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180 lines
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<title>15 March, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Function and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages</strong> -
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<div>
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The SARS-CoV-2 variant, Omicron (B.1.1.529), rapidly swept the world since its emergence. Compared with previous variants, Omicron has a high number of mutations, especially those in its spike glycoprotein that drastically dampen or abolish the efficacy of currently available vaccines and therapeutic antibodies. Several major sublineages of Omicron evolved, including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, BA.4/5, and BA.2.75, which rapidly changing the global and regional landscape of the pandemic. Although vaccines are available, therapeutic antibodies remain critical for infected and especially hospitalized patients. To address this, we have designed and generated a panel of human/humanized therapeutic bispecific antibodies against Omicron and its sub-lineage variants, with activity spectrum against other lineages. Among these, the top clone CoV2-0213 has broadly potent activities against multiple SARS-CoV-2 ancestral and Omicron lineages, including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, BA.4/5, and BA.2.75. We have solved the cryo-EM structure of the lead bi-specific antibody CoV-0213 and its major Fab arm MB.02. Three-dimensional structural analysis shows distinct epitope of antibody - spike receptor binding domain (RBD) interactions and reveals that both Fab fragments of CoV2-0213 can simultaneously target one single spike RBD or two adjacent ones in the same spike trimer, further corroborating its mechanism of action. CoV2-0213 represents a unique and potent broad-spectrum SARS-CoV-2 neutralizing bispecific antibody (nbsAb) against the currently circulating major Omicron variants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.3, and BA.4/5). CoV2-0213 is primarily human and ready for translational testing as a countermeasure against the ever-evolving pathogen.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.09.503414v2" target="_blank">Function and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages</a>
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</div></li>
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<li><strong>Nanobodies against SARS-CoV-2 reduced virus load in the brain of challenged mice and neutralized Wuhan, Delta and Omicron Variants</strong> -
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<div>
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In this work, we developed llama-derived nanobodies (Nbs) directed to the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Nanobodies were selected after the biopanning of two Nb-libraries, one of which was generated after the immunization of a llama (lama glama) with the bovine coronavirus (BCoV) Mebus, and another with the full-length pre-fused locked S protein (S-2P) and the RBD from the SARS-CoV-2 Wuhan strain (WT). Most of the neutralizing Nbs selected with either RBD or S-2P from SARS-CoV-2 were directed to RBD and were able to block S2P/ACE2 interaction. Three Nbs recognized the N-terminal domain (NTD) of the S-2P protein as measured by competition with biliverdin, while some non-neutralizing Nbs recognize epitopes in the S2 domain. One Nb from the BCoV immune library was directed to RBD but was non-neutralizing. Intranasal administration of Nbs induced protection ranging from 40% to 80% against COVID-19 death in k18-hACE2 mice challenged with the WT strain. Interestingly, protection was not only associated with a significant reduction of virus replication in nasal turbinates and lungs, but also with a reduction of virus load in the brain. Employing pseudovirus neutralization assays, we were able to identify Nbs with neutralizing capacity against the Alpha, Beta, Delta and Omicron variants. Furthermore, cocktails of different Nbs performed better than individual Nbs to neutralize two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest these Nbs can potentially be used as a cocktail for intranasal treatment to prevent or treat COVID-19 encephalitis, or modified for prophylactic administration to fight this disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.14.532528v1" target="_blank">Nanobodies against SARS-CoV-2 reduced virus load in the brain of challenged mice and neutralized Wuhan, Delta and Omicron Variants</a>
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</div></li>
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<li><strong>Murine Alveolar Macrophages Rapidly Accumulate Intranasally Administered SARS-CoV-2 Spike Protein leading to Neutrophil Recruitment and Damage</strong> -
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<div>
