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184 lines
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<title>28 December, 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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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Estimating the transmission dynamics of Omicron in Beijing, November to December 2022</strong> -
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We tracked the effective reproduction number Rt of SARS-CoV-2 Omicron BF.7 in Beijing in November-December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on November 1-11 (when the zero-covid interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on December 10-22 and self-reported to have been previously test-positive since November 1. After the announcement of “20 measures”, we estimated that Rt increased to 3.44 (95% CrI: 2.82-4.14) on November 18 and the infection incidence peaked on December 11. The cumulative infection attack rate (i.e. the proportion of population who have been infected since November 1) was 43.1% (95% CrI: 25.6-60.9) on December 14 and 75.7% (95% CrI: 60.7-84.4) on December 22. Surveillance programmes should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22283522v2" target="_blank">Estimating the transmission dynamics of Omicron in Beijing, November to December 2022</a>
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</div></li>
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<li><strong>Viral and host small RNA transcriptome analysis of SARS-CoV-1 and SARS-CoV-2-infected human cells reveals novel viral short RNAs.</strong> -
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<div>
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RNA viruses have been shown to express various short RNAs, some of which have regulatory roles during replication, transcription, and translation of viral genomes. However, short viral RNAs (svRNAs) generated by SARS-CoV-1 and SARS-CoV-2 remained largely unexplored, mainly due limitations of the widely used library preparation methods for small RNA deep sequencing and corresponding data processing. By analyzing publicly available small RNA-seq datasets, we observed that human cells infected by SARS-CoV-1 or SARS-CoV-2 produce multiple short viral RNAs (svRNAs), ranging in size from 15 to 26 nt and deriving predominantly from (+) RNA strands. In addition, we verified the presence of the five most abundant SARS-CoV-2 svRNAs in SARS-CoV-2-infected human lung adenocarcinoma cells by qPCR. Interestingly, the copy number of the observed SARS-CoV-2 svRNAs dramatically exceeded the expression of previously reported viral miRNAs in the same cells. We hypothesize that the reported SARS-CoV-2 svRNAs could serve as biomarkers for early infection stages due to their high abundance. Finally, we found that both SARS-CoV-1 and SARS-CoV-2 infection induced up- and down-regulation of multiple endogenous human short RNAs that align predominantly to protein-coding and lncRNA transcripts. Interestingly, a significant proportion of short RNAs derived from full-length viral genomes also aligned to various hg38 sequences, suggesting opportunities to investigate regulatory roles of svRNAs during infection. Further characterization of the small RNA landscape of both viral and host genomes is clearly warranted to improve our understanding of molecular events related to infection and to design more efficient strategies for therapeutic interventions as well as early diagnosis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.27.522023v1" target="_blank">Viral and host small RNA transcriptome analysis of SARS-CoV-1 and SARS-CoV-2-infected human cells reveals novel viral short RNAs.</a>
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</div></li>
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<li><strong>SCIP: A self-paced, community-based summer coding program creates community and increases coding confidence</strong> -
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<div>
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In 2020, many students lost summer opportunities due to the COVID-19 pandemic. We wanted to offer students an opportunity to learn computational skills and be part of a community while stuck at home. Because the pandemic created an unexpected research and academic situation, it was unclear how to best support students to learn and build community online. We used lessons learned from literature and our own experience to design, run and test an online program for students called the Science Coding Immersion Program (SCIP). In our program, students worked in teams for 8 hours a week, with one participant as the team leader and Zoom host. Teams worked on an online R or Python class at their own pace with support on Slack from the organizing team. For motivation and career advice, we hosted a weekly webinar with guest speakers. We used pre- and post-program surveys to determine how different aspects of the program impacted students. We were able to recruit a large and diverse group of participants who were happy with the program, found community in their team, and improved their coding confidence. We hope that our work will inspire others to start their own version of SCIP.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.27.521952v1" target="_blank">SCIP: A self-paced, community-based summer coding program creates community and increases coding confidence</a>
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</div></li>
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<li><strong>A second update on mapping the human genetic architecture of COVID-19</strong> -
