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180 lines
49 KiB
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<title>24 October, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 synergistically enhances antibody evasion and ACE2 binding</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants like EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. L455F and F456L evade Class 1 NAbs, reducing the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. The perturbed receptor-binding mode leads to the exceptional ACE2 binding and NAb evasion, as revealed by structural analyses. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.30.555211v2" target="_blank">Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 synergistically enhances antibody evasion and ACE2 binding</a>
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<li><strong>The impact of spatial connectivity on NPIs effectiveness</strong> -
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Background. France implemented a combination of non-pharmaceutical interventions (NPIs) to manage the COVID-19 pandemic between September 2020 and June 2021. These included a lockdown in the fall 2020 - the second since the start of the pandemic - to counteract the second wave, followed by a long period of nighttime curfew, and by a third lockdown in the spring 2021 against the Alpha wave. Interventions have so far been evaluated in isolation, neglecting the spatial connectivity between regions through mobility that may impact NPI effectiveness. Methods. Focusing on September 2020 - June 2021, we developed a regionally-based epidemic metapopulation model informed by observed mobility fluxes from daily mobile phone data and fitted the model to regional hospital admissions. The model integrated data on vaccination and variants spread. Scenarios were designed to assess the impact of the Alpha variant, characterized by increased transmissibility and risk of hospitalization, of the vaccination campaign and alternative policy decisions. Results. The spatial model better captured the heterogeneity observed in the regional dynamics, compared to models neglecting inter-regional mobility. The third lockdown was similarly effective to the second lockdown after discounting for immunity, Alpha, and seasonality (51% vs 52% median regional reduction in the reproductive number R0, respectively). The 6pm nighttime curfew with bars and restaurants closed, implemented in January 2021, substantially reduced COVID-19 transmission. It initially led to 49% median regional reduction of R0, decreasing to 43% reduction by March 2021. In absence of vaccination, implemented interventions would have been insufficient against the Alpha wave. Counterfactual scenarios proposing a sequence of lockdowns in a stop-and-go fashion would have reduced hospitalizations and restriction days for low enough thresholds triggering and lifting restrictions. Conclusions. Spatial connectivity induced by mobility impacted the effectiveness of interventions especially in regions with higher mobility rates. Early evening curfew with gastronomy sector closed allowed authorities to delay the third wave. Stop-and-go lockdowns could have substantially lowered both healthcare and societal burdens if implemented early enough, compared to the observed application of lockdown-curfew-lockdown, but likely at the expense of several labor sectors. These findings contribute to characterize the effectiveness of implemented strategies and improve pandemic preparedness. Keywords. COVID-19, NPIs, modeling, curfew, restrictions.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.23.23297403v1" target="_blank">The impact of spatial connectivity on NPIs effectiveness</a>
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<li><strong>In vivo affinity maturation of murine B cells reprogrammed to express human antibodies</strong> -
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<div>
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CRISPR-edited murine B cells engineered to express human antibody variable chains proliferate, class switch, and secrete these antibodies in vaccinated mice. However, current strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that recombined murine heavy- and kappa-variable genes can be directly and simultaneously overwritten, using Cas12a-mediated cuts at their 3'-most J segments and 5' homology arms complementary to distal V segments. Cells edited in this way to express the HIV-1 broadly neutralizing antibodies 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated recipient mice. 10-1074 variants isolated from these mice bound and neutralized HIV-1 envelope glycoprotein more efficiently than wild-type 10-1074 while maintaining or improving its already low polyreactivity and long in vivo half-life. We further validated this approach by generating substantially broader and more potent variants of the anti-SARS-CoV-2 antibodies ZCB11 and S309. Thus, B cells edited at their native loci affinity mature, facilitating development of broad, potent, and bioavailable antibodies and expanding the potential applications of engineered B cells.