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The trimeric SARS-CoV-2 Spike protein mediates viral attachment facilitating cell entry. Most COVID-19 vaccines direct mammalian cells to express the Spike protein or deliver it directly via inoculation to engender a protective immune response. The trafficking and cellular tropism of the Spike protein in vivo and its impact on immune cells remains incompletely elucidated. In this study we inoculated mice intranasally, intravenously, and subcutaneously with fluorescently labeled recombinant SARS-CoV-2 Spike protein. Using flow cytometry and imaging techniques we analyzed its localization, immune cell tropism, and acute functional impact. Intranasal administration led to rapid lung alveolar macrophage uptake, pulmonary vascular leakage, and neutrophil recruitment and damage. When injected near the inguinal lymph node medullary, but not subcapsular macrophages, captured the protein, while scrotal injection recruited and fragmented neutrophils. Wide-spread endothelial and liver Kupffer cell uptake followed intravenous administration. Human peripheral blood cells B cells, neutrophils, monocytes, and myeloid dendritic cells all efficiently bound Spike protein. Exposure to the Spike protein enhanced neutrophil NETosis and augmented human macrophage TNF- and IL-6 production. Human and murine immune cells employed C-type lectin receptors and Siglecs to help capture the Spike protein. This study highlights the potential toxicity of the SARS-CoV-2 Spike protein for mammalian cells and illustrates the central role for alveolar macrophage in pathogenic protein uptake.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.13.532446v1" target="_blank">Murine Alveolar Macrophages Rapidly Accumulate Intranasally Administered SARS-CoV-2 Spike Protein leading to Neutrophil Recruitment and Damage</a>
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</div></li>
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<li><strong>Deep physico-chemical characterization of individual serum antibody responses against SARS-CoV-2 RBD using a dual titration microspot assay</strong> -
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<div>
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Antigen specific humoral immunity can be characterized by the analysis of serum antibodies. While serological assays for the measurement of antibody levels and of neutralization potential against SARS-CoV-2 are available, these are not quantitative in the biochemical sense. Yet, understanding the biology of COVID-19 would need an unambiguous, complete, quantitative, comparable measurement of specific serum antibodies. Here we describe a fluorescent, dual-titration immunoassay, which provides the physico-chemical parameters that are both necessary and sufficient to quantitatively characterize the humoral immune response. We used recombinant Receptor Binding Domain of SARS-CoV-2 as antigen on microspot arrays and varied the concentration of both the antigen and serum antibodies from vaccinated persons to obtain a measurement matrix of binding data. Binding curves were fitted using a novel algorithm to obtain thermodynamic variables of binding. We defined the standard state for a system of serum antibodies and antigen and showed how a normalized generalized logistic function is related to thermodynamic activity, standard concentration and activity coefficient. The utility of the method is demonstrated by defining the composition of tested sera with respect to immunoglobulin classes, affinity, concentration, and thermodynamic activity. The proposed fluorescent dual-titration microspot immunoassay can generate truly quantitative serological data that is suitable for immunological, medical and systems biological analysis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.14.532012v1" target="_blank">Deep physico-chemical characterization of individual serum antibody responses against SARS-CoV-2 RBD using a dual titration microspot assay</a>
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</div></li>
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<li><strong>Persistence of SARS-CoV-2 and its surrogate, bacteriophage Phi6, on surfaces and in water</strong> -
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<div>
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The COVID-19 pandemic has motivated research on the persistence of infectious SARS-CoV-2 in environmental reservoirs such as surfaces and water. Viral persistence data has been collected for SARS-CoV-2 and its surrogates, including bacteriophage Phi6. Despite its wide use, no side-by-side comparisons between Phi6 and SARS-CoV-2 exist. Here, we quantified the persistence of SARS-CoV-2 and Phi6 on surfaces (plastic and metal) and in water and evaluated the influence that the deposition solution has on viral persistence by using four commonly used deposition solutions: two culture media (DMEM and Tryptone Soya Broth (TSB)), Phosphate Buffered Saline (PBS), and human saliva. Phi6 remained infectious in water significantly longer than SARS-CoV-2, having a half-life of 27 hours as compared with 15 hours for SARS-CoV-2. The persistence of viruses on surfaces was significantly influenced by the virus used and the deposition solution, but not by the surface material. Phi6 remained infectious significantly longer than SARS-CoV-2 when the inoculation solution was culture media (DMEM, TSB) and saliva. Using culture media and saliva led to half-lives between 9 hours and 2 weeks for Phi6, as compared to 0.5 to 2 hours for SARS-CoV-2. Using PBS as a deposition solution led to half-lives shorter than 4 hours for both viruses on all surfaces. Our results showed that, although it has been frequently used as a surrogate for coronaviruses, bacteriophage Phi6 is not an adequate surrogate for studies quantifying SARS-CoV-2 persistence, as it over-estimates infectiousness. Additionally, our findings reveal the need of using adequate deposition solutions when evaluating viral persistence on surfaces.