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Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release. The increased number of candidate genes at the identified loci helped to map three major biological pathways involved in susceptibility and severity: viral entry, airway defense in mucus, and type I interferon.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.24.22283874v1" target="_blank">A second update on mapping the human genetic architecture of COVID-19</a>
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</div></li>
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<li><strong>Study COVID-19 Severity of Patients Admitted to Emergency Room (ER) with Chest X-ray Images</strong> -
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Abstract. We have conducted a study of the COVID-19 severity with the chest x-ray images, a private dataset collected from our collaborator St Bernards Medical Center. The dataset is comprised of chest x-ray images from 1,550 patients who were admitted to emergency room (ER) and were all tested positive for COVID-19. Our study is focused on the following two questions: (1) To predict patients hospital staying duration, based on the chest x-ray image which was taken when the patient was admitted to the ER. The length of stay ranged from zero hours to 95 days in the hospital and followed a power law distribution. Based on our testing results, it is hard for the prediction models to detect strong signal from the chest x-ray images. No model was able to perform better than a trivial most-frequent classifier. However, each model was able to outperform the most-frequent classifier when the data was split evenly into four categories. This would suggest that there is signal in the images, and the performance may be further improved by the addition of clinical features as well as increasing the training set. (2) To predict if a patient is COVID-19 positive or not with the chest x-ray image. We also tested the generalizability of training a prediction model on chest x-ray images from one hospital and then testing the model on images captures from other sites. With our private dataset and the COVIDx dataset, the prediction model can achieve a high accuracy of 95.9%. However, for our hold-one-out study of the generalizability of the models trained on chest x-rays, we found that the model performance suffers due to a significant reduction in training samples of any class.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.25.22283942v1" target="_blank">Study COVID-19 Severity of Patients Admitted to Emergency Room (ER) with Chest X-ray Images</a>
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<li><strong>Literature analysis of the efficacy of COVID-19 vaccinations</strong> -
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The COVID-19 pandemic is the largest epidemic of the 21st century so far. Over 650 million people have already been infected with the SARS-CoV-2 virus. One of the ways to stop this pandemic, is to vaccinate the population and gain herd immunity. Many different vaccines are being used around the world, with differing efficacy. This review summarizes the 79 publications on the efficacy of the currently existing COVID-19 vaccines. It shows that there are eleven vaccines that have efficacy data published in a PubMed-indexed scientific journal. Most research has been done on the Pfizer/BioNTech BNT162B2 vaccine, and the eleven vaccines generally have a high efficacy in preventing illness. The Pfizer (86%-100%), Moderna (93.2%-94.1%), Sputnik-V (91.6%) and Novavax (~90%) vaccines show the highest efficacy, followed by the Sinovac (83.5%), QazCovid-in 82%) and Covaxin (77.8%) vaccines. The Oxford/AstraZeneca (69% - 81.5%) and Johnson & Johnson (66%) vaccines have lower efficacy in preventing illness. This overview also shows efficacies other than in preventing illness (e.g. asymptomatic, severe illness, hospitalization, death) in some cases. The results also show that the vaccines have specific effects on specific age groups (e.g. adolescents, adults, elderly) and people with diseases (e.g. leukemia, other cancers, HIV). Future research in this area will mostly focus on vaccine efficacy on specific strains of the SARS-CoV-2 virus (such as the Omicron variant) as well as the efficacy of booster vaccinations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.24.22283835v1" target="_blank">Literature analysis of the efficacy of COVID-19 vaccinations</a>
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<li><strong>A Usability Evaluation of YouDiagnose: Artificial Intelligence Powered Physician Consultation</strong> -
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The COVID-19 Pandemic has resulted in a forced transition to telemedicine, where history-taking and clinical assessments are performed remotely during video or telephonic consultations. While telemedicine has added to safety and social distancing during the pandemic, the manual and resource-intense pro-cess of telephonic and video consultations has not helped to ease the patient backlog, rather has added to this snowballing issue. This paper describes about YouDiagnose pre-consultation exercise that automates patient triage and clinical assessment using artificial intelligence technologies delivered through either a Smart Questionnaire or Chatbot. A usability evaluation was conducted with participants from the Patient and Public Involvement and Engagement Senate (PIES) of the Innovation Agency (an Academic Health Science Net-work) Qualitative feedback was obtained from the participants on both modalities and quantitative feedback in the form of the System Usability Scale (SUS), comparing the usability of both interaction modalities. The SUS scores were analysed using the Adjective Rating Scale that revealed the Smart Questionnaire had Good Usability compared to OK Usability of the Chatbot. The results shows the user experience and untapped potential of process automation and artificial intelligence in clinical services.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.20.22283710v1" target="_blank">A Usability Evaluation of YouDiagnose: Artificial Intelligence Powered Physician Consultation</a>