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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/10.1101/2023.10.20.563154v1" target="_blank">In vivo affinity maturation of murine B cells reprogrammed to express human antibodies</a>
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<li><strong>Assessing nanobody interaction with SARS-CoV-2 Nsp9</strong> -
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The interaction between SARS-CoV-2 non-structural protein Nsp9 and the nanobody 2NSP90 was investigated by NMR spectroscopy using the paramagnetic perturbation methodology PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation). The Nsp9 monomer is an essential component of the replication and transcription complex (RTC) that reproduces the viral gRNA for subsequent propagation. Therefore preventing Nsp9 recruitment in RTC would represent an efficient antiviral strategy that could be applied to different coronaviruses, given the Nsp9 relative invariance. The NMR results were consistent with a previous characterization suggesting a 4:4 Nsp9-to-nanobody stoichiometry with the occurrence of two epitope pairs on each of the Nsp9 units that establish the inter-dimer contacts of Nsp9 tetramer. The oligomerization state of Nsp9 was also analyzed by molecular dynamics simulations and both dimers and tetramers resulted plausible. However a different distribution of the mapped epitopes on the tetramer surface with respect to the former 4:4 complex could also be possible, as well as different stoichiometries of the Nsp9-nanobody assemblies such as the 2:2 stoichiometry suggested by the recent crystal structure of the Nsp9 complex with 2NSP23 (PDB ID: 8dqu), a nanobody exhibiting essentially the same affinity as 2NSP90. The experimental NMR evidence, however, ruled out the occurrence in liquid state of the relevant Nsp9 conformational change observed in the same crystal structure.
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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/10.1101/2023.10.20.563308v1" target="_blank">Assessing nanobody interaction with SARS-CoV-2 Nsp9</a>
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<li><strong>Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages</strong> -
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Motivation: Charged amino acid residues on the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to influence its binding to different cell surface receptors, its non-specific electrostatic interactions with the environment, and its structural stability and conformation. It is therefore important to obtain a good understanding of amino acid mutations that affect the total charge on the spike protein which have arisen across different SARS-CoV-2 lineages during the course of the virus' evolution. Results: We analyse the change in the number of ionizable amino acids and the corresponding total charge on the spike proteins of almost 2000 SARS-CoV-2 lineages that have emerged over the span of the pandemic. Our results show that the previously observed trend toward an increase in the positive charge on the spike protein of SARS-CoV-2 variants of concern has essentially stopped with the emergence of the early omicron variants. Furthermore, recently emerged lineages show a greater diversity in terms of their composition of ionizable amino acids. We also demonstrate that the patterns of change in the number of ionizable amino acids on the spike protein are characteristic of related lineages within the broader clade division of the SARS-CoV-2 phylogenetic tree. Due to the ubiquity of electrostatic interactions in the biological environment, our findings are relevant for a broad range of studies dealing with the structural stability of SARS-CoV-2 and its interactions with the environment. Availability: The data underlying the article are available in the online Supplementary Material.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.21.563433v1" target="_blank">Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages</a>
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<li><strong>Screening Peptide Drug Candidates to Neutralize Whole Viral Agents : A Case study with SARS-CoV-2 Virus</strong> -
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Covid19 pandemic revealed the reality for the need of therapeutic and pharmaceutical molecule development in a short time with different approaches. Although the enhancement of immunological memory by vaccination was the quicker and robust strategy, still medication is required for immediate treatment for a patient. For this purpose, one of the approaches is developing new therapeutic molecule development like peptide-based drugs. Also, peptides can be used developing other molecules like nanobodies. Here, M13 phage display library was used for selecting SARS-CoV-2 interacting peptides for developing a neutralizing molecule for further use. Biopanning was applied with four iterative cycles to select phages displaying different 12-amino acid-long peptides. Then, the M13 phage genomic region where peptide sequences expressed were analyzed and sequences were obtained. Randomly selected peptide sequences were synthesized by solid-state peptide synthesis method. These peptides were analyzed by quartz crystal microbalance method in terms or peptide interaction capacity with specifically wild-type S protein. Next, QCM data was further validated by enzyme-linked immunosorbent assay (ELISA) in order to check peptides according to their neutralizing capacity rather than binding to S1 protein. The results showed that, phage display served an opportunity for selecting peptides which can be used and developed further as pharmaceutical molecules. More specifically, scpep3, scpep8 and scpep10 had both binding and neutralizing capacity for S1 protein as a candidate for therapeutic molecule.