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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/10.1101/2023.03.14.532590v1" target="_blank">Persistence of SARS-CoV-2 and its surrogate, bacteriophage Phi6, on surfaces and in water</a>
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<li><strong>Discovering Social Determinants of Health from Case Reports using Natural Language Processing: Algorithmic Development and Validation</strong> -
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Background: Social determinants of health are non-medical factors that influence health outcomes (SDOH). There is a wealth of SDOH information available via electronic health records, clinical reports, and social media, usually in free text format, which poses a significant challenge and necessitates the use of natural language processing (NLP) techniques to extract key information. Objective: The objective of this research is to advance the automatic extraction of SDOH from clinical texts. Setting and Data: The case reports of COVID-19 patients from the published literature are curated to create a corpus. A portion of the data is annotated by experts to create gold labels, and active learning is used for corpus re-annotation. Methods: A named entity recognition (NER) framework is developed and tested to extract SDOH along with a few prominent clinical entities (diseases, treatments, diagnosis) from the free texts. Results: The proposed NER implementation achieves an accuracy (F1-score) of 92.98% on our test set and generalizes well on benchmark data. A careful analysis of case examples demonstrates the superiority of the proposed approach in correctly classifying the named entities. Conclusions: NLP can be used to extract key information, such as SDOH from free texts. A more accurate understanding of SDOH is needed to further improve healthcare outcomes.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.30.22282946v3" target="_blank">Discovering Social Determinants of Health from Case Reports using Natural Language Processing: Algorithmic Development and Validation</a>
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</div></li>
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<li><strong>How long is the long COVID? a retrospective analysis of football players in two major European Championships.</strong> -
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Objectives, the goal of this study was to investigate the correlation between SARS-CoV-2 infection and muscle injuries among a large sample of professional soccer players. Methods, A retrospective cohort study was conducted on professional soccer players from the Serie A and LaLiga leagues during the 2019-2020 and 2020-2021 football seasons. The players were divided into two groups based on whether they contracted the Sars-CoV-2 infection (C+) or not (C-) during the 2020/2021 season. Data collection was conducted using the Transfermarkt24 site. Results, In the 2019-2020 both championships showed non-significant differences in the average number of muscular injuries between the C+ group and the C- group (Serie A: p=0.194; 95%CI: -0.044 to 0.215, LaLiga p=0.915; 95%CI: -0.123 to 0.137). In the 2020-2021 the C+ group had a significantly higher number of muscular injuries compared to the C- group in both championships (Serie A: p<0.001; 95%CI 0.731 to 1.038; LaLiga: p<0.001; 95%CI: 0.773 to 1.054). Multiple linear regression analysis confirmed that belonging to C+ in the season 2020/2021 was the variable that most strongly influenced the probability of having a muscle injury in both championships. Survival analysis revealed a hazard ratio of 3.73 (95%CI 3.018 to 4.628) and of 5.14 (95% CI 3.200 to 8.254) for Serie A and LaLiga respectively. Conclusions This retrospective cohort study revealed a significant association between SARS-CoV-2 infection and increased risk of muscle injury, emphasizing the importance of carefully considering the infection in the decision-making process for determining athletes9 readiness to return to sport.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.11.23287138v1" target="_blank">How long is the long COVID? a retrospective analysis of football players in two major European Championships.</a>
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<li><strong>The cost of primary care consultations associated with long COVID in non-hospitalised patients: a retrospective cohort study using UK primary care data</strong> -
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Background: Over 2 million people in the UK self-reported long COVID (symptoms continuing >12 weeks after the first COVID-19 infection) as of December 2022. Long COVID can lead to significant patient burden; however, the economic impact of managing long COVID in primary care is unknown. Objectives: To assess incremental costs of primary care consultations associated with post-Covid-19 condition or long COVID, to estimate associated national costs for the United Kingdom population, and to assess risk factors associated with increased costs. Design: A retrospective cohort study using a propensity score matching approach with an incremental cost method to estimate primary care consultation costs associated with long COVID. Setting: UK-based primary care general practitioner (GP), nurse and physiotherapist consultation data from the Clinical Practice Research Datalink Aurum primary care database from 31st January 2020 to 15th April 2021. Participants: 472,173 non-hospitalised adults with confirmed SARS-CoV-2 infection were 1:1 propensity score matched to a pool of eligible patients with the same index date, the same number of prior consultations, and similar