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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>16 May, 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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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Metformin an anti-diabetic drug, possess ACE-2 receptor-SARS- Cov-2 RBD binding antagonist activity, anti-inflammatory and cytokine inhibitory properties suitable for treatment of COVID-19</strong> -
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Metformin is a widely used and is a safe anti-diabetic drug. It has also been shown to have anti-inflammatory and anti-viral activities in humans and animal models. Specifically we explored its activity in SARS-CoV-2 initiated COVID19 disease. Here we show that metformin 1. blocks the binding of SARS-CoV-2 spike protein receptor binding domain RBD to human ACE2 receptor 2. We also show that it has anti-inflammatory effects and reduces cytokine secretion as well as blocks the recruitment of monocytes to endothelial cells 3. Finally we show its activity in a hamster in vivo model of SARS-CoV-2 infection as a nasal formulation. Based on the safety and the therapeutic properties relevant to COVID-19 it is feasible to propose a nasal spray of metformin that can be used in treatment of this disease. A nasal spray would deliver the drug to the target organ lung and spare other organs which get exposed upon oral dosing.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.14.540726v1" target="_blank">Metformin an anti-diabetic drug, possess ACE-2 receptor-SARS- Cov-2 RBD binding antagonist activity, anti-inflammatory and cytokine inhibitory properties suitable for treatment of COVID-19</a>
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<li><strong>A peptide derived from the SARS-CoV-2 S2-protein heptad-repeat-2 inhibits pseudoviral fusion at micromolar concentrations: Role of palmitic acid conjugation</strong> -
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SARS-CoV-2 S protein-mediated fusion is thought to involve the interaction of the membrane-distal, or N-terminal heptad repeat (NHR) (termed HR1) of the cleaved S2 segment of the protein, and the membrane-proximal, or C-terminal heptad repeat (CHR) (termed HR2) regions of the protein. Following the observations of Xia et al (Xia S, Liu M, Wang C, Xu W, Lan Q, Feng S, Qi F, Bao L, Du L, Liu S, Qin C, Sun F, Shi Z, Zhu Y, Jiang S, Lu L. Cell Res. 2020b Apr;30(4):343-355), we examined the fusion inhibitory activity of a PEGylated HR2-derived peptide and its palmitoylated derivative, using a pseudovirus infection assay. The latter peptide caused a 76% reduction in fusion activity at 10 M. Our results suggest that small variations in peptide derivatization and differences in the membrane composition of pseudovirus preparations may affect the inhibitory potency of HR2-derived peptides.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.13.540576v1" target="_blank">A peptide derived from the SARS-CoV-2 S2-protein heptad-repeat-2 inhibits pseudoviral fusion at micromolar concentrations: Role of palmitic acid conjugation</a>
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</div></li>
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<li><strong>Reconstructing the first COVID-19 pandemic wave with minimal data in the UK</strong> -
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Accurate measurement of exposure to SARS-CoV-2 in the population is crucial for understanding the dynamics of disease transmission and evaluating the impacts of interventions. However, it is particularly challenging to achieve this in the early phase of a pandemic because of the sparsity of epidemiological data. In our previous publication [1], we developed an early pandemic diagnostic tool that can link minimum datasets: seroprevalence, mortality and infection testing data to estimate the true exposure in different regions of England and found levels of SARS-CoV-2 population exposure are considerably higher than suggested by seroprevalence surveys. Here, we re-examined and evaluated the model in the context of reconstructing the first COVID-19 epidemic wave in England from three perspectives: validation from ONS Coronavirus Infection Survey, relationship between model performance and data abundance and time-varying case detection rate. We found that our model can recover the first but unobserved epidemic wave of COVID-19 in England from March 2020 to June 2020 as long as two or three serological measurements are given as model inputs additionally, with the second wave during winter of 2020 validated by the estimates from ONS Coronavirus Infection Survey. Moreover, the model estimated that by the end of October in 2020 the UK governments official COVID-9 online dashboard reported COVID-19 cases only accounted for 9.1% (95%CrI (8.7%,9.8%)) of cumulative exposure, dramatically varying across two epidemic waves in England in 2020 (4.3% (95%CrI (4.1%, 4.6%)) vs 43.7% (95%CrI (40.7%, 47.3%))).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.17.23287140v2" target="_blank">Reconstructing the first COVID-19 pandemic wave with minimal data in the UK</a>
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<li><strong>Lip movements and lexical features improve speech tracking differently for clear and multi-speaker speech</strong> -