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<li><strong>The response to BTN62b2 booster doses demonstrates that serum antibodies do not predict the establishment of immune B-cell memory in common variable immune deficiencies</strong> -
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In patients with common variable immune deficiencies, primary vaccination followed by two booster doses is recommended for protection against COVID-19. Seroconversion has been shown in 60% of patients. We have no information on whether serum antibodies reflect the generation of durable immune memory. In a longitudinal study on 47 common variable immune deficiencies patients who received the third and fourth vaccine dose, we show that the measurement of specific antibodies is not sufficient to predict the establishment of immune memory and the ability to respond to antigen re-exposure. Our results indicate that the combination of antibodies and memory B cells responses represents a more reliable read-out of vaccine immune efficacy in vulnerable patients. This analysis may not only identify individuals remaining unprotected after vaccination and unable to respond to additional booster doses, but also address the search for the underlying immune defect and suggest patient-tailored management strategies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.24.22283775v1" target="_blank">The response to BTN62b2 booster doses demonstrates that serum antibodies do not predict the establishment of immune B-cell memory in common variable immune deficiencies</a>
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<li><strong>Techniques for Developing Reliable Machine Learning Classifiers Applied to Understanding and Predicting Protein:Protein Interaction Hot Spots</strong> -
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With machine learning now transforming the sciences, successful prediction of biological structure or activity is mainly limited by the extent and quality of data available for training, the astute choice of features for prediction, and thorough assessment of the robustness of prediction on a variety of new cases. Here we address these issues while developing and sharing protocols to build a robust dataset and rigorously compare several predictive classifiers using the open-source Python machine learning library, scikit-learn. We show how to evaluate whether enough data has been used for training and whether the classifier has been overfit to training data. The most telling experiment is 500-fold repartitioning of the training and test sets, followed by prediction, which gives a good indication of whether a classifier performs consistently well on different datasets. An intuitive method is used to quantify which features are most important for correct prediction. The resulting well-trained classifier, hotspotter, can robustly predict the small subset of amino acid residues on the surface of a protein that are energetically most important for binding a protein partner: the interaction hot spots. Hotspotter has been trained and tested here on a curated dataset assembled from 1,046 non-redundant alanine scanning mutation sites with experimentally measured change in binding free energy values from 97 different protein complexes; this dataset is available to download. The accessible surface area of the wild-type residue at a given site and its degree of evolutionary conservation proved the most important features to identify hot spots. A variant classifier was trained and validated for proteins where only the amino acid sequence is available, augmented by secondary structure assignment. This version of hotspotter requiring fewer features is almost as robust as the structure-based classifier. Application to the ACE2 receptor, which mediates COVID-19 virus entry into human cells, identified the critical hot spot triad of ACE2 residues at the center of the small interface with the CoV-2 spike protein. Hotspotter results can be used to guide the strategic design of protein interfaces and ligands and also to identify likely interfacial residues for protein:protein docking.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.26.521948v1" target="_blank">Techniques for Developing Reliable Machine Learning Classifiers Applied to Understanding and Predicting Protein:Protein Interaction Hot Spots</a>
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<li><strong>Evaluation of the molecular diversity of Brazilian strains of the B.1.1 variant of SARS-CoV-2 used in vaccines</strong> -