background characteristics, but without a record of COVID-19. Patients diagnosed with Long COVID (3,871) and those with World Health Organisation (WHO) defined symptoms of long COVID (30,174) formed two subgroups within the cohort with confirmed SARS-CoV-2 infection. Methods: Costs were calculated using a bottom-up costing approach with consultation cost per working hour in the British pound sterling (GBP) obtained from the Personal Social Services Research Unit, Unit Costs of Health and Social Care 2021. The average incremental cost in comparison to patients with no record of COVID-19 was produced for each patient group, considering only consultation costs at least 12 weeks from the SARS-CoV-2 infection date or matched date for the comparator group (from 15th April 2020 to 15th April 2021). A sensitivity analysis was undertaken which restricted the study population to only those who had at least 24 weeks of follow-up. National costs were estimated by extrapolating incremental costs to the cumulative incidence of COVID-19 in the UK Office for National Statistics COVID-19 Infection Survey. The impacts of risk factors on the cost of consultations beyond 12 weeks from SARS-CoV-2 infection were assessed using an econometric ordinary least squares (OLS) regression model, where coefficients were interpreted as the percentage change in cost due to a unit increase in the specific factor. Results The incremental cost of primary care consultations potentially associated with long COVID was 2.44 GBP per patient with COVID-19 per year. This increased to 5.72 GBP in the sensitivity analysis. Extrapolating this to the UK population produced a cost estimate of 23,382,452 GBP (90% credible interval: 21,378,567 GBP to 25,526,052 GBP) or 54,814,601 GBP (90% credible interval: 50,116,967 GBP to 59,839,762 GBP) in the sensitivity analysis. Among patients with COVID-19 infection, a long COVID diagnosis and longer-term reporting of symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age (49% relative increase in costs in those aged 80 years or older compared to those aged 18 to 29 years), female sex (4% relative increase in costs compared to males), obesity (4% relative increase in costs compared to those of normal weight), comorbidities and the number of prior consultations were all associated with an increase in the cost of primary care consultations. By contrast, those from black ethnic groups had a 6% reduced relative cost compared to those from white ethnic groups. Conclusions: The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.12.23287049v1" target="_blank">The cost of primary care consultations associated with long COVID in non-hospitalised patients: a retrospective cohort study using UK primary care data</a>
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<li><strong>Pulmonary sequelae at six months in children with SARS-CoV-2 infection: A Single-Centre Study</strong> -
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Objective: Pulmonary sequelae post SARS - CoV-2 infection have been reported in adults; however, there is scant literature regarding pulmonary dysfunction following SARS-CoV-2 infection in children. We studied the long term pulmonary sequelae in children who had SARS-CoV-2 infection. Methods: This single center descriptive study conducted in a public sector tertiary care hospital in Northern India, from June, 2020 to October, 2021. We enrolled children aged 7-18 years admitted with SARS-CoV-2 infection and followed them up for 6 months. A detailed interval history was taken and pulmonary function tests were performed after 6 months, using a spirometer. A convenience sample of 40 children was enrolled. There were 21 males and the median (IQR) age was 13 (10.75, 17) years. Results: Thirty percent of children (n=12) had pulmonary function abnormalities, which was of restrictive pattern in all. Children who were underweight had higher odds of developing pulmonary dysfunction following SARS-CoV-2 infection [OR (95% CI) 5.13 (1.19, 22.11); P=0.028]. There were no significant association with age, sex, severity of initial infection and oxygen requirement during the initial infection. Three children had persistence of dyspnea during follow up. Conclusion: This study is the one of the first Indian studies regarding the pulmonary sequelae in children. A possibility of long term sequelae should be considered in children with history of SARS-CoV-2, presenting with suggestive complaints.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.10.23286644v1" target="_blank">Pulmonary sequelae at six months in children with SARS-CoV-2 infection: A Single-Centre Study</a>
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<li><strong>Associations among anxiety, risk perception, preventive behaviors, and personality in Japanese older adults aged 78 to 99 years during the COVID-19 pandemic</strong> -