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Visual speech plays a powerful role in facilitating auditory speech processing and has been a publicly noticed topic with the wide usage of face masks during the Covid-19 pandemic. In a previous magnetoencephalography (MEG) study we showed that occluding the mouth area significantly impairs neural speech tracking. To rule out the possibility that this deterioration is due to degraded sound quality, in the present follow-up study, we presented participants with audiovisual (AV) and audio-only (A) speech. We further independently manipulated the trials by adding a face mask and a distractor speaker. Our results clearly show that face masks only affect speech tracking in AV conditions, not in A conditions. This shows that face masks indeed primarily impact speech processing by blocking visual speech and not by acoustic degradation. Furthermore, we observe differences in the speech features that are used for visual speech processing. On the one hand, processing in clear speech, but not in noisy speech, is profiting more from lexical unit features (phonemes and word onsets) hinting at improved phoneme discrimination. On the other hand, we observe an improvement in speech tracking driven by the modulations of the lip area in clear speech and conditions with a distractor speaker, which might aid by providing temporal cues for subsequent auditory processing. With this work, we highlight the effects of face masks in AV speech tracking and show two separate ways how visual speech might support successful speech processing.
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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/10.1101/2023.05.15.540818v1" target="_blank">Lip movements and lexical features improve speech tracking differently for clear and multi-speaker speech</a>
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<li><strong>Ability to detect fake news predicts sub-national variation in COVID-19 vaccine uptake across the UK</strong> -
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Susceptibility to believing false or misleading information is associated with a range of adverse outcomes. However, it is notoriously difficult to study the link between susceptibility to misinformation and consequential real-world behaviors such as vaccine uptake. In this preregistered study, we devise a large-scale socio-spatial model that combines the rigor of a psychometrically validated test of misinformation susceptibility administered to a nationally representative sample of 16,477 individuals with COVID-19 vaccine uptake data of 129 sub-national regions published by the United Kingdom (UK) government, to show that the general ability to detect misinformation strongly and positively predicts regional vaccine uptake in the UK. We put this practically significant correlational effect size into perspective by noting how psychological interventions that reduce individuals9 misinformation susceptibility could be associated with additional vaccine uptake.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289764v1" target="_blank">Ability to detect fake news predicts sub-national variation in COVID-19 vaccine uptake across the UK</a>
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<li><strong>Effectiveness of drugs for COVID-19 inpatients in Japanese medical claim data as average treatment effects with inverse probability weighted regression adjustment</strong> -
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Background: Earlier studies and clinical trials have indicated that drugs such as antiviral drugs, antibody cocktails, and steroids and anti-inflammatory drugs are expected to prevent severe coronavirus disease 2019 (COVID-19) outcomes and death. Object: We used observational data for Japan to assess the effectiveness of these drugs for treating COVID-19. Method: We applied an average treatment effect model with inverse probability weighted regression adjustment, which can treat the choice of administered drug as a random assignment to inpatients, to the Medical Information Analysis Databank operated by National Hospital Organization in Japan. The outcome was defined as mortality. Subjects were all inpatients, inpatients with oxygen administration, and inpatients using respiratory ventilators, classified by three age classes: all ages, 65 years old or older, and younger than 65 years old. Information about physical characteristics, underlying disease, administered drug, the proportion of mutated strains, and vaccine coverage were used as explanatory variables for logistic regression. Result: Estimated results indicated that only an antibody cocktail (sotrovimab, casirivimab and imdevimab) raised the probability of saving life consistently, even though these drugs were administered in few cases. By contrast, other drugs might reduce the probability of saving life. Discussion: Results indicate that an antiviral drug (remdesivir), a steroid (dexamethasone), and an anti-inflammatory drug (baricitinib and tocilizumab) might not contribute to the saving of life, even in the pseudo-situation of random assignment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289913v1" target="_blank">Effectiveness of drugs for COVID-19 inpatients in Japanese medical claim data as average treatment effects with inverse probability weighted regression adjustment</a>
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<li><strong>Insight into risk associated phenotypes behind COVID-19 from phenotype genome-wide association studies</strong> -
