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169 lines
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<title>02 March, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic</strong> -
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<div>
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Background: Antibodies play a key role in the immune defence against infectious pathogens. Understanding the underlying process of B cell recognition is not only of fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas the nature of conformational B cell epitope recognition is inherently complicated, linear B cell epitopes offer a straightforward approach that potentially can be reduced to one of peptide recognition. Methods: Using an overlapping peptide approach representing the entire proteomes of the seven main coronaviruses known to infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents and eight pre-pandemic controls. Using a high-density peptide microarray platform, 13-mer peptides overlapping by 11 amino acids were in situ synthesised and incubated with the pooled primary serum samples, followed by development with secondary fluorochrome-labelled anti-IgG and -IgA antibodies. Interactions were detected by fluorescence detection. Strong Ig interactions encompassing consecutive peptides were considered to represent "high-fidelity regions" (HFRs). These were mapped to the coronavirus proteomes using a 60% homology threshold for clustering. Results: We identified 333 human coronavirus derived HFRs. Among these, 98 (29%) mapped to SARS-CoV-2, 144 (44%) mapped to one or more of the four circulating common cold coronaviruses (CCC), and 54 (16%) cross-mapped to both SARS-CoV-2 and CCCs. The remaining 37 (11%) mapped to either SARS-CoV or MERS-CoV. Notably, the COVID-19 serum was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas the pre-pandemic was skewed towards recognising CCC-mapped HFRs. In terms of absolute numbers of linear B cell epitopes, the primary targets are the ORF1ab protein (60%), the spike protein (21%), and the nucleoprotein (15%) in that order; however, in terms of epitope density, the order would be reversed. Conclusion: We identified linear B cell epitopes across coronaviruses, highlighting pan-, alpha-, beta-, or SARS-CoV-2-corona-specific B cell recognition patterns. These findings could be pivotal in deciphering past and current exposures to epidemic and endemic coronavirus. Moreover, our results suggest that pre-pandemic anti-CCC antibodies may cross-react against SARS-CoV-2, which could explain the highly variable outcome of COVID-19. Finally, the methodology used here offers a rapid and comprehensive approach to high-resolution linear B-cell epitope mapping, which could be vital for future studies of emerging infectious diseases.
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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.biorxiv.org/content/10.1101/2024.02.29.582263v1" target="_blank">Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques</strong> -
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<div>
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Antibodies represent a primary mediator of protection against respiratory viruses such as SARS-CoV-2. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are not well understood. Here we show that antibody correlates of protection against SARS-CoV-2 challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, neutralizing antibodies were the strongest correlate of protection and were linked to Spike-specific binding antibodies and other extra-neutralizing antibody functions that create a larger protective network. In contrast, in bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal Spike-specific IgG, IgA/secretory IgA, and Fc{gamma}-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites. The correlation of ADCP and other Fc functional antibody responses with protection in BAL suggests that these antibody responses may be critical for protection against SARS-CoV-2 Omicron challenge in mucosa.
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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.biorxiv.org/content/10.1101/2024.03.01.582951v1" target="_blank">Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques</a>
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</div></li>
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<li><strong>The landscape of biomedical research</strong> -
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<div>
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The number of publications in biomedicine and life sciences has rapidly grown over the last decades, with over 1.5 million papers now being published every year. This makes it difficult to keep track of new scientific works and to have an overview of the evolution of the field as a whole. Here we present a 2D map of the entire corpus of biomedical literature, and argue that it provides a unique and useful overview of the life sciences research. We based our atlas on the abstract texts of 21 million English articles from the PubMed database. To embed the abstracts into 2D, we used the large language model PubMedBERT, combined with t-SNE tailored to handle samples of our size. We used our atlas to study the emergence of the Covid-19 literature, the evolution of the neuroscience discipline, the uptake of machine learning, the distribution of gender imbalance in academic authorship, and the distribution of retracted paper mill articles. Furthermore, we present an interactive web version of our atlas that allows easy exploration and will enable further insights and facilitate future research.