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Background and Objectives: To deepen the understanding of processes underlying older adults’ behavior during the COVID-19 pandemic, we investigated associations among affective (anxiety about the coronavirus), cognitive (perceived risk of infection and fatality), and behavioral (engagement in preventive behaviors) variables. We also examined how these variables were predicted by personality traits measured before the pandemic. Research Design and Methods: Older adults (N = 1,727; 78–99 years old) were recruited from an ongoing longitudinal cohort study started in 2010. They responded to a questionnaire sent in August 2020, which included four items measuring COVID-19 anxiety, infection risk perception, fatality risk perception, and engagement in preventive behaviors. Big Five personality traits were measured years ago when the participants had first participated in the study. Results: Most participants felt anxious, engaged in preventive behaviors, and overestimated infection and fatality risks. Older age was associated with low anxiety, a low perception of infection risk, a high perception of fatality risk, and a little engagement in preventive behaviors. Women were more susceptible to the pandemic than men were, demonstrated by higher scores on all four items. Partial correlation analysis controlling for age and sex demonstrated positive associations among all four items except for infection risk perception and preventive behaviors. Anxiety and perceived infection risk were positively predicted by neuroticism and conscientiousness, respectively. Engagement in preventive behaviors was positively predicted by extraversion, openness to experience, and conscientiousness. Discussion and Implications: We highlighted the critical distinction between infection and fatality risk perceptions and demonstrated the need to consider each individual’s attributes.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/vzgcp/" target="_blank">Associations among anxiety, risk perception, preventive behaviors, and personality in Japanese older adults aged 78 to 99 years during the COVID-19 pandemic</a>
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<li><strong>Genomic surveillance reveals circulation of multiple variants and lineages of SARS-CoV-2 during COVID-19 pandemic in Indian city of Bengaluru</strong> -
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Genomic surveillance in response to coronavirus disease (COVID-19) pandemic is crucial for tracking spread, identify variants of concern (VoCs) and understand the evolution of its etiological agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). India has experienced three waves of COVID-19 cases, which includes a deadly wave of COVID-19 that was driven by the Delta lineages (second/Delta wave) followed by another wave driven by the Omicron lineages (third/Omicron wave). These waves were particularly dramatic in the metropolitan cities due to high population density. We evaluated the prevalence, and mutational spectrum of SARS-CoV-2 variants/lineages in one such megapolis, Bengaluru city, across these three waves between October 2020 and June 2022. 15,134 SARS-CoV-2 samples were subjected to whole genome sequencing (WGS). Phylogenetic analysis revealed, SARS-CoV-2 variants in Bengaluru city belonged to 18 clades and 196 distinct lineages. As expected, the Delta lineages were the most dominant lineages during the second wave of COVID-19. The Omicron lineage BA.2 and its sublineages accounted for most of the COVID-19 cases in the third wave. Most number of amino acid changes were observed in spike protein. Among the 18 clades, majority of the mutations and least similarity at nucleotide sequence level with the reference genome were observed in Omicron clades.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.14.532352v1" target="_blank">Genomic surveillance reveals circulation of multiple variants and lineages of SARS-CoV-2 during COVID-19 pandemic in Indian city of Bengaluru</a>
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<li><strong>Inhibition of SARS-CoV-2 3CLpro in vitro by chemically modified tyrosinase from Agaricus bisporus</strong> -
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Antiviral compounds are crucial to controlling the SARS-CoV-2 pandemic. Approved drugs have been tested for their efficacy against COVID-19, and new pharmaceuticals are being developed as a complementary tool to vaccines However, there are not any effective treatment against this disease yet. In this work, a cheap and fast purification method of natural tyrosinase from Agaricus bisporus fresh mushrooms was developed in order to evaluate the potential of this enzyme as a therapeutic protein by the inhibition of SARS-CoV-2 3CLpro protease activity in vitro. Tyrosinase showed a mild inhibition of 3CLpro of around 15%. Thus, different variants of this protein were synthesized through chemical modifications, covalently binding different tailor-made glycans and peptides to the amino terminal groups of the protein. These new tyrosinase conjugates were purified and characterized by circular dichroism and fluorescence spectroscopy analyses, and their stability under different conditions. Then all these tyrosinase conjugates were tested in 3CLpro protease inhibition. From them, the conjugate between tyrosinase and dextran-aspartic acid (6kDa) polymer showed the highest inhibition, with an IC50 of 2.5 ug/ml and IC90 of 5 ug/ml, results that highlight the potential use of modified tyrosinase as a therapeutic protein and opens the possibility of developing this and other enzymes as pharmaceutical drugs against diseases.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.13.532357v1" target="_blank">Inhibition of SARS-CoV-2 3CLpro in vitro by chemically modified tyrosinase from Agaricus bisporus</a>
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<li><strong>SARS-CoV-2 N-protein induces the formation of composite α-synuclein/N-protein fibrils that transform into a strain of α-synuclein fibrils</strong> -