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Long COVID presents a complex and multi-systemic disease that poses a significant global public health challenge. Symptoms can vary widely, ranging from asymptomatic to severe, making the condition challenging to diagnose and manage effectively. Furthermore, identifying appropriate phenotypes in genome-wide association studies of COVID-19 remains unresolved. This study aimed to address these challenges by analyzing 220 deep-phenotype genome-wide association data sets (159 diseases, 38 biomarkers and 23 medication usage) from BioBank Japan (BBJ) (n=179,000), UK Biobank and FinnGen (n=628,000) to investigate pleiotropic effects of known COVID-19 risk associated single nucleotide variants. Our findings reveal 32 different phenotypes that share the common genetic risk factors with COVID-19 (p < 7.6×10−11), including two diseases (myocardial infarction and type 2 diabetes), 26 biomarkers with seven categories (blood cell, metabolic, liver-related, kidney-related, protein, inflammatory and anthropometric), and four medications (antithrombotic agents, HMG CoA reductase inhibitors, thyroid preparations and anilides). As long COVID continues to coexist with humans, our results highlight the need for targeted screening to support specific vulnerable populations to improve disease prevention and healthcare delivery.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.09.23289706v1" target="_blank">Insight into risk associated phenotypes behind COVID-19 from phenotype genome-wide association studies</a>
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<li><strong>Projecting the potential impact of an Omicron XBB.1.5 wave in Shanghai, China</strong> -
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China experienced a major nationwide wave of SARS-CoV-2 infections in December 2022, immediately after lifting strict interventions, despite the majority of the population having already received inactivated COVID-19 vaccines. Due to the rapid waning of protection and the emergence of Omicron XBB.1.5, the risk of another COVID-19 wave remains high. It is still unclear whether the health care system will be able to manage the demand during this potential XBB.1.5 wave and if the number of associated deaths can be reduced to a level comparable to that of seasonal influenza. Thus, we developed a mathematical model of XBB.1.5 transmission using Shanghai as a case study. We found that a potential XBB.1.5 wave is less likely to overwhelm the health care system and would result in a death toll comparable to that of seasonal influenza, albeit still larger, especially among elderly individuals. Our analyses show that a combination of vaccines and antiviral drugs can effectively mitigate an XBB.1.5 epidemic, with a projected number of deaths of 2.08 per 10,000 individuals. This figure corresponds to a 70-80% decrease compared to the previous Omicron wave and is comparable to the level of seasonal influenza. The peak prevalence of hospital admissions and ICU admissions are projected at 28.89 and 2.28 per 10,000 individuals, respectively, suggesting the need for a moderate increase in the capacity of the health care system. Our findings emphasize the importance of improving vaccination coverage, particularly among the older population, and the use of antiviral treatments.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289761v1" target="_blank">Projecting the potential impact of an Omicron XBB.1.5 wave in Shanghai, China</a>
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<li><strong>“Now you see me”: detecting asymptomatic infectious individuals in the population</strong> -
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Quarantine is an effective countermeasure to stop or slow the spread of an emerging infectious disease when no other preventive measures are available to protect the population. However, when the disease results in a proportion of asymptomatic infections, the spread dynamics are affected, and quarantine efficiency is impaired. Here, we introduce an extended susceptible-infected-recovered (SIR) model to study the effects of asymptomatic individuals at the onset of an emerging infectious disease when no vaccination is yet available and/or when a vaccine is available but only a subset of the population can be vaccinated due to limited supply or the unwillingness of susceptible individuals to receive an injection. These aspects have been indirectly incorporated into the model using a time-dependent vaccination rate. With this model, we confirm that, in the case of a missing vaccine, quarantine is effective in stopping the spread of an infectious disease, but its efficiency can be substantially reduced in the presence of individuals developing asymptomatic infection. Moreover, we show that vaccination is effective only if available early during the epidemic and if the vaccination rate is sufficiently high. By applying this model to Zurich and all of Switzerland in case of the COVID-19 pandemic, we found that the following two strategies have similar outcomes: either placing infectious individuals into quarantine when no vaccine is available or dropping quarantine measures but administering a vaccine at a daily rate of 1%, starting no later than 105 days after the onset of the epidemic. Beyond this time period, a vaccination campaign will have no effect in stopping the spread of the disease if 25% of the susceptible population is asymptomatic. We also found that the option of deploying a vaccination campaign was more effective for all of Switzerland than for only the city of Zurich.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.08.23289685v1" target="_blank">“Now you see me”: detecting asymptomatic infectious individuals in the population</a>
