong> - <b>Condition</b>: Post SARS-CoV2 (COVID-19)<br/><b>Intervention</b>: Other: Tele-exercise<br/><b>Sponsors</b>: VA Office of Research and Development; Baltimore Veterans Affairs Medical Center; Salem Veterans Affairs Medical Center<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>IMM-BCP-01 in Mild to Moderate COVID-19</strong> - <b>Conditions</b>: SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Drug: IMM-BCP-01; Drug: Placebo<br/><b>Sponsors</b>: Immunome, Inc.; United States Department of Defense<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>Calcitriol Supplementation in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Vitamin D Deficiency<br/><b>Intervention</b>: Drug: Calcitriol<br/><b>Sponsor</b>: RenJi Hospital<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>Olfactory Training in COVID-19 Associated Loss of Smell</strong> - <b>Conditions</b>: COVID-19; Hyposmia<br/><b>Intervention</b>: Device: Sniffin’ sticks Duftquartett<br/><b>Sponsor</b>: Medical University Innsbruck<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>Psychological Impact of Medical Evacuations on Families of Patients Admitted to Intensive Care Unit for Severe COVID-19</strong> - <b>Conditions</b>: COVID-19; Stress Disorders, Post-Traumatic<br/><b>Interventions</b>: Other: Revised Impact of Event Scale; Other: Hospital Anxiety and Depression scale; Other: 36-Item Short Form Survey; Other: satisfaction survey; Other: semi-directed interview with trusted person on the general experience of the patient’s medical evacuation; Other: semi-directed interview with trusted person on the general experience of hospitalization in intensive care<br/><b>Sponsor</b>: Centre Hospitalier Metropole Savoie<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>Effect of COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men.</strong> - <b>Conditions</b>: Infertility, Male; COVID-19<br/><b>Intervention</b>: Other: diagnostic test and sperm analysis<br/><b>Sponsors</b>: Comenius University; GYN-FIV<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 Study to Evaluate Immunogenicity and Safety of MVC-COV1901 Vaccine Compared With AZD1222</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: MVC-COV1901; Biological: AZD1222<br/><b>Sponsor</b>: Medigen Vaccine Biologics Corp.<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>COVID-19 Vaccine Uptake Trial</strong> - <b>Conditions</b>: Vaccination Refusal; COVID-19<br/><b>Interventions</b>: Other: Short Message Service (SMS) + Website Link Strategy; Other: Phone Call with Peer Strategy<br/><b>Sponsor</b>: Washington University School of Medicine<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>Laser Therapy on Tension-type Cephalea and Orofacial Pain in Post-covid-19 Patients</strong> - <b>Conditions</b>: Tension-Type Headache; Orofacial Pain; COVID-19<br/><b>Intervention</b>: Radiation: Photobimodulation<br/><b>Sponsor</b>: University of Nove de Julho<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>Cardiovascular Autonomic and Immune Mechanism of Post COVID-19 Tachycardia Syndrome</strong> - <b>Conditions</b>: Post-acute COVID-19 Syndrome; Postural Tachycardia Syndrome (POTS); Long COVID; SARS CoV 2 Infection<br/><b>Interventions</b>: Diagnostic Test: Determine the inflammatory and immune profile of post-COVID-19 POTS patients; Diagnostic Test: Measurement of PNS activity by HRV (Heart rate Variation); Diagnostic Test: Autonomic Symptoms assessment<br/><b>Sponsors</b>: Vanderbilt University Medical Center; American Heart Association<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>Clinical Trial of SARS-CoV-2 mRNA Vaccine(LVRNA009) as Heterologous Booster in Islamabad</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Biological: LVRNA009; Biological: CoronaVac®<br/><b>Sponsor</b>: AIM Vaccine Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>STEP-COVID: A Program for Pregnant Women During the SARS-CoV-2 Pandemic</strong> - <b>Conditions</b>: Psychological; Mental Health Issue; Prenatal Stress; Maternal Distress; COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: STEP-COVID<br/><b>Sponsors</b>: Université du Québec à Trois-Rivières; Public Health Agency of Canada (PHAC); Canada Research Chairs Endowment of the Federal Government of Canada<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>Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HLX70; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Henlius Biotech; Hengenix Biotech Inc; Sanyou Biopharmaceuticals(Shanghai)Co., Ltd; Shanghai ZJ Bio-Tech Co., Ltd<br/><b>Withdrawn</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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Induction of a Cytokine Storm Involves Suppression of the Osteopontin-Dependent TH1 Response</strong> - Cytokine release syndromes represent a severe turn in certain disease states, which may be caused by several infections, including those with the virus SARS-CoV-2. This inefficient, even harmful, immune response has been associated with a broad release of chemokines. Although a cellular (type I) immune reaction is efficacious against viral infections, we noted a type I deficit in the cytokine patterns produced by cytokine storms of all reported etiologies. Agents including lipopolysaccharide…</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>MicroRNAs in the development of potential therapeutic targets against COVID-19: A narrative review</strong> - CONCLUSION: This review summarizes several studies revealing the involvement of miRNAs in diverse and complex processes during the infection process of SARS-CoV-2. The miRNAs can substantially reduce the viral load by degradation of viral RNA and reduced expression of ACE2 receptors, besides mitigating the deleterious consequences of the exaggerated secretion of cytokines. Extensive investigations need to be done by the scientific community to utilize the miRNA based strategies 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>COVID-19 vaccine hesitancy among health service providers: A single centre experience from Karachi, Pakistan</strong> - CONCLUSIONS: A lack of trust in the safety and efficacy data of the available Chinese vaccines appeared as a factor inducing hesitancy. The resistance of younger respondents, especially trainee physicians, was a finding of concern since they form the backbone of the health system in the country.