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The presence of deposits of alpha-synuclein fibrils in cells of the brain are a hallmark of several -synucleinopathies, including Parkinson’s disease. As most disease cases are not familial, it is likely that external factors play a role in disease onset. One of the external factors that may influence disease onset are viral infections. It has recently been shown that in the presence of SARS-Cov-2 N-protein, S fibril formation is faster and proceeds in an unusual two-step aggregation process. Here, we show that faster fibril formation is not due to a SARS-CoV-2 N-protein-catalysed formation of an aggregation-prone nucleus. Instead, aggregation starts with the formation of a population of mixed S/N-protein fibrils with low affinity for S. After the depletion of N-protein, fibril formation comes to a halt, until a slow transformation to fibrils with characteristics of pure S fibril strains occurs. This transformation into a strain of S fibrils subsequently results in a second phase of fibril growth until a new equilibrium is reached. Our findings point at the possible relevance of fibril strain transformation in the cell-to-cell spread of the S pathology and disease onset.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.13.532385v1" target="_blank">SARS-CoV-2 N-protein induces the formation of composite α-synuclein/N-protein fibrils that transform into a strain of α-synuclein fibrils</a>
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<li><strong>Correlating physicochemical and biological properties to define critical quality attributes of a recombinant AAV vaccine candidate</strong> -
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Recombinant adeno-associated viruses (rAAVs) are a preferred vector system in clinical gene transfer. A fundamental challenge to formulate and deliver rAAVs as stable and efficacious vaccines is to elucidate interrelationships between the vectors physicochemical properties and biological potency. To this end, we evaluated an rAAV-based COVID-19 vaccine candidate which encodes the Spike antigen (AC3) and is produced by an industrially-compatible process. First, state-of-the-art analytical techniques were employed to determine key structural attributes of AC3 including primary and higher-order structures, particle size, empty/full capsid ratios, aggregates and multi-step thermal degradation pathway analysis. Next, several quantitative potency measures for AC3 were implemented and data were correlated with the physicochemical analyses on thermal-stressed and control samples. Results demonstrate links between decreasing AC3 physical stability profiles, in vitro transduction efficiency in a cell-based assay, and importantly, in vivo immunogenicity in a mouse model. These findings are discussed in the general context of future development of rAAV-based vaccines candidates as well as specifically for the rAAV vaccine application under study.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.10.532114v1" target="_blank">Correlating physicochemical and biological properties to define critical quality attributes of a recombinant AAV vaccine candidate</a>
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<li><strong>Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals</strong> -
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The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to public health. Besides humans, SARS-CoV-2 can infect several animal species. Highly sensitive and specific diagnostic reagents and assays are urgently needed for rapid detection and implementation of strategies for prevention and control of the infection in animals. In this study, we initially developed a panel of monoclonal antibodies (mAbs) against SARS-CoV-2 nucleocapsid (N) protein. To detect SARS-CoV-2 antibodies in a broad spectrum of animal species, a mAb-based bELISA was developed. Test validation using a set of animal serum samples with known infection status obtained an optimal percentage of inhibition (PI) cut-off value of 17.6% with diagnostic sensitivity of 97.8% and diagnostic specificity of 98.9%. The assay demonstrates high repeatability as determined by a low coefficient of variation (7.23%, 6.95%, and 5.15%) between-runs, within-run, and within-plate, respectively. Testing of samples collected over time from experimentally infected cats showed that the bELISA was able to detect seroconversion as early as 7 days post-infection. Subsequently, the bELISA was applied for testing pet animals with COVID-19-like symptoms and specific antibody responses were detected in two dogs. The panel of mAbs generated in this study provides a valuable tool for SARS-CoV-2 diagnostics and research. The mAb-based bELISA provides a serological test in aid of COVID-19 surveillance in animals.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.11.532204v1" target="_blank">Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals</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>Use of E-health Based Exercise Intervention After COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Exercise training using an e-health tool<br/><b>Sponsors</b>: Norwegian University of Science and Technology; University of Oslo<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>Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)<br/><b>Sponsor</b>: WestVac 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>A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant variant COVID-19 vaccine (Sf9 cell); Biological: Recombinant COVID-19 vaccine (CHO cell); Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>: WestVac 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>A Study to Compare QLS1128 With Placebo in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu Pharmaceutical 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>Effect of Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Other: Pursed lip breathing; Other: Cognitive Behavior Therapy; Other: Diaphragmatic breathing exercise; Other: Kinesio tape<br/><b>Sponsor</b>: Cairo 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>Effect