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In this work, 28 sequences with 57,570 sites of the B.1.1 variant of SARS-CoV-2, from Brazilian states, were used. All sequences (publicly available on the National Center for Biotechnology Information platform (NCBI)) were aligned with Mega X software and all gaps, ambiguous sites and lost data were extracted, resulting in a region in a segment with 8,799 polymorphic (15.2% of the total) that were analyzed for their molecular diversity, FST, demographic and spatial expansion. Phylogenetic relationships of ancestry revealed the absence of genetically distinct subgroups, which was corroborated by the low value of FST found (15.38%). The low degree of polymorphism found among these samples, corroborated by the almost non-existent genetic distance, helped or established the absence of a genetic structuring pattern, demonstrating a satisfactory pattern of response to vaccines, since all the sequences analyzed were part of the Brazilian strains of variant B.1.1 of SARS-CoV-2 used in vaccines.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.23.521847v1" target="_blank">Evaluation of the molecular diversity of Brazilian strains of the B.1.1 variant of SARS-CoV-2 used in vaccines</a>
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<li><strong>Tissue protective role of Ganetespib in SARS-CoV-2-infected Syrian golden hamsters</strong> -
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The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are therefore urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyper-inflammatory state generated upon infection, at reducing lung tissue pathology and endothelial damages, along with viral replication. Previous research has pointed a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses. In this study, we analyzed the effects of the potent HSP90 inhibitor Ganetespib in vitro on alveolar epithelial cells and alveolar macrophages to characterize its effects on cell activation and viral replication. Additionally, to evaluate its efficacy in controlling systemic inflammation and the viral burden after infection in vivo, a Syrian hamster model was used. In vitro, Ganetespib reduced viral replication on AECs in a dose-dependent manner and lowered significantly the expression of pro-inflammatory genes, in both AECs and alveolar macrophages. In vivo, administration of Ganetespib led to an overall improvement of the clinical condition of infected animals, with decreased systemic inflammation, reduced edema formation and lung tissue pathology. Altogether, we show that Ganetespib could be a potential medicine to treat moderate and severe cases of COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.27.521979v1" target="_blank">Tissue protective role of Ganetespib in SARS-CoV-2-infected Syrian golden hamsters</a>
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<li><strong>Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants</strong> -
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In late 2022, the SARS-CoV-2 Omicron subvariants have highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged by recombination of two co-circulating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022 around India. In vitro experiments revealed that XBB is the most profoundly resistant variant to BA.2/5 breakthrough infection sera ever and is more fusogenic than BA.2.75. Notably, the recombination breakpoint is located in the receptor-binding domain of spike, and each region of recombined spike conferred immune evasion and augmented fusogenicity to the XBB spike. Finally, the intrinsic pathogenicity of XBB in hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provided evidence suggesting that XBB is the first documented SARS-CoV-2 variant increasing its fitness through recombination rather than single mutations.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.27.521986v1" target="_blank">Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants</a>
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<li><strong>An alpaca-derived nanobody neutralizes the SARS-CoV-2 omicron variant</strong> -
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The SARS-CoV2 Omicron variant sub-lineages spread rapidly through the world, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for anti-SARS-CoV-2 agents that are effective against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production and potential for delivery via inhalation. Here, we characterize the RBD-specific nanobody W25, which we previously isolated from an alpaca, and show superior neutralization activity towards Omicron lineage BA.1 in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike surface glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. Furthermore, we show that W25 also binds the spike protein from the emerging, more infectious Omicron BA.2 lineage with picomolar affinity. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse prioritization of W25 for further clinical development.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.27.521990v1" target="_blank">An alpaca-derived nanobody neutralizes the SARS-CoV-2 omicron variant</a>
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<li><strong>ESCRT recruitment to mRNA-encoded SARS-CoV-2 spike induces virus-like particles and enhanced antibody responses</strong> -
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Prime-boost regimens for COVID-19 vaccines elicit poor antibody responses against Omicron-based variants and employ frequent boosters to maintain antibody levels. We present a natural infection-mimicking technology that combines features of mRNA- and protein nanoparticle-based vaccines through encoding self-assembling enveloped virus-like particles (eVLPs). eVLP assembly is achieved by inserting an ESCRT- and ALIX-binding region (EABR) into the SARS-CoV-2 spike cytoplasmic tail, which recruits ESCRT proteins to induce eVLP budding from cells. Purified spike-EABR eVLPs presented densely-arrayed spikes and elicited potent antibody responses in mice. Two immunizations with mRNA-LNP encoding spike-EABR elicited potent CD8+ T-cell responses and superior neutralizing antibody responses against original and variant SARS-CoV-2 compared to conventional spike-encoding mRNA-LNP and purified spike-EABR eVLPs, improving neutralizing titers >10-fold against Omicron-based variants for three months post-boost. Thus, EABR technology enhances potency and breadth of vaccine-induced responses through antigen presentation on cell surfaces and eVLPs, enabling longer-lasting protection against SARS-CoV-2 and other viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.26.521940v1" target="_blank">ESCRT recruitment to mRNA-encoded SARS-CoV-2 spike induces virus-like particles and enhanced antibody responses</a>