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<li><strong>Immune response to SARS CoV2 infection by TLR3, TLR4 and TLR7 expression</strong> -
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Toll like receptors (TLRs) may be involved both in the initial failure of viral clearance and in the subsequent development of fatal clinical manifestations of severe COVID19, essentially ARDS (acute respiratory distress syndrome) with fatal respiratory failure. While TLR3 recognizes viral double stranded RNA (dsRNA), TLR7 recognizes viral single stranded RNA and is therefore likely to be involved in SARS CoV2 clearance. On the other hand, TLR4, at the surface of cells, toll like receptor 4 (TLR4) in the induction of damaging inflammatory responses during acute viral infections as it functions as a sensor for damage associated molecular patterns (DAMPs). These include a wide variety of molecules released from injured or dying tissues as well as molecules actively released in response to cellular stress from intact cells. We present the gene expression of TLR 3, 4, and 7 in nasopharyngeal total RNA samples from 150 individuals positive for SARS Cov2 (DET) by molecular techniques of isothermal amplification (Neokit SA) and 152 SARS CoV2 non detectable (ND) ambulatory and hospitalizedpatients with a non-defined respiratory disease, and we compared with the symptomatology developed by all those patients. We analyzed 4 cohorts: 1 SARS Cov2 genome detected patients with severe to high symptomatology (n=107);2 SARS Cov2 genome detected patients low to mild symptomatology (n=43); 3 SARS Cov2 genome non detected patients with severe to high symptomatology (n=109); and 4 SARS Cov2 genome non detected patients low to mild symptomatology (n=41). Our results showed no significant differences of expression for TLR3, TLR4 and TLR7 between SARS Cov2 detected and non-detected total cohort of patients (Non Paired T test p Value>0.1). When compared severity of symptoms (presence of symptoms from the COVID19 12 diagnosis symptoms) and gene expression by a Spearman9s Correlation Coefficient there was significant positive correlation between severe symptomatology, and the number of symptoms and death for TLR4 and TLR7 for both infected and non COVID19 infected patients. When the cohort was construct with low/middle and severe symptoms, the Correlation Coefficient showed that expression of TLR4 and TLR7 was significantly amplified in those ND patients with severe symptomatology (p Value= 0.00311) as well as for TLR3 in ND low to mild symptoms cohort of patients. We also showed and discussed the results obtained of these genes expression and the sex and age of patients. In summary, our data suggest that although our innate immune system with TLRs contributes to the elimination of viruses, it can also be associated with harm to the host due to persistent inflammation and tissue destruction. We confirmed that principally TLR4 and TLR7 could be involved not only in the pathogenesis of COVID19 but also in other respiratory diseases with same symptomatology. We suggest that treatments focus on TLR4 and TLR7 expression in inflammatory respiratory diseases could be a start point against severe symptoms development.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23288889v1" target="_blank">Immune response to SARS CoV2 infection by TLR3, TLR4 and TLR7 expression</a>
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<li><strong>From Collection to Analysis: A Comparison of GISAID and the Covid-19 Data Portal</strong> -
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We analyse ongoing efforts to share genomic data about SARS-COV-2 through a comparison of the characteristics of the Global Initiative on Sharing All Influenza Data and the Covid-19 Data Portal with respect to the representativeness and governance of the research data therein. We focus on data and metadata on genetic sequences posted on the two infrastructures in the period between January 2020 and January 2023, thus capturing a period of acute response to the COVID-19 pandemic. Through a variety of data science methods, we compare the extent to which the two portals succeeded in attracting data submissions from different countries around the globe and look at the ways in which submission rates varied over time. We go on to analyse the structure and underlying architecture of the infrastructures, reviewing how they organise data access and use, the types of metadata and version tracking they provide. Finally, we explore usage patterns of each infrastructure based on publications that mention the data to understand how data reuse can facilitate forms of diversity between institutions, cities, countries, and funding groups. Our findings reveal disparities in representation between the two infrastructures and differing practices in data governance and architecture. We conclude that both infrastructures offer useful lessons, with GISAID demonstrating the importance of expanding data submissions and representation, while the COVID-19 data portal offers insights into how to enhance data usability.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.13.540634v1" target="_blank">From Collection to Analysis: A Comparison of GISAID and the Covid-19 Data Portal</a>
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<li><strong>Large-scale template-based structural modeling of T-cell receptors with known antigen specificity reveals complementarity features.</strong> -