of Selected Types of Breathing Exercises on Different Outcome Measures in Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: breathing exercise<br/><b>Sponsor</b>: Basma Mosaad Abd-elrahman Abushady<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Calcitriol; Other: Placebo<br/><b>Sponsor</b>: Universitas Sebelas Maret<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: P1101 (Ropeginterferon alfa-2b); Procedure: SOC<br/><b>Sponsor</b>: National Taiwan University Hospital<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>Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine</strong> - <b>Conditions</b>: Vaccine Reaction; COVID-19<br/><b>Interventions</b>: Biological: Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech); Biological: VidPrevtyn® Beta vaccine (Sanofi/GSK)<br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of WPV01 Compared With Placebo in Patients With Mild/Moderate COVID-19 Infection</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo<br/><b>Sponsor</b>: Westlake Pharmaceuticals (Hangzhou) 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>Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)</strong> - <b>Conditions</b>: Covid19; Hydrogen-oxygen Gas; AMS-H-03<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Device: OLO-1 Medical Molecular Sieve Oxygen Generator<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ARVAC-A New Recombinant Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: Gamma Variant RBD-based ARVAC-CG vaccine; Biological: Omicron Variant RBD-based ARVAC-CG vaccine; Biological: Bivalent RBD-based ARVAC-CG vaccine; Other: Placebo<br/><b>Sponsors</b>: Mónica Edith Lombardo; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina; Laboratorio Pablo Cassará S.R.L.<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>Oxygen Atomizing Inhalation of EGCG in the Treatment COVID-19 Pneumonia in Cancer Patients</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Neoplasms Malignant<br/><b>Interventions</b>: Drug: EGCG; Drug: Placebo<br/><b>Sponsor</b>: Shandong Cancer Hospital and Institute<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Use of Photobiomodulation in the Treatment of Oral Complaints of Long COVID-19.A Randomized Controlled Trial.</strong> - <b>Conditions</b>: Xerostomia; COVID-19; Long COVID; Persistent COVID-19<br/><b>Interventions</b>: Combination Product: Institutional standard treatment for xerostomia and Long Covid; Radiation: Photobiomodulation Therapy; Radiation: Placebo Photobiomodulation Therapy<br/><b>Sponsor</b>: University of Nove de Julho<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Acupuncture for Post COVID-19 Fatigue</strong> - <b>Conditions</b>: Acupuncture; Post COVID-19 Condition; Fatigue<br/><b>Interventions</b>: Device: Acupuncture; Device: Sham Acupuncture<br/><b>Sponsor</b>: Guang’anmen Hospital of China Academy of Chinese Medical Sciences<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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Delivery of anti-microRNA-21 by lung-targeted liposomes for pulmonary fibrosis treatment</strong> - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder with a low survival rate. Pulmonary fibrosis is one of the complications of COVID-19 and has a high prevalence in COVID-19 patients. Currently, no effective therapies other than lung transplantation are available to cure IPF and post-COVID-19 pulmonary fibrosis. MicroRNAs are small non-coding RNAs that mediate the development and progression of pulmonary fibrosis, thus making them potent drug candidates for this serious disease….</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>Insights of different analytical approaches for estimation of budesonide as COVID-19 replication inhibitor in its novel combinations: green assessment with AGREE and GAPI approaches</strong> - Simple, direct, rapid, and sensitive HPLC and spectrophotometric methods were established for simultaneous estimation of a novel combination of budesonide and azelastine (BUD/AZL) in their laboratory-prepared mixture and dosage form according to the medicinally recommended ratio 1:4.28. Budesonide is an important inhalation corticosteroid that plays a vital role in the inhibition of COVID-19 replication and cytokine production. The first chromatographic method was created for the simultaneous…</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 multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection</strong> - COVID-19 is a systemic disease involving multiple organs. We previously established a platform to derive organoids and cells from human pluripotent stem cells to model SARS-CoV-2 infection and perform drug screens^(1,2). This provided insight into cellular tropism and the host response, yet the molecular mechanisms regulating SARS-CoV-2 infection remain poorly defined. Here we systematically examined changes in transcript profiles caused by SARS-CoV-2 infection at different multiplicities of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients</strong> - CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the ‘cytokine storm’ in 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>Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors</strong> - The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopeptide antibiotics teicoplanin derivatives that bind to the SARS-CoV-2 spike (S) protein, interrupt its interaction with ACE2 receptor and selectively inhibit viral entry mediated by S protein….</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>Paving New Roads Using <em>Allium sativum</em> as a Repurposed Drug and Analyzing its Antiviral Action Using Artificial Intelligence Technology</strong> - CONCLUSIONS: The COVID-19 pandemic has triggered interest among researchers to conduct future research on molecular docking with clinical trials before releasing salutary remedies against the deadly malady.