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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/10.1101/2023.10.22.563490v1" target="_blank">Screening Peptide Drug Candidates to Neutralize Whole Viral Agents : A Case study with SARS-CoV-2 Virus</a>
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<li><strong>A bioactive peptide from the pearl has dual roles in resisting SARS-CoV-2 infection and its complications</strong> -
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Angiotensin-converting enzyme 2 (ACE2) is a critical receptor for the entry of the SARS-CoV-2 virus into cells. Moreover, a decrease in ACE2 level and its activity due to SARS-CoV-2 infection is considered a crucial reason for the development of Covid-19-associated complications. Here, we report a bioactive peptide derived from the seawater pearl oyster Pinctada fucata, named SCOL polypeptide, which binds strongly to ACE2 and effectively inhibits 65% of the binding of the SARS-CoV-2 S protein to ACE2; thus, this peptide can be used as a blocker to enable cells to resist SARS-CoV-2 infection. The SCOL polypeptide also increases ACE2 enzyme activity by 3.76 times. Previous studies have shown that ACE2 deficiency is associated with inflammation, pain, cardiovascular diseases, insulin resistance, and nervous system injury. Therefore, the SCOL polypeptide can be used to treat or alleviate complications such as lung inflammation, pain, diabetes, cardiovascular diseases, and loss of taste or smell caused by SARS-CoV-2 infection. Thus, the SCOL polypeptide can play a dual role in resisting SARS-CoV-2 infection.
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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/10.1101/2023.10.23.563427v1" target="_blank">A bioactive peptide from the pearl has dual roles in resisting SARS-CoV-2 infection and its complications</a>
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<li><strong>ASSESSING SYSTEM PERFORMANCE OF MATERNAL AND CHILD HEALTH CARE DURING COVID-19 PANDEMIC IN COMMUNITY HEALTH CENTER- COMORO DILI TIMOR-LESTE.</strong> -
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ABSTRACT “Purpose/ Introduction: Recent Evidences reveal that COVID-19 pandemic caused MCH services interruption world-wide. In Timor-Leste, MCH services is one of service priorities and delivers through 3 tiers of health structures consists of hospitals, CHCs, and HPs. The Country (Timor-Leste) identified its first case of COVID-19 in March and by April 2020, it was lockdown and stringent actions were enforced. Nuring the pandemic COVID-19, the MOH health structures and facilities continued delivers essential health services. However, the strict lockdown and mandatory stay home order had negatively impacted the health system capacities. This study to thoroughly assess the disruption of System Components of MCH Services by interviewed frontline HCWs from Comoro -CHC, in Dili-Timor-Leste. Patients and Methods: The cross-sectional approach with quantitative descriptive method was employed for this study. We employed a modified who six building blocks (service delivery, human resources, drugs and consumables, ICT, Financing, Stewardship) to assess system disruption of MCH services in Comoro CHC due to COVID-19 Pandemic. Sample of 99 participants consisted of medical doctors, midwives, nurses who work at MCH unit pharmacy technicians, unit laboratory technicians, a structured questionnaire was utilized and data analysis was used SPSS. Result: The findings reveal the disruption of all 6 system blocks from MCH services in Comoro-CHC, Dili, Timor-Leste due to COVID-19 Pandemic. Except leadership, statistical tests reveal statistically significant association between interruption of five blocks from MCH services. The service delivery, human resources, drugs and consumables, ICT, Financing, Stewardship. Conclusion: COVID-19 Pandemic Caused disruption of all six health system blocks of MCH Services in Comoro, CHC. For future pandemic preparation plan, the attention must be given to all six-health system blocks to guarantee continue delivery of MCH care in CHC Comoro, Dili, Timor-Leste and a primary health care facility and other similar settings.Keywords: Performance, Maternal, Child, Health, System, COVID-19”
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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/10.1101/2023.10.23.23297388v1" target="_blank">ASSESSING SYSTEM PERFORMANCE OF MATERNAL AND CHILD HEALTH CARE DURING COVID-19 PANDEMIC IN COMMUNITY HEALTH CENTER- COMORO DILI TIMOR-LESTE.</a>
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<li><strong>Proportion of cancer cases and deaths attributable to potentially modifiable risk factors in Peru prior to the COVID-19 pandemic</strong> -