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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.biorxiv.org/content/10.1101/2023.04.10.536208v4" target="_blank">The landscape of biomedical research</a>
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</div></li>
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<li><strong>Sibling Relationships and Parental Interventions to Sibling Bullying During Covid-19: A Qualitative Comparison of British and Turkish Families of Autistic Adolescents</strong> -
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<div>
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Background and aims: Despite its high potential for affecting sibling relationships, few studies have explored the impact of the Covid-19 pandemic on this important family dynamic. Of these, the reported evidence has been inconsistent across cultures and lacks cross-cultural comparability. For the first time, we investigated cross-cultural variability in the impact of Covid-19, and the restrictions associated with it, on sibling relationships of autistic adolescents from a Western (United Kingdom) and non-Western (Turkey) country. We also explored how British and Turkish parents intervene in negative sibling interactions – i.e., sibling bullying –when witnessed. Methods: Parents of 164 British and 96 Turkish autistic adolescents, aged 9-20 years, were asked how they perceived the effects of Covid-19 on their children’s sibling relationships, and how they were most likely to react to instances of sibling bullying. Free response data from parents were analysed using qualitative content analysis. Results: Our findings indicated more cross-cultural similarities than differences between British and Turkish families. The majority of both British and Turkish parents indicated that Covid-19 worsened sibling relationships between their autistic and non-autistic children. An overwhelming majority of British and Turkish parents also said that they would step in directly when witnessing sibling bullying. Despite the high volume of cross-cultural similarities generally, we also found some cross-cultural differences, for instance in relation to the most common negative impact of Covid-19 on sibling relationships and the most preferred parental responses to sibling bullying. Conclusions and implication: Implications and suggestions are discussed in more detail, drawing on the Etic approach to cross-cultural psychology.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/nqez3/" target="_blank">Sibling Relationships and Parental Interventions to Sibling Bullying During Covid-19: A Qualitative Comparison of British and Turkish Families of Autistic Adolescents</a>
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</div></li>
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<li><strong>Sputum production and salivary microbiome in COVID-19 patients reveals oral-lung axis</strong> -
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<div>
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Objective: SARS-CoV-2 is a severe respiratory disease that primarily targets the lungs and was the leading cause of death worldwide during the pandemic. Investigating the intricate interplay between the oral microbiome and inflammatory cytokines during the acute phase of infection is crucial for understanding host immune responses. This study aimed to explore the relationship between the oral microbiome and cytokines in COVID-19 patients, specifically examining those with and without sputum production. Methods: Saliva and blood samples from 50 COVID-19 patients were subjected to 16S ribosomal RNA gene sequencing to analyze the oral microbiome. Additionally, 65 saliva and serum cytokines were assessed using Luminex multiplex analysis. The Mann-Whitney test compared cytokine levels between individuals with and without sputum production. Results: Our study revealed significant differences in the membership (Jaccard dissimilarity: p=0.016) and abundance (PhILR dissimilarity: p=0.048; metagenomeSeq) of salivary microbial communities between COVID-19 patients with and without sputum production. Seven bacterial genera, including Prevotella, Streptococcus, Actinomyces, Atopobium, Filifactor, Leptotrichia, and Selenomonas, were present in statistically higher proportions of patients with sputum production (p<0.05, Fisher's exact test). Eight bacterial genera, including Prevotella, Megasphaera, Stomatobaculum, Leptotrichia, Veillonella, Actinomyces, Atopobium, and Corynebacteria were significantly more abundant in the sputum-producing group, while Lachnoacaerobaculum was notably more prevalent in the non-sputum-producing group (p<0.05, ANCOM-BC).We observed a significant positive correlation between salivary IFN-gamma (Interferon-gamma) and Eotaxin2/CCL24 (chemokine ligand 24) with sputum production. Conversely, negative correlations were noted in serum MCP3/CCL7 (monocyte-chemotactic protein 3/Chemokine ligand 7), MIG/CXCL9 (Monokine induced by gamma/Chemokine ligand 9), IL1 beta (interleukin 1 beta), and SCF (stem cell factor) with sputum production (p<0.05, Mann-Whitney test). Conclusion: Substantial distinctions in salivary microbial communities were evident between COVID-19 patients with and without sputum production, emphasizing the notable impact of sputum production on the oral microbiome and cytokine levels during the acute phase of infection.