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<li><strong>Neuroendocrine involvement and retinoid signaling disorder in COVID-19: A different perspective on neuroendocrine involvement, menstrual irregularities and reproductive dysfunctions in COVID-19</strong> -
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Despite the intense work of researchers since the beginning of the pandemic, the pathogenesis of COVID-19 is not yet understood. Accordingly, the mechanism behind menstrual irregularities, abnormal uterine bleeding, abortions and reproductive problems in women has not been clearly clarified. Current information and a broad analysis of the literature suggest that retinol depletion and retinoid signaling defect may underlie the gynecological and reproductive problems seen in COVID-19. Retinol depletion and retinoid signaling disorder seen in COVID-19 can clearly explain the involvement in endocrine organs such as thyroid, pancreas and adrenal glands, apart from the disorders seen in the female genital system. It is known that SARS-CoV-2 causes chemosensory receptor disorders and exerts its pathogenic effects through these mechanisms. The relatively low expression of ACE2 receptors in the brain and endocrine organs, which are responsible for the invasion of SARS-CoV2 into host cells in COVID-19, is insufficient to explain the severe involvement of these organs. Systemic involvement and multi-organ damage in COVID-19 also suggest that the pathogenetic disorder in COVID-19 develops through multiple receptors and signaling pathways. As a result of impaired retinoid activity in neuroendocrine and genital organs in COVID-19, GPCR and STRA6 receptor synthesis and function are also impaired. Likewise, the synthesis of GPCR and STRA6 receptors occurs depending on retinoid activity. Retinoid activity and its associated STRA6 and GPCR receptors are densely located in the limbic system, which is the center of emotional activity in the brain, and in the thalamus, hypothalamus, pituitary gland and reproductive organs, which is the center of neuroendocrine regulation. This suggests that the excessive uterine bleeding, endocrine system and reproductive disorders in COVID-19 are caused by the deterioration of retinoid activity in this region. Likewise, the high expression of GPCRS and GnRH receptors in the brain and endocrine organs is in parallel with the neuroendocrine and genital organ involvement of COVID-19. The retinoid signaling defect, associated signaling pathways and receptors illuminate the complex mechanism of neuroendocrine involvement and peripheral organ involvement in COVID-19.
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🖺 Full Text HTML: <a href="https://osf.io/rkyfg/" target="_blank">Neuroendocrine involvement and retinoid signaling disorder in COVID-19: A different perspective on neuroendocrine involvement, menstrual irregularities and reproductive dysfunctions in COVID-19</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>101-PGC-005 for the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: 101-PGC-005; Drug: Dexamethasone<br/><b>Sponsor</b>: 101 Therapeutics<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 Clinical Study to Assess Preliminary Efficacy, Safety and Tolerability of HH-120 Nasal Spray in COVID-19 Patients</strong> - <b>Condition</b>: Coronavirus Disease 2019(COVID-19)<br/><b>Intervention</b>: Biological: HH-120 Nasal Spray<br/><b>Sponsor</b>: Beijing Ditan Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Booster Study in Healthy Adults in Australia</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Bivalent Moderna; Biological: Novavax<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<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>Effect of N-Acetylcysteine on Neutrophil Lymphocyte Ratio And Length of Stay In COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: N-acetyl cysteine<br/><b>Sponsor</b>: Universitas Sebelas Maret<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>Efficacy and Safety of Anti-COVID-19 Antibody SA58 Nasal Spray to Prevent Infection in High-risk Populations</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: SA58 Nasal Spray<br/><b>Sponsor</b>: Sinovac Life Sciences Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Ambervin® and Standard Therapy in Hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate intramuscularly; Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate inhaled; Drug: Standard of care<br/><b>Sponsor</b>: Promomed, LLC<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety of COVID-19 Vaccine as a Booster Vaccination in Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant SARS-CoV-2 Vaccine (CHO Cell) LYB001; Biological: ZF2001<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech 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>Immunogenicity and Safety of COVID-19 Vaccine in Population Aged 18 Years