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OBJECTIVE: To estimate the fraction of cancer cases and deaths attributable to potentially modifiable risk factors in Peru in 2018, prior to the COVID-19 pandemic. MATERIAL AND METHODS: An ecological study was carried out using the prevalence of exposure of the Peruvian population to modifiable risk factors for cancer, relative risk of each risk factor, and number of cancer cases and deaths in 2018 as inputs. We used the Parkin formula with a Montecarlo statistical simulation model to calculate the population attributable fraction (PAF) and confidence intervals. The number of new cancer cases and deaths attributable to each risk factor was calculated by multiplying the number of cases and deaths in each sex by the PAF of each risk factor. RESULTS: 38.4% of new cases (34.4% in men and 41.8% in women) and 43.2% of deaths by cancer in Peru (43.1% in men and 43.2% in women) were attributable to modifiable risk factors. The number of cancers attributable was 25,591 (10,616 in men and 14,975 in women) and the number of deaths attributable to cancer was 14,922 (6,996 in men and 7,926 in women). The modifiable risk factors that caused a greater number of cases and deaths were HPV infection (4563 cases, 2410 deaths), current tobacco use (3387 cases, 2198 deaths), and Helicobacter pylori infection (2686 cases, 1874 deaths). The oncogenic infections made up the group of risk factors that presented a greater PAF (16.6% for cases, 19.1% for deaths) followed by other unhealthy lifestyle factors (14.1% for cases, 16.5% for deaths), tobacco (7.2% for cases, 7.3% for deaths) and ultraviolet radiation (0.5% for cases, 0.3% for deaths). CONCLUSION: Prior to the COVID-19 pandemic, a proportion of 38.4% of cancer cases and 43.2% of cancer deaths in Peru during 2018 were attributable to modifiable risk factors. Most preventable cancer cases and deaths are linked to oncogenic infections, primarily caused by HPV and Helicobacter pylori.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.22.23297358v1" target="_blank">Proportion of cancer cases and deaths attributable to potentially modifiable risk factors in Peru prior to the COVID-19 pandemic</a>
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<li><strong>COVision: Convolutional Neural Network for the Differentiation of COVID-19 from Common Pulmonary Conditions Using CT Scans</strong> -
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With the growing amount of COVID-19 cases, especially in developing countries with limited medical resources, it is essential to accurately and efficiently diagnose COVID-19. Due to characteristic ground-glass opacities (GGOs) and other types of lesions being present in both COVID-19 and other acute lung diseases, misdiagnosis occurs often: 26.6% of the time in manual interpretations of CT scans. Current deep-learning models can identify COVID-19 but cannot distinguish it from other common lung diseases like bacterial pneumonia. Concretely, COVision is a deep-learning model that can differentiate COVID-19 from other common lung diseases, with high specificity using CT scans and other clinical factors. COVision was designed to minimize overfitting and complexity by decreasing the number of hidden layers and trainable parameters while still achieving superior performance. Our model consists of two parts: the CNN which analyzes CT scans and the CFNN (clinical factors neural network) which analyzes clinical factors such as age, gender, etc. Using federated averaging, we ensembled our CNN with the CFNN to create a comprehensive diagnostic tool. After training, our CNN achieved an accuracy of 95.8% and our CFNN achieved an accuracy of 88.75% on a validation set. We found a statistical significance that COVision performs better than three independent radiologists with at least 10 years of experience, especially in differentiating COVID-19 from pneumonia. We analyzed our CNN activation maps through Grad-CAMs and found that lesions in COVID-19 presented peripherally, closer to the pleura, whereas pneumonia lesions presented centrally.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.22.23284880v3" target="_blank">COVision: Convolutional Neural Network for the Differentiation of COVID-19 from Common Pulmonary Conditions Using CT Scans</a>
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<li><strong>Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5’ untranslated region</strong> -
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One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) in their genomes. These conserved RNA structures are often essential for viral replication, transcription, or translation. In this report, we discovered and optimized a new type of coumarin derivatives, such as C30 and C34, which bind to a four-way RNA helix called SL5 in the 5’ UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a novel sequencing-based method namely cgSHAPE-seq, in which the acylating chemical probe was directed to crosslink with the 2’-OH groups of ribose at the ligand binding site. This crosslinked RNA could then create read-through mutations during reverse transcription (i.e., primer extension) at single-nucleotide resolution to uncover the acylation locations. cgSHAPE-seq unambiguously determined that a bulged G in SL5 was the primary binding site of C30 in the SARS-CoV-2 5’ UTR, which was validated through mutagenesis and in vitro binding experiments. C30 was further used as a warhead in RNA-degrading chimeras to reduce viral RNA expression levels. We demonstrated that replacing the acylating moiety in the cgSHAPE probe with ribonuclease L recruiter (RLR) moieties yielded RNA degraders active in the in vitro RNase L degradation assay and SARS-CoV-2 5’ UTR expressing cells. We further explored another RLR conjugation site on the E ring of C30/C34 and discovered improved RNA degradation activities in vitro and in cells. The optimized RNA-degrading chimera C64 inhibited live virus replication in lung epithelial carcinoma cells.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535453v2" target="_blank">Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5’ untranslated region</a>