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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.biorxiv.org/content/10.1101/2024.02.29.582705v1" target="_blank">Sputum production and salivary microbiome in COVID-19 patients reveals oral-lung axis</a>
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</div></li>
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<li><strong>Discovery of anti-SARS-CoV-2 S2 protein antibody CV804 with broad-spectrum reactivity with various beta coronaviruses and analysis of its pharmacological properties in vitro and in vivo</strong> -
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<div>
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SARS-CoV-2 pandemic alerts us that spillovers of various animal coronaviruses to human in the future may bring us enormous damages. Thus, there is a significant need of antibody-based drugs to treat patients infected with previously unseen coronaviruses. CV804 against the S2 domain of the spike protein, which is less prone to mutations. CV804 shows not only broad cross-reactivities with representative 20 animal-origin coronaviruses but also with diseases-associated human beta coronaviruses including SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-HKU1 and mutant strains of SARS-CoV-2. Other than that, the main characteristics of CV804 are that it has strong antibody-dependent cellular cytotoxicity (ADCC) activity to SARS-CoV2 spike protein-expressed cells in vitro and completely lacks virus-neutralization activity. Comprehensively in animal models, CV804 suppressed disease progression by SARS-CoV-2 infection. Structural studies using HDX-MS and point mutations of recombinant spike proteins revealed that CV804 binds to a unique epitope within the highly conserved S2 domain of the spike proteins of various coronaviruses. Based on the overall data, we suggest that the non-neutralizing CV804 antibody recognizes the conformational structure of the spike protein expressed on the surface of the infected cells and weakens the viral virulence by supporting host immune cells attack through ADCC activity in vivo. CV804 epitope identified in this study is not only useful for the design of pan-corona antibody therapeutics but also to design next-generation coronavirus vaccines and antiviral drugs.
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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.biorxiv.org/content/10.1101/2024.02.28.582480v1" target="_blank">Discovery of anti-SARS-CoV-2 S2 protein antibody CV804 with broad-spectrum reactivity with various beta coronaviruses and analysis of its pharmacological properties in vitro and in vivo</a>
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</div></li>
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<li><strong>Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination</strong> -
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<div>
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Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activity in vitro but several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.
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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.biorxiv.org/content/10.1101/2024.02.28.582613v1" target="_blank">Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination</a>
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</div></li>
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<li><strong>Peptide Mold: A Novel Strategy for Mapping Potential Binding Sites in Protein Targets</strong> -
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<div>
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A novel concept titled Peptide Mold for mapping potential binding sites in protein targets is presented. A large multiconformer tetrapeptide library comprising of 32 million conformations of all possible combinations of naturally-occurring amino acids was constructed and used for molecular docking analysis in the substrate-binding site of SARS-CoV-2 PLpro enzyme. The top-ranking, structurally-diverse tetrapeptide docked conformations (symbolizing peptide mold, analogous to a clay mold) were used then for elucidating a five-point pharmacophore. Ligand-based virtual screening of a large, multiconformer library of phytoconstituents using the derived five-point pharmacophore led to identification of potential binders for SARS-CoV-2 PLpro at its substrate-binding site. The approach is based on generating the imprint of a macromolecular binding site (cavity) using tetrapeptides (clay), thereby generating a reverse mold (with definitive shape and size), which can further be used for identifying small-molecule ligands matching the captured features of the target binding site. The approach is based on the fact that the individual amino acids in the tetrapeptide represent all possible drug-receptor interaction features (electrostatic, H-bonding, van der Waals, dispersion and hydrophobic among others). The peptide mold approach can be extended to any protein target for mapping the binding site(s), and further use of the generated pharmacophore model for virtual screening of potential binders. The peptide mold approach is a robust, hybrid computational screening strategy, overcoming the present limitations of structure-based methods, e.g., molecular docking and the ligand-based methods such as pharmacophore search. Exploration of the peptide mold strategy is expected to yield high-quality, reliable and interesting virtual hits in the computational screening campaigns during the hit and lead identification stages.