</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>Matched Versus Mixed COVID-19 Vaccinations in Korean Solid Organ Transplant Recipients: An Observational Study</strong> - CONCLUSIONS: The ChAd/BNT group showed higher humoral immunogenicity than the AdV-Vec group, with similar immunogenicity to the mRNA vaccine. Nevertheless, immunogenicity following the primary vaccination series was poor in all vaccine groups, supporting the justification for booster vaccination in SOTRs.</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>Rationale of using the dual chemokine receptor CCR2/CCR5 inhibitor cenicriviroc for the treatment of COVID-19</strong> - Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created a global pandemic infecting over 230 million people and costing millions of lives. Therapies to attenuate severe disease are desperately needed. Cenicriviroc (CVC), a C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 2 (CCR2) antagonist, an agent previously studied in advanced clinical trials for patients with HIV or nonalcoholic steatohepatitis (NASH), may…</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 universal DNA aptamer as an efficient inhibitor against spike-protein/hACE2 interactions</strong> - A universal aptamer against spike-proteins of diverse SARS-CoV-2 variants was discovered via DNA SELEX towards the wild-type (WT) spike-protein. This aptamer, A1C1, binds to the WT spike-protein or other variants of concern such as Delta and Omicron with low nanomolar affinities. A1C1 inhibited the interaction between hACE2 and various spike-proteins by 85-89%. This universal A1C1 aptamer can be used to design diagnostic and therapeutic molecular tools to target SARS-CoV-2 and its variants.</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>SARS-CoV-2 M Protein Facilitates Malignant Transformation of Breast Cancer Cells</strong> - Coronavirus disease 2019 (COVID-19) has spread faster due to the emergence of SARS-CoV-2 variants, which carry an increased risk of infecting patients with comorbidities, such as breast cancer. However, there are still few reports on the effects of SARS-CoV-2 infection on the progression of breast cancer, as well as the factors and mechanisms involved. In the present study, we investigated the impact of SARS-CoV-2 proteins on breast cancer cells (BCC). The results suggested that SARS-CoV-2 M…</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>Antifibrotic Mechanism of Piceatannol in Bleomycin-Induced Pulmonary Fibrosis in Mice</strong> - Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by myofibroblast accumulation and extracellular matrix deposition, which lead to irreversible damage of the lung’s architecture and the formation of fibrotic lesions. IPF is also a sequela in serious patients with the coronavirus disease 2019 (COVID-19). The molecular mechanisms under pulmonary fibrosis remain unclear, and there is no satisfactory treatment currently available….</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>Inhibitors of Activin Receptor-like Kinase 5 Interfere with SARS-CoV-2 S-Protein Processing and Spike-Mediated Cell Fusion via Attenuation of Furin Expression</strong> - Screening of a protein kinase inhibitor library identified SB431542, targeting activin receptor-like kinase 5 (ALK5), as a compound interfering with SARS-CoV-2 replication. Since ALK5 is implicated in transforming growth factor β (TGF-β) signaling and regulation of the cellular endoprotease furin, we pursued this research to clarify the role of this protein kinase for SARS-CoV-2 infection. We show that TGF-β1 induces the expression of furin in a broad spectrum of cells including Huh-7 and Calu-3…</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>Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses</strong> - In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study…</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>Nucleopore Traffic Is Hindered by SARS-CoV-2 ORF6 Protein to Efficiently Suppress IFN-β and IL-6 Secretion</strong> - A weak production of INF-β along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins that are able to counteract the host immune system, which is believed to be one of the most important features contributing to the viral pathogenesis and development of a severe clinical outcomes. Previous reports demonstrated that the SARS-CoV-2 ORF6 protein strongly suppresses INF-β production by…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High Incidence of SARS-CoV-2 Variant of Concern Breakthrough Infections Despite Residual Humoral and Cellular Immunity Induced by BNT162b2 Vaccination in Healthcare Workers: A Long-Term Follow-Up Study in Belgium</strong> - To mitigate the massive COVID-19 burden caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccination campaigns were initiated. We performed a single-center observational trial to monitor the mid- (3 months) and long-term (10 months) adaptive immune response and to document breakthrough infections (BTI) in healthcare workers (n = 84) upon BNT162b2 vaccination in a real-world setting. Firstly, serology was determined through immunoassays. Secondly, antibody…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Characterization of SARS-CoV-2 Evasion: Interferon Pathway and Therapeutic Options</strong> - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. SARS-CoV-2 is characterized by an important capacity to circumvent the innate immune response. The early interferon (IFN) response is necessary to establish a robust antiviral state. However, this response is weak and delayed in COVID-19 patients, along with massive pro-inflammatory cytokine production. This dysregulated innate immune response contributes to pathogenicity and in some…</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>Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds</strong> - Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic…</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>Carriers of <em>ADAMTS13</em> Rare Variants Are at High Risk of Life-Threatening COVID-19</strong> - Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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