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<li><strong>Quality of life, resources, and coping during the first weeks of the COVID-19 pandemic by people seeking psychological counselling before the pandemic</strong> -
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Objectives. This study aimed to understand the relationship between resource gains and losses, coping, and quality of life during the growth phase of the COVID-19 pandemic. Material and Methods. The Internet-based survey covered 353 individuals who had participated in a psychological support project operated by one of the non-governmental organisations in Lublin, Poland, in the 12 months prior to the outbreak of the pandemic. The questionnaire used in the study contained questions to collect sociodemographic data and psychometric scales to measure resource gains and losses (Conservation of Resources – Evaluation), quality of life (World Health Organization [WHO] Quality of Life-BREF), and strategies of coping with the pandemic situation (modified Brief Cope). Results. Higher global quality of life occurred with higher gains and minor losses, as well as with coping through planning, positive reframing, emotional support seeking, reduced substance use tendency, low self-blame, avoidance, and disengagement. Moreover, helplessness-based coping strategies were found to mediate both the relationship between resource gains and quality of life and between resource loss and quality of life. Conclusions. Factors that may reduce people’s quality of life during the COVID-19 pandemic are an increase in losses and limited gains, experienced over the six months preceding the pandemic, as well as not using active, meaning-oriented, and support-seeking coping strategies, but using avoidance behaviours instead. Coping strategies specific to people experiencing helplessness are a mediating mechanism between losses and limited gains of resources and quality of life.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/ryv8g/" target="_blank">Quality of life, resources, and coping during the first weeks of the COVID-19 pandemic by people seeking psychological counselling before the pandemic</a>
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<li><strong>Evaluation of the neutralising antibody response in human and hamster sera against SARS-CoV-2 variants up to and including BA.2.86 using an authentic virus neutralisation assay</strong> -
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New vaccines, therapeutics and immunity elicited by natural infection create evolutionary pressure on SARS-CoV-2 to evolve and adapt to evade vaccine-induced and infection-elicited immunity. Vaccine and therapeutics developers thus find themselves in an "arms race" with the virus. The ongoing assessment of emerging SARS-CoV-2 variants remains essential as the global community transitions from an emergency response to a long-term management plan. Here, we describe how an authentic virus neutralisation assay using low passage clinical virus isolates has been employed to monitor resistance of emerging virus variants to neutralising antibodies from humans and experimentally infected hamsters. Sera and plasma from people who received three doses of a vaccine as well as those who received a bivalent booster were assessed against SARS-CoV-2 variants, up to and including BA.2.86. Contemporary or recent virus variants showed substantial resistance to neutralisation by antibodies from those who had received three vaccines but were still effectively neutralised by antibodies from individuals who had received a bivalent booster (ancestral/BA.1). Convalescent sera from hamsters that had been experimentally infected with one of seven virus variants (ancestral, BA.1, BA.4, BA.5.2.1, XBB.1.5, XBB.1.16, XBB.2.3) were also tested here. The most contemporary variant, BA.2.86, was effectively neutralised by sera from hamsters infected with XBB.1.5 and XBB.1.16 but it was not neutralised by sera from those infected with BA.5.2.1. These data support the recommendations given by the WHO that a new vaccine was required and should consist of an XBB sub-lineage antigen.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.21.563398v1" target="_blank">Evaluation of the neutralising antibody response in human and hamster sera against SARS-CoV-2 variants up to and including BA.2.86 using an authentic virus neutralisation assay</a>
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<li><strong>Viral envelope proteins fused to multiple distinct fluorescent reporters to probe receptor binding</strong> -