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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.biorxiv.org/content/10.1101/2024.02.28.582665v1" target="_blank">Peptide Mold: A Novel Strategy for Mapping Potential Binding Sites in Protein Targets</a>
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</div></li>
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<li><strong>Influencers in Tourism Digital Marketing: A Comprehensive Literature Review</strong> -
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<div>
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Almost all business sectors in various developed and developing countries have realized the importance of transforming conventional marketing to digital marketing, the goal is to increase sales. Many marketing strategies can be applied to increase sales, including utilizing influencers in digital marketing. This study aims to identify digital marketing strategies that have been widely used by researchers in various countries and look for new models or new strategies that are relevant to be applied in developing countries after COVID-19 through a systematic literature review. The author searched for scientific articles on the Scopus database that were in English and fully accessible. This research reviewed 19 articles using a systematic literature review. The results showed that the majority of related research was published in 2018-2022, ten related articles were published in 2022 with three articles published in Spain. All authors proposed various variables, but generally conventional in digital marketing, while not many authors concentrated on the utilization of influencers in carrying out digital marketing. Therefore, this research offers a digital marketing strategy combined with the role of influencers in tourist destinations that have a competitive advantage.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/m97kd/" target="_blank">Influencers in Tourism Digital Marketing: A Comprehensive Literature Review</a>
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</div></li>
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<li><strong>Curcumin and turmeric extract inhibit SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion</strong> -
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<div>
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Turmeric extract (TE) with curcumin as its main active ingredient has been studied as a potential COVID-19 therapeutic. Curcumin has been studied in silico and in vitro against a naive SARS-CoV-2 virus, yet little is known about TE’s impact on SARS-CoV-2 infection. Moreover, no study reveals the potential of both curcumin and TE on the inhibition of SARS-CoV-2 cell-to-cell transmission. Here, we investigated the effects of both curcumin and TE on inhibiting SARS-CoV-2 entry and cell-to-cell transmission using pseudovirus (PSV) and syncytia models. We performed a PSV entry assay in 293T or 293 cells expressing hACE2. The cells were pretreated with curcumin or TE and then treated with PSV with or without the test samples. Next, we carried out syncytia assay by co-transfecting 293T cells with plasmids encoding spike, hACE2, and TMPRSS2 to be treated with the test samples. The results showed that in PSV entry assay on 293T/hACE/TMPRSS2 cells, both curcumin and TE inhibited PSV entry at concentrations of 1 M and 10 M for curcumin and 1 g/ml and 10 g/ml for TE. Moreover, both curcumin and TE reduced syncytia formation compared to control cells. Our study shows that TE and curcumin are potential inhibitors of SARS-CoV-2 infection at entry points, either by direct or indirect infection models.
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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.biorxiv.org/content/10.1101/2023.09.28.560070v2" target="_blank">Curcumin and turmeric extract inhibit SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion</a>
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</div></li>
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<li><strong>The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in infected and immune suppressed mice</strong> -
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<div>
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Objectives: Immunocompromised individuals are susceptible to severe COVID-19 and potentially contribute to the emergence of variants with altered pathogenicity due to persistent infection. This study investigated the impact of immunosuppression on SARS-CoV-2 infection in k18-hACE2 mice and the effectiveness of antiviral treatments in this context. Methods: Mice were immunosuppressed using cyclophosphamide and infected with a B lineage of SARS-CoV-2. Molnupiravir and nirmatrelvir, alone and in combination, were administered and viral load and viral sequence diversity was assessed. Results: Treatment of infected but immune compromised mice with both compounds either singly or in combination resulted in decreased viral loads and pathological changes compared to untreated animals. Treatment also abrogated infection of neuronal tissue. However, no consistent changes in the viral consensus sequence were observed, except for the emergence of the S:H655Y mutation. Molnupiravir, but not nirmatrelvir or immunosuppression alone, increased the transition/transversion (Ts/Tv) ratio, indicative of A>G and C>U mutations. Notably, immunosuppression itself did not appear to promote the emergence of mutations characteristic of variants of concern (VOCs). Conclusions: Further investigations are warranted to fully understand the role of immunocompromised individuals in VOC development and to inform optimised public health strategies. It is more likely that immunodeficiency promotes viral persistence but does not necessarily lead to substantial consensus-level changes in the absence of antiviral selection pressure. Molnupiravir, compared to nirmatrelvir, shows a stronger mutagenic effect in this model.