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T-cell receptor (TCR) recognition of foreign peptides presented by the major histocompatibility complex (MHC) initiates the adaptive immune response against pathogens. A large number of TCR sequences specific to different antigens are known to date, however, the structural data describing the conformation and contacting residues for TCR:antigen:MHC complexes is relatively limited. In the present study we aim to extend and analyze the set of available structures by performing highly accurate template-based modeling of TCR:antigen:MHC complexes using TCR sequences with known specificity. Using the set of 29 complex templates (including a template with SARS-CoV-2 antigen) and 732 specificity records, we built a database of 1585 model structures carrying substitutions in either TCR or TCR{beta} chains with some models representing the result of different mutation pathways for the same final structure. This database allowed us to analyze features of amino acid contacts in TCR:antigen interfaces that govern antigen recognition preferences and interpret these interactions in terms of physicochemical properties of interacting residues. Our results provide a methodology for creating high-quality TCR:antigen:MHC models for antigens of interest that can be utilized to predict TCR specificity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.29.533758v3" target="_blank">Large-scale template-based structural modeling of T-cell receptors with known antigen specificity reveals complementarity features.</a>
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<li><strong>Moving online: Experiences and potential benefits of digital dance for older adults and individuals with Parkinson’s disease</strong> -
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Background. Dance is found to provide a range of beneficial effects for older adults including individuals with age-related neurological conditions such as Parkinson’s disease (PD). The COVID-19 pandemic accelerated the development of at-home dance programs delivered digitally through live and pre-recorded media, but little is known about how participants may engage with and benefit from these resources. Objective. This study explored experiences and potential benefits of digital dance resources among healthy older adults and individuals with neurological conditions. Methods. An online survey consisting of fixed-choice and open questions was designed in collaboration with dance program providers and distributed between June and November 2020. Results. High levels of engagement in at-home dance programs were found among healthy older adults (N = 149) and individuals with PD (N = 178). Sensorimotor outcomes (e.g., balance, posture) were more widely reported among individuals with PD, while older adults reported similar numbers of sensorimotor and non-motor (e.g., mood, confidence) outcomes. The use of strategies (imagery and vocalising) during participation were differentially associated with outcomes in older adults and PD groups. At-home dance was found to offer convenience and flexibility, but participants missed the interaction, support and routine of in-person classes. The majority expressed a preference to continue with both digital and in-person participation in the future. Qualitative analysis of participants’ comments reinforced the quantitative findings, while also revealing that online dance could help to maintain connection and well-being, and identifying further considerations for improving accessibility and facilitating digital engagement. Conclusions. At-home dance programs appear to be accessible and engaging for older adults, including individuals with PD, although potential barriers to participation need to be addressed. Digital resources for home-based activities will be increasingly important to enable cost-effective, large-scale provision of therapeutic activities for older adults.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/954f2/" target="_blank">Moving online: Experiences and potential benefits of digital dance for older adults and individuals with Parkinson’s disease</a>
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<li><strong>Dance at home for people with Parkinson’s during COVID-19 and beyond: Participation, perceptions and prospects</strong> -
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Emerging evidence shows that dance can provide both physical and non-physical benefits for people living with Parkinson’s disease (PD). The suspension of in-person dance classes during the COVID-19 pandemic necessitated a transition to remote provision via live and recorded digital media. An online survey explored accessibility of and engagement with these home-based dance programs, as well as perceived benefits. The survey was co-developed by researchers and dance program providers, with input from people with PD and physiotherapists. Responses were collected from 276 individuals, including 178 current users of home-based programs, the majority of whom were participating at least once per week. Among respondents not currently using digital resources, lack of knowledge and motivation were the primary barriers. Most participants (94.9%) reported that home based practice provided some benefits, including physical (e.g., balance, posture) and non-physical (e.g., mood, confidence) improvements. Participants valued the convenience and flexibility of digital participation, but noted limitations including reductions in social interaction, support from instructors and peers, and routine. There was a strong preference (70.8%) for continuing with home-based practice alongside in-person classes in the future. The results indicate that at-home dance is accessible and usable for people with PD, and that some of the previously-reported benefits of dance may be replicated in this context. While COVID-19 expedited the development of digital programs, these will likely remain a key element of future provision for people with PD. The findings will inform the further development of resources and research into outcomes of home-based dance participation.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/4wep9/" target="_blank">Dance at home for people with Parkinson’s during COVID-19 and beyond: Participation, perceptions and prospects</a>