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Enveloped viruses carry one or multiple proteins with receptor binding functionalities. Functional receptors can either be glycans, proteinaceous or both, recombinant protein approaches are instrumental to gain more insight into these binding properties. Visualizing and measuring receptor binding normally entails antibody detection or direct labelling, whereas direct fluorescent fusions are attractive tools in molecular biology. Here we report a suite of different fluorescent fusions, both N- and/or C- terminal, for influenza A virus hemagglutinins and SARS-CoV-2 spike RBD. The proteins contained a total of three or six fluorescent protein barrels and were applied directly to cells to determine receptor binding properties.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.23.563555v1" target="_blank">Viral envelope proteins fused to multiple distinct fluorescent reporters to probe receptor binding</a>
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<li><strong>Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant</strong> -
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In middle-late 2023, a sublineage of SARS-CoV-2 Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. Here, we performed multiscale investigations to reveal virological features of newly emerging EG.5.1 variant. Our phylogenetic-epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T, are critical to the increased viral fitness. Experimental investigations addressing the growth kinetics, sensitivity to clinically available antivirals, fusogenicity and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 is comparable to that of XBB.1.5. However, the cryo-electron microscopy reveals the structural difference between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible at least in our experimental setup. Our multiscale investigations provide the knowledge for understanding of the evolution trait of newly emerging pathogenic viruses in the human population.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.19.563209v1" target="_blank">Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant</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>Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers</strong> - <b>Conditions</b>: Viral Infection COVID-19 <br/><b>Interventions</b>: Drug: Aterixen <br/><b>Sponsors</b>: Valenta Pharm JSC <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>Long COVID Brain Fog: Cognitive Rehabilitation Trial</strong> - <b>Conditions</b>: Long COVID; Brain Fog; Cognitive Impairment; Cognitive Dysfunction; Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Speed of Processing Training; Behavioral: In-lab Instrumental Activities of Daily Living Training; Behavioral: In-lab Brain Health Training; Behavioral: Transfer Package; Behavioral: Follow Up Phone Calls; Behavioral: Vocational Rehabilitation; Behavioral: Peer Mentoring <br/><b>Sponsors</b>: University of Alabama at Birmingham; National Institute on Disability, Independent Living, and Rehabilitation Research <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>Paradoxical Response to Chest Wall Loading in Mechanically Ventilated Patients</strong> - <b>Conditions</b>: ARDS; COVID-19; Mechanical Ventilation Pressure High; Ventilator-Induced Lung Injury <br/><b>Interventions</b>: Diagnostic Test: Manual loading of the chest wall <br/><b>Sponsors</b>: HealthPartners Institute <br/><b>Withdrawn</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 Practical RCT of TCM in the Treatment of LCOVID and Analysis of Syndrome Types and Medication Characteristics.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Drug: Traditional Chinese medicine treatment; Drug: Western medicine treatment <br/><b>Sponsors</b>: Chinese University of Hong Kong <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>Narrative Intervention for Long COVID-19 (NICO)</strong> - <b>Conditions</b>: Long COVID; Long Covid19 <br/><b>Interventions</b>: Behavioral: Narrative Intervention for Long COVID-19 (NICO) <br/><b>Sponsors</b>: University of Colorado, Denver <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>Inspiratory Muscle Training in People With Long COVID-19- A Pilot Investigation.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: PrO2 <br/><b>Sponsors</b>: University of Bath; Swansea 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>Immunogenicity of Concomitant Administration of COVID-19 Vaccines With Influenza Vaccines</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccine Reaction; Contaminant Injected <br/><b>Interventions</b>: Biological: Omicron-containing COVID-19 vaccine; Biological: influenza vaccine <br/><b>Sponsors</b>: Catholic Kwandong University; Korea University Guro 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>Inspiratory Muscle Strength Training in Post-Covid Syndrome</strong> - <b>Conditions</b>: Cardiovascular Abnormalities; Post-COVID-19 Syndrome; Physical Exercise <br/><b>Interventions</b>: Other: Inspiratory muscle strength training <br/><b>Sponsors</b>: D’Or Institute for Research and Education <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>Home-Based