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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.biorxiv.org/content/10.1101/2024.02.27.582110v1" target="_blank">The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in infected and immune suppressed mice</a>
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</div></li>
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<li><strong>Virological traits of the SARS-CoV-2 BA.2.87.1 lineage</strong> -
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<div>
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The highly mutated SARS-CoV-2 BA.2.87.1 lineage was recently detected in South Africa, but its transmissibility is unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for high transmissibility.
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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.biorxiv.org/content/10.1101/2024.02.27.582254v1" target="_blank">Virological traits of the SARS-CoV-2 BA.2.87.1 lineage</a>
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</div></li>
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<li><strong>Attenuated replication and damaging effects of SARS-CoV-2 Omicron in an intestinal epithelial barrier model</strong> -
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<div>
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Many COVID-19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function may play a key role in Long COVID. Despite its importance, the impact of SARS-CoV-2 on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco-2 cells, mucus-secreting HT29 cells and human Raji cells. This gut epithelial model allows efficient differentiation of Caco-2 cells into microfold-like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS-CoV-2 infection. Early strains of SARS-CoV-2 and the Delta variant replicated with high efficiency, severely disrupted barrier function, and depleted tight junction proteins, such as claudin-1, occludin and ZO-1. In comparison, Omicron subvariants also depleted ZO-1 from tight junctions but had fewer damaging effects on mucosal integrity and barrier function. Remdesivir and the TMPRSS2 inhibitor Camostat prevented SARS-CoV-2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS-CoV-2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains.
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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/10.1101/2024.02.28.582510v1" target="_blank">Attenuated replication and damaging effects of SARS-CoV-2 Omicron in an intestinal epithelial barrier model</a>
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</div></li>
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<li><strong>Designed mosaic nanoparticles enhance cross-reactive immune responses in mice</strong> -
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<div>
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Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2COMs; mosaic-5COM), and (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naive and COVID-19 pre-vaccinated mice revealed that mosaic-7COM elicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7COM targeted conserved RBD epitopes. Mosaic-2COMs and mosaic-5COM elicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7COM to protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.28.582544v1" target="_blank">Designed mosaic nanoparticles enhance cross-reactive immune responses in mice</a>
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<li><strong>The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2</strong> -
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The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity for viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in the receptor binding domain of the S1 subunit of the spike glycoprotein have led to considerable escape from antibody responses, reducing the efficacy of vaccines and monoclonal antibody (mAb) therapies. Therefore, there is a need to interrogate more constrained regions of Spike, such as the S2 subdomain. Here, we describe a collection of S2 mAbs from two SARS-CoV-2 convalescent individuals that target multiple regions in the S2 subdomain and can be grouped into at least five epitope classes. Most did not neutralize SARS-CoV-2 with the exception of C20.119, which bound to a highly conserved epitope in the fusion peptide and showed broad binding and neutralization activity across SARS-CoV-2, SARS-CoV-1, and closely related zoonotic sarbecoviruses. Several of the S2 mAbs tested mediated antibody-dependent cellular cytotoxicity (ADCC) at levels similar to the S1 mAb S309 that was previously authorized for treatment of SARS-CoV-2 infections. Three of the mAbs with ADCC function also bound to spike trimers from HCoVs, such as MERS-CoV and HCoV-HKU1. Our findings suggest there are diverse epitopes in S2, including functional S2 mAbs with HCoV and sarbecovirus breadth that likely target functionally constrained regions of spike. These mAbs could be developed for potential future pandemics, while also providing insight into ideal epitopes for eliciting a broad HCoV response.