</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>Brevicillin, a novel lanthipeptide from the genus Brevibacillus with antimicrobial, antifungal and antiviral activity</strong> - CONCLUSION: This study provides detailed description of a novel lanthipeptide and demonstrates its effective antibacterial, antifungal and anti-SARS-CoV-2 activity.</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 residual humoral immune response against SARS-CoV-2 by a surrogate virus neutralization test (sVNT) 9 months after BNT162b2 primary vaccination</strong> - The humoral response to SARS-CoV-2 vaccination has shown to be temporary, although may be more prolonged in vaccinated individuals with a history of natural infection. We aimed to study the residual humoral response and the correlation between anti-Receptor Binding Domain (RBD) IgG levels and antibody neutralizing capacity in a population of health care workers (HCWs) after 9 months from COVID-19 vaccination. In this cross-sectional study, plasma samples were screened for anti-RBD IgG using a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2</strong> - Gemcitabine is a nucleoside analogue of deoxycytidine and has been reported to be a broad-spectrum antiviral agent against both DNA and RNA viruses. Screening of a nucleos(t)ide analogue-focused library identified gemcitabine and its derivatives (compounds 1, 2a, and 3a) blocking influenza virus infection. To improve their antiviral selectivity by reducing cytotoxicity, 14 additional derivatives were synthesized in which the pyridine rings of 2a and 3a were chemically modified….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A novel mAb broadly neutralizes SARS-CoV-2 VOCs in vitro and in vivo, including the Omicron variants</strong> - Novel immune escape variants have emerged as SARS-CoV-2 continues to spread worldwide. Many of the variants cause breakthrough infections in vaccinated populations, posing great challenges to current antiviral strategies targeting the immunodominance of the receptor-binding domain within the spike protein. Here, we found that a novel broadly neutralizing monoclonal antibody (mAb), G5, provided efficient protection against SARS-CoV-2 variants of concern (VOCs) in vitro and in vivo. A single dose…</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>Mucosal immunization with Ad5-based vaccines protects Syrian hamsters from challenge with omicron and delta variants of SARS-CoV-2</strong> - SARS-CoV-2 variant clades continue to circumvent antibody responses elicited by vaccination or infection. Current parenteral vaccination strategies reduce illness and hospitalization, yet do not significantly protect against infection by the more recent variants. It is thought that mucosal vaccination strategies may better protect against infection by inducing immunity at the sites of infection, blocking viral transmission more effectively, and significantly inhibiting the evolution of new…</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>2-Deoxy-D-Glucose: A Novel Pharmacological Agent for Killing Hypoxic Tumor Cells, Oxygen Dependence-Lowering in Covid-19, and Other Pharmacological Activities</strong> - The nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) has shown promising pharmacological activities, including inhibition of cancerous cell growth and N-glycosylation. It has been used as a glycolysis inhibitor and as a potential energy restriction mimetic agent, inhibiting pathogen-associated molecular patterns. Radioisotope derivatives of 2-DG have applications as tracers. Recently, 2-DG has been used as an anti-COVID-19 drug to lower the need for supplemental oxygen. In the present…</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>Potential Regulation of NF-κB by Curcumin in Coronavirus-Induced Cytokine Storm and Lung Injury</strong> - The current pandemic coronavirus disease-19 (COVID-19) is still a global medical and economic emergency with over 244 million confirmed infections and over 4.95 million deaths by October 2021, in less than 2 years. Severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome coronavirus (MERS), and COVID-19 are three recent coronavirus pandemics with major medical and economic implications. Currently, there is no effective treatment for these infections. One major pathological…</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>Type I interferon signaling induces a delayed antiproliferative response in Calu-3 cells during SARS-CoV-2 infection</strong> - Disease progression during SARS-CoV-2 infection is tightly linked to the fate of lung epithelial cells, with severe cases of COVID-19 characterized by direct injury of the alveolar epithelium and an impairment in its regeneration from progenitor cells. The molecular pathways that govern respiratory epithelial cell death and proliferation during SARS-CoV-2 infection, however, remain poorly understood. We now report a high-throughput CRISPR screen for host genetic modifiers of the survival 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>Induction of systemic, mucosal, and cellular immunity against SARS-CoV-2 in mice vaccinated by trans-airway with a S1 protein combined with a pulmonary surfactant-derived adjuvant SF-10</strong> - CONCLUSIONS: Based on the need for effective systemic, respiratory, and cellular immunity, the S1-SF-10-TA vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.</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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