Respiratory Muscle Strength Training Program for Individuals With Post-COVID-19 Persistent Dyspnea</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Dyspnea <br/><b>Interventions</b>: Device: Respiratory Muscle Strength Trainers <br/><b>Sponsors</b>: University of South Florida <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>Rural Tailored Communication to Promote SARS-CoV-2 Antibody Testing in Saliva</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Behavioral: General SARS-CoV-2 Communication; Behavioral: Rural-Targeted SARS-CoV-2 Communication <br/><b>Sponsors</b>: Michigan State University; National Cancer Institute (NCI); Johns Hopkins University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation Therapy for COVID-19</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Compensatory Cognitive Training for COVID-19; Behavioral: Holistic Cognitive Education <br/><b>Sponsors</b>: VA Office of Research and Development <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 Rehabilitation</strong> - <b>Conditions</b>: Rehabilitation; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders <br/><b>Interventions</b>: Behavioral: One day course; Behavioral: Individual follow-ups <br/><b>Sponsors</b>: University Hospital of North Norway; University of Bergen; Oslo University Hospital; Norwegian University of Science and Technology <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>Phase 3 Open-Label Controlled Trial of Convalescent Plasma in Early COVID-19 Infection</strong> - <b>Conditions</b>: Covid19 <br/><b>Interventions</b>: Drug: Convalescent Plasma; Other: Standard of Care <br/><b>Sponsors</b>: Larkin Community Hospital <br/><b>Withdrawn</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>Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection <br/><b>Interventions</b>: Drug: GST-HG171/ritonavir; Drug: ritonavir <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <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>Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments</strong> - <b>Conditions</b>: Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome; COVID-19; Fatigue; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Device: Monoplace Hyperbaric Chamber (Class III medical device). <br/><b>Sponsors</b>: Sunnybrook Health Sciences Centre <br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 neurotropism-induced anxiety and depression-like behaviors require Microglia activation</strong> - The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with a wide range of “long COVID” neurological symptoms. However, the mechanisms governing SARS-CoV-2 neurotropism and its effects on long-term behavioral changes remain poorly understood. Using a highly virulent mouse-adapted SARS-CoV-2 strain, denoted as SARS2-N501Y (MA30) , we demonstrated that intranasal inoculation of SARS2-N501Y (MA30) results in…</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>Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing</strong> - BACKGROUND: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false-negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive…</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>Intestinal injury and vasculitis biomarkers in cats with feline enteric coronavirus and effusive feline infectious peritonitis</strong> - OBJECTIVE: To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ORF3c is expressed in SARS-CoV-2-infected cells and inhibits innate sensing by targeting MAVS</strong> - Most SARS-CoV-2 proteins are translated from subgenomic RNAs (sgRNAs). While the majority of these sgRNAs are monocistronic, some viral mRNAs encode more than one protein. One example is the ORF3a sgRNA that also encodes ORF3c, an enigmatic 41-amino-acid peptide. Here, we show that ORF3c is expressed in SARS-CoV-2-infected cells and suppresses RIG-I- and MDA5-mediated IFN-β induction. ORF3c interacts with the signaling adaptor MAVS, induces its C-terminal cleavage, and inhibits the interaction…</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>Chemical Characteristics and Biological Activity Screening of Pistacia lentiscus Mastic Gum and Leaves from Turkiye</strong> - CONCLUSION: The mastic gum and leaves obtained from P. lentiscus may have great potential in terms of their chemical content, antiviral and cytotoxic activities. In ovo antiviral activity studies on the P. lentiscus were evaluated for the first time. Attributable to these properties, it is a sustainable, renewable natural resource that can be used as an additive and flavor in the food and pharmaceutical industries. 