and Above（Negative Antibody Against COVID-19）</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: One dose group; Biological: Two doses group; Biological: Aged 18-59 years; Biological: Aged 60 years old and above<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech 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>Study of GST-HG171/Ritonavir Compared With Placebo in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: GST-HG171/Ritonavir; Drug: Placebo<br/><b>Sponsor</b>: Fujian Akeylink Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A PhaseⅡ Study to Evaluate the Safety & Immunogenicity of SARS-CoV-2 Alpha/Beta/Delta/Omicron Variants COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: SCTV01E; Biological: Placebo (normal saline)<br/><b>Sponsor</b>: Sinocelltech 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>The COPE Study: Pilot Intervention to Improve Symptom Self-management and Coping in Adults With Post COVID-19</strong> - <b>Conditions</b>: Post COVID-19 Condition; Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: 6-Week Self-Management Group<br/><b>Sponsor</b>: University of Washington<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>ICBT for Psychological Symptoms Related to the COVID-19 Pandemic Remaining After Societal Opening</strong> - <b>Condition</b>: Depression and Anxiety Symptoms Related to the COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Internet-based Cognitive Behavioral Therapy<br/><b>Sponsor</b>: Linkoeping University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ARVAC - A New Recombinant Coronavirus Disease 2019 (COVID-19) Vaccine</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Intervention</b>: Biological: ARVAC-CG vaccine (recombinant protein vaccine against SARS-CoV-2)<br/><b>Sponsors</b>: Laboratorio Pablo Cassara S.R.L.; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina<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>Graphene Photothermal Adjuvant Therapy for Mild Corona Virus Disease 2019: A Prospective Randomized Controlled Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Graphene spectrum light wave therapy room<br/><b>Sponsors</b>: Southeast University, China; Hohhot First Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The KIN-FAST Trial (KIN001 For Accelerated Symptoms Termination) in Non Hospitalized Patients Infected With SARS-CoV-2</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: KIN001; Drug: KIN001-Placebo<br/><b>Sponsor</b>: Kinarus AG<br/><b>Recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline</strong> - The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology…</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>Performance and correlation of ten commercial immunoassays for the detection of SARS-CoV-2 antibodies</strong> - Accurate immunoassays with a good correlation to neutralizing antibodies are required to support SARS-CoV-2 diagnosis, management, vaccine deployment, and epidemiological investigation. We conducted a study to evaluate the performance and correlation of the surrogate virus neutralization test (sVNT) and other commercial immunoassays. We tested 107 sera of COVID-19 confirmed cases from three different time points, 58 confirmed non-COVID-19 sera, and 52 sera collected before the pandemic with two…</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 accessory proteins ORF7a and ORF3a use distinct mechanisms to down-regulate MHC-I surface expression</strong> - Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small-protein β(2)-microglobulin (β(2)m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells, these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those…</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>Carotenoids as potential inhibitors of TNFα in COVID-19 treatment</strong> - Tumor necrosis factor-alpha (TNF-α) is a multifunctional pro-inflammatory cytokine, responsible for autoimmune and inflammatory disorders. In COVID-19 patients, increased TNF-α concentration may provoke inflammatory cascade and induce the initiation of cytokine storm that may result in fatal pneumonia and acute respiratory distress syndrome (ADRS). Hence, TNFα is assumed to be a promising drug target against cytokine storm in COVID-19 patients. In the present study, we focused on finding novel…</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>Infectivity of pseudotyped SARS-CoV-2 variants of concern in different human cell types and inhibitory effects of recombinant spike protein and entry-related cellular factors</strong> - Since the report of the first COVID-19 case in 2019, SARS-CoV-2 variants of concern (VOCs) have continued to emerge, manifesting diverse infectivity, evasion of host immunity and pathology. While ACE2 is the predominant receptor of SARS-CoV-2, TMPRSS2, Kim-1, NRP-1, CD147, furin, CD209L and CD26 have also been implicated as viral entry-related cofactors. To understand the variations in infectivity and pathogenesis of VOCs, we conducted infection analysis in human cells from different organ…</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 prediction of SARS-CoV-2 main protease inhibition with filtering by position of ligand</strong> - The paper analyzes a set of equations that adequately predict the IC50 value for SARS-CoV-2 main protease inhibitors. The training set was obtained using filtering by criteria independent of prediction of target value. It included 76 compounds, and the test set included nine compounds. We used the values of energy contributions obtained in the calculation of the change of the free energy of complex by MMGBSA method and a number of