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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/10.1101/2024.02.26.582219v1" target="_blank">The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2</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>Phase II Clinical Study of SHEN211 Tablets in the Treatment of Mild and Moderate Novel Corona Virus Infection (COVID-19)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets <br/><b>Sponsors</b>: JKT Biopharma 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>INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>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 Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo <br/><b>Sponsors</b>: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited <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 to Evaluate the Safety & Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: IMNN-101 <br/><b>Sponsors</b>: Imunon <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>Effectiveness of a Nasal Spray on Viral Respiratory Infections</strong> - <b>Conditions</b>: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold <br/><b>Interventions</b>: Device: Nasal Spray HSV Treatment <br/><b>Sponsors</b>: CEN Biotech; Urgo Research, Innovation & Development <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>GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: GS-441524; Drug: Placebo <br/><b>Sponsors</b>: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 <br/><b>Interventions</b>: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) <br/><b>Sponsors</b>: Selda Sarıkaya; Zonguldak Bulent Ecevit University <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mindfulness-based Mobile Applications Program</strong> - <b>Conditions</b>: COVID-19; Cell Phone Use; Nurse; Mental Health <br/><b>Interventions</b>: Device: mindfulness-based mobile applications program <br/><b>Sponsors</b>: Yu-Chien Huang <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt</strong> - <b>Conditions</b>: Mucormycosis; Rhinocerebral (Etiology); COVID-19 <br/><b>Interventions</b>: Procedure: debridment <br/><b>Sponsors</b>: Nasser Institute For Research and Treatment <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 <br/><b>Interventions</b>: Drug: Hyperbaric oxygen <br/><b>Sponsors</b>: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Attention Training for COVID-19 Related Distress</strong> - <b>Conditions</b>: Anxiety <br/><b>Interventions</b>: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training <br/><b>Sponsors</b>: Palo Alto University <br/><b>Not yet recruiting</b></p></li>
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</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>Priming congruence and COVID-19 vaccination intention: a mediation analysis</strong> - CONCLUSIONS: Implications of these results are discussed in light of the socially situated cognition perspective and the congruence of (a) a societal context of communication toward the vaccine and the unvaccinated, (b) the participant’s degree of adherence to that communication, (c) the theme of priming, whether or not related to feeling connected to others. Implications of materialism priming are discussed, and the effect of commitment on intention to get vaccinated.</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 subunit-based influenza/SARS-CoV-2 Omicron combined vaccine induced potent protective immunity in BALB/c mice</strong> - Infection with influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant risk to human life, health, and the global economy. Vaccination is one of the most effective strategies in the fight against infectious viruses. In this study, we, for the first time, have evaluated the immunogenicity and protective effect of an influenza/SARS-CoV-2 Omicron subunit combined vaccine adjuvanted with MF59 and administered to BALB/c mice. Results showed that…</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>Nudging Public Health Behaviors to Prevent COVID-19: A Systematic Review</strong> - Many countries have implemented strict preventive measures and mandatory policies to curb virus transmission during the COVID-19 pandemic. Some have adopted softer approaches, such as nudge-based intervention, to influence public health behavior. This systematic review, conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines, aims to determine if the nudge-based intervention can effectively influence people’s preventive behavior during 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>IFN-gamma decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3beta signaling pathway</strong> - Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8^(+) T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8^(+) T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3β may regulate the INF-γ/PD-1 axis in CD8^(+) T cells from 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>Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters</strong> - CONCLUSION: Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases 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>Synthesis, SARS-CoV-2 main protease inhibition, molecular docking and in silico ADME studies of furanochromene-quinoline hydrazone derivatives</strong> - Seven furanochromene-quinoline derivatives containing a hydrazone linker were synthesized by condensing a furanochromene hydrazide with 2-, 3-, 4-, 5-, 6-, and 8-quinoline carbaldehydes, including 8-hydroxyquinoline-2-carbaldehye. Structure-activity correlations were investigated to determine the influence of the location of the hydrazone linker on the quinoline unit on SARS-CoV-2 M^(pro) enzyme inhibition. The 3-, 5-, 6- and 