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>Evaluation of Potential Peptide-Based Inhibitors against SARS-CoV-2 and Variants of Concern</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has greatly affected all aspect of life. Although several vaccines and pharmaceuticals have been developed against SARS-CoV-2, the emergence of mutated variants has raised several concerns. The angiotensin-converting enzyme (ACE2) receptor cell entry mechanism of this virus has not changed despite the vast mutation in emerging variants. Inhibiting the spike protein by which the virus identifies the host ACE2 receptor is a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Some novel bioactivities of <em>Virgibacillus halodenitrificans</em> carotenoids, isolated from Wadi El-Natrun lakes</strong> - Carotenoids come in second among the most frequent natural pigments and are utilized in medications, nutraceuticals, cosmetics, food pigments, and feed supplements. Based on recent complementary work, Virgibacillus was announced for the first time as a member of Wadi El-Natrun salt and soda lakes microbiota, identified as Virgibacillus halodenitrificans, and named V. halodenitrificans DASH; hence, this work aimed to investigate several in vitro medicinal bioactivities of V. halodenitrificans…</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 and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome</strong> - INTRODUCTION: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main…</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 Naïve Phage Display Library-Derived Nanobody Neutralizes SARS-CoV-2 and Three Variants of Concern</strong> - CONCLUSION: Our study highlights a novel nanobody, Nb-H6, that may be useful therapeutically in SARS-CoV-2 and VOC outbreaks and pandemics. These findings also provide a molecular foundation for further studies into how nanobodies neutralize SARS-CoV-2 and variants and imply potential therapeutic targets for the treatment of COVID-19.</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>Macromolecules: Synthesis, antimicrobial, POM analysis and computational approaches of some glucoside derivatives bearing acyl moieties</strong> - Macromolecules i.e., carbohydrate derivatives are crucial to biochemical and medical research. Herein, we designed and synthesized eight methyl α-D-glucopyranoside (MGP) derivatives (2-8) in good yields following the regioselective direct acylation method. The structural configurations of the synthesized MGP derivatives were analyzed and verified using multiple physicochemical and spectroscopic techniques. Antimicrobial experiments revealed that almost all derivatives demonstrated noticeable…</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>Synthesis, structural characterization, antioxidant, cytotoxic activities and docking studies of schiff base Cu(II) complexes</strong> - By combining hydrazide with 2-Acetylpyridine, a hydrazone ligand (HL) was successfully created. Several copper (II) salts have been used to create three copper (II) hydrazone complexes (acetate, sulphate, and chloride). The hydrazide ligand and its copper (II) complexes (1-3) were studied via variety of analytical techniques, including elemental analysis, electronic, infrared, UV-vis Spectrum, XRD study, thermal analysis, also molar conductivity amounts. The spectrum results indicate that in all…</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>Pyrazolidinone-Based Peptidomimetic SARS-CoV-2 M<sup>pro</sup> inhibitors</strong> - The main protease (M^(pro)) of SARS-CoV-2 is an attractive drug target for COVID-19 treatment as it plays an integral role in the proliferation of coronavirus. Herein, we describe the investigation of β- and γ-lactams as electrophilic “warheads” for covalent binding to Cys145 of the M^(pro) active site. The highest inhibitory activity (IC(50) = 45 ± 3 μM) was achieved using a pyrazolidinone warhead attached to the targeting dipeptide. Importantly, the synergy of the warhead and the targeting…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro testing of host-targeting small molecule antiviral matriptase/TMPRSS2 inhibitors in 2D and 3D cell-based assays</strong> - The outbreak of coronavirus disease 2019 (COVID-19) pandemic strongly stimulated the development of small molecule antivirals selectively targeting type II transmembrane serine proteases (TTSP), required for the host-cell entry of numerous viruses. A set of 3-amidinophenylalanine derivatives (MI-21, MI-472, MI-477, MI-485, MI-1903 and MI-1904), which inhibit the cleavage of certain viral glycoproteins was characterized in 2D and 3D primary human hepatocyte models on collagen- and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Humoral immune response to SARS-CoV-2 and endemic coronaviruses in urban and indigenous children in Colombia</strong> - CONCLUSIONS: Overall, antibody titers, but in particular ACE2 binding inhibition are low within Colombian samples, requiring further investigation to determine any potential clinical significance.</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>ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2</strong> - Apoptosis signal-regulating kinase 1 (ASK1)/MAP3K5 is a stress response kinase that is activated by various stimuli. It is known as an upstream activator of p38- Mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) that are reactive oxygen species (ROS)-induced kinases. Accumulating evidence show that ROS accumulate in virus-infected cells. Here, we investigated the relationship between viruses and ASK1/p38MAPK or ASK1/JNK pathways. Our findings suggest that virus…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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