characteristics of the physical and chemical properties of 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>Impacts of video communication on psychological well-being and cosmetic surgery acceptance</strong> - Video communication via platforms such as Zoom has been routinely used as a communication tool during the COVID-19 pandemic. Scientific evidence has suggested that constant video communication can have detrimental consequences such as “Zoom fatigue”, inhibiting collaboration, and new information exchange. The current study focuses on the effects of using video communication technology on self-esteem, affect, and image perception under the framework of objective self-awareness (OSA). We…</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 new intracellular targeting motif in the cytoplasmic tail of the spike protein may act as a target to inhibit SARS-CoV-2 assembly</strong> - Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a threat to global public health, underscoring the urgent need for the development of preventive and therapeutic measures. The spike (S) protein of SARS-CoV-2, which mediates receptor binding and subsequent membrane fusion to promote viral entry, is a major target for current drug development and vaccine design. The S protein comprises a large N-terminal extracellular domain, a transmembrane domain, and a short…</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>Regulatory role of endoplasmic reticulum resident chaperone protein ERp29 in anti-murine β-coronavirus host cell response</strong> - Gap junctional intercellular communication (GJIC) involving astrocytes is important for proper CNS homeostasis. As determined in our previous studies, trafficking of the predominant astrocyte GJ protein, Connexin43 (Cx43), is disrupted in response to infection with a neurotropic murine β-coronavirus (MHV-A59). However, how host factors are involved in Cx43 trafficking and the infection response is not clear. Here, we show that Cx43 retention due to MHV-A59 infection was associated with increased…</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>Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial</strong> - CONCLUSION: Our interim analysis provides proof-of-concept data on CVC for COVID-19 patients as intervention to inhibit CCR2/CCR5. Further studies are warranted to assess its clinical efficacy.</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>Mammalian hybrid prophagophore is a precursor to autophagosomes</strong> - SUMMARYThe precursors to mammalian autophagosomes originate from pre-existing membranes contributed by a number of sources, and subsequently enlarge through intermembrane lipid transfer, then close to sequester the cargo, and merge with lysosomes to degrade the cargo. Using cellular and in vitro membrane fusion analyses coupled with proteomic and biochemical studies we show that autophagosomes are formed from a hybrid membrane compartment referred to as a prophagophore or HyPAS (hybrid…</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>Booster shot of inactivated SARS-CoV-2 vaccine induces potent immune responses in people living with HIV</strong> - CONCLUSIONS: PLWH receiving booster shot of inactivated vaccines generate higher antibody responses than the second dose, but lower than that in HCs. Decreased anti-BA.4/5 responses than that of WT impede the protective effect of the third dose on Omicron prevalence. This article is protected by copyright. All rights reserved.</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 novel poly (4-methyl-1-pentene)/polypropylene (PMP/PP) thin film composite (TFC) artificial lung membrane for enhanced gas transport and excellent hemo-compatibility</strong> - Extracorporeal membrane oxygenation is a technique that provides short-term supports to the heart and lungs. It removes CO(2) from the blood and provides enough oxygen, which is a huge help in the fight against COVID-19. As the key component, the artificial lung membranes have evolved in three generations including silicon, polypropylene and poly (4-methyl-1-pentene). Herein, we for the first time design and fabricate a novel poly (4-methyl-1-pentene)/polypropylene (PMP/PP) thin film composite…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Human miRNA Biomarkers Targeting the SARS-CoV-2 Genome</strong> - SARS-CoV-2 poses a great challenge toward mankind, majorly due to its evolution and frequently occurring variants. On the other hand, in human hosts, microRNA (miRNA) plays a vital role in replication and propagation during a viral infection and can control the biological processes. This may be essential for the progression of viral infection. Moreover, human miRNAs can play a therapeutic role in treatment of different viral diseases by binding to the target sites of the virus genome, thereby…</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>Dual-Reporter System for Real-Time Monitoring of SARS-CoV-2 Main Protease Activity in Live Cells Enables Identification of an Allosteric Inhibition Path</strong> - The SARS-CoV-2 pandemic is an ongoing threat to global health, and the continuing emergence of contagious variants highlights the urgent need for additional antiviral therapy to attenuate COVID-19 disease. The SARS-CoV-2 main protease (3CL^(pro)) presents an attractive target for such therapy due to its high sequence conservation and key role in the viral life cycle. In this study, we designed a fluorescent-luminescent cell-based reporter for the detection and quantification of 3CL^(pro)…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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