8-substituted derivatives showed moderate inhibition of SARS-CoV-2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Oligoadenylate synthetase 1 displays dual antiviral mechanisms in driving translational shutdown and protecting interferon production</strong> - In response to viral infection, how cells balance translational shutdown to limit viral replication and the induction of antiviral components like interferons (IFNs) is not well understood. Moreover, how distinct isoforms of IFN-induced oligoadenylate synthetase 1 (OAS1) contribute to this antiviral response also requires further elucidation. Here, we show that human, but not mouse, OAS1 inhibits SARS-CoV-2 replication through its canonical enzyme activity via RNase L. In contrast, both mouse…</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 mechanisms of cell tropism in various organs considering host factors</strong> - A critical step in the drug design for SARS-CoV-2 is to discover its molecular targets. This study comprehensively reviewed the molecular mechanisms of SARS-CoV-2, exploring host cell tropism and interaction targets crucial for cell entry. The findings revealed that beyond ACE2 as the primary entry receptor, alternative receptors, co-receptors, and several proteases such as TMPRSS2, Furin, Cathepsin L, and ADAM play critical roles in virus entry and subsequent pathogenesis. Additionally,…</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>Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies</strong> - Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here, we uncover the role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via…</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>Microfluidics produced ATRA-loaded PLGA NPs reduced tuberculosis burden in alveolar epithelial cells and enabled high delivered dose under simulated human breathing pattern in 3D printed head models</strong> - Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is second only to COVID-19 as the top infectious disease killer worldwide. Multi-drug resistant TB (MDR-TB) may arise because of poor patient adherence to medications due to lengthy treatment duration and side effects. Delivering novel host directed therapies (HDT), like all trans retinoic acid (ATRA) may help to improve drug regimens and reduce the incidence of MDR-TB. Local delivery of ATRA to the site of infection leads to higher…</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>Miquelianin: primary antioxidant power and Mpro SARS-CoV-2 non-covalent inhibition capabilities from computational investigations</strong> - The antioxidant power of quercetin-3-O-glucuronide (miquelianin) has been studied, at the density functional level of theory, in both lipid-like and aqueous environments. In the aqueous phase, the computed pKa equilibria allows the identification of the neutral and charged species present in solution that can react with the •OOH radical. The Hydrogen Atom Transfer (HAT), Single Electron Transfer (SET) and Radical Adduct Formation (RAF) mechanisms were considered and the individual, total 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>Exploring Retrograde Trafficking: Mechanisms and Consequences in Cancer and Disease</strong> - Retrograde trafficking (RT) orchestrates the intracellular movement of cargo from the plasma membrane, endosomes, Golgi or endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) in an inward/ER-directed manner. RT works as the opposing movement to anterograde trafficking (outward secretion), and the two work together to maintain cellular homeostasis. This is achieved through maintaining cell polarity, retrieving proteins responsible for anterograde trafficking and redirecting proteins…</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>Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study</strong> - One of the major pathomechanisms of COVID-19 is the interplay of hyperinflammation and disruptions in coagulation processes, involving thrombocytes. Antiplatelet therapy (AP) by anti-inflammatory effect and inhibition of platelet aggregation may affect these pathways. The aim of this study was to investigate if AP has an impact on the in-hospital course and medium-term outcomes in hospitalized COVID-19 patients. The study population (2170 COVID-19 patients: mean ± SD age 60 ± 19 years old, 50%…</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>Pan-viral propagation blockade by inhibiting host cell PNPT1</strong> - Successful viral propagation within infected cells necessitates the viruses’ ability to overcome the cellular integrated stress response (ISR), triggered during viral infection, which in turn inhibits general protein translation. In our study, we unveil a shared tactic employed by viruses to suppress ISR by upregulating host cell polyribonucleotide nucleotidyltransferase 1 (PNPT1). The propagation of adenovirus, murine cytomegalovirus, and hepatovirus within their respective host cells induces…</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>Synergistic Binding of SARS-CoV-2 to ACE2 and Gangliosides in Native Lipid Membranes</strong> - Viruses utilize cell surface glycans and plasma membrane receptors to attain an adequate attachment strength for initiating cellular entry. We show that SARS-CoV-2 particles bind to endogenous ACE2 receptors and added sialylated gangliosides in near-native membranes. This was explored using supported membrane bilayers (SMBs) that were formed using plasma membrane vesicles having endogenous ACE2 and GD1a gangliosides reconstituted in lipid vesicles. The virus binding rate to the SMBs is…</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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