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<li><strong>Regulation of coronavirus nsp15 cleavage specificity by RNA structure</strong> -
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SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, has had an enduring impact on global public health. However, SARS-CoV-2 is only one of multiple pathogenic human coronaviruses (CoVs) to have emerged since the turn of the century. CoVs encode for several nonstructural proteins (NSPS) that are essential for viral replication and pathogenesis. Among them is nsp15, a uridine-specific viral endonuclease that is important in evading the host immune response and promoting viral replication. Despite the established function of nsp15 as a uridine-specific endonuclease, little is known about other determinants of its cleavage specificity. In this study we investigate the role of RNA secondary structure in SARS-CoV-2 nsp15 endonuclease activity. Using a series of in vitro endonuclease assays, we observed that thermodynamically stable RNA structures were protected from nsp15 cleavage relative to RNAs lacking stable structure. We leveraged the s2m RNA from the SARS 3'UTR as a model for our structural studies as it adopts a well-defined structure with several uridines, two of which are unpaired and thus high probably targets for nsp15 cleavage. We found that SARS-CoV-2 nsp15 specifically cleaves s2m at the unpaired uridine within the GNRNA pentaloop of the RNA. Further investigation revealed that the position of uridine within the pentaloop also impacted nsp15 cleavage efficiency, suggesting that positioning within the pentaloop is necessary for optimal presentation of the scissile uridine and alignment within the nsp15 catalytic pocket. Our findings indicate that RNA secondary structure is an important determinant of nsp15 cleavage and provides insight into the molecular mechanisms of recognition of RNA by nsp15.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.12.540483v1" target="_blank">Regulation of coronavirus nsp15 cleavage specificity by RNA structure</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>The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Glucocorticoid<br/><b>Sponsor</b>: Huashan Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Arginine Replacement Therapy in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Arginine Hydrochloride<br/><b>Sponsor</b>: Emory 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>Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Intramuscularly administered Ad5-nCoV vaccine; Biological: Aerosolized Ad5-nCoV; Biological: DelNS1-2019-nCoV-RBD-OPT1; Biological: SYS6006<br/><b>Sponsor</b>: Jiangsu Province Centers for Disease Control and Prevention<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 Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment</strong> - <b>Condition</b>: Post COVID-19 Cognitive Impairment<br/><b>Interventions</b>: Device: Vielight Neuro RX Gamma active device; Device: Vielight Neuro RX Gamma sham device<br/><b>Sponsor</b>: Vielight 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>Working Towards Empowered Community-driven Approaches to Increase Vaccination and Preventive Care Engagement</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: mHealth Outreach; Other: Care Coordination<br/><b>Sponsors</b>: University of California, San Diego; San Ysidro Health Center<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway</strong> - <b>Conditions</b>: Post COVID-19 Condition, Unspecified; SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Drug: Nirmatrelvir/ritonavir; Drug: Placebo<br/><b>Sponsors</b>: Haukeland University Hospital; University of Bergen<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>Role of Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Vitamin-D<br/><b>Sponsor</b>: Sulaimany Polytechnic 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>REVERSE-Long COVID-19 With Baricitinib Pilot Study</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Drug: Baricitinib 4 MG<br/><b>Sponsors</b>: Vanderbilt University Medical Center; Emory University; University of California, San Francisco; University of Minnesota; Vanderbilt University; Yale 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>Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Dysautonomia<br/><b>Interventions</b>: Procedure: Rehabilitation; Procedure: Standard of Care<br/><b>Sponsors</b>: Evangelismos Hospital; National and Kapodistrian University of Athens; LONG COVID GREECE; 414 Military Hospital of Special Diseases<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>Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention</strong> - <b>Condition</b>: Sars-CoV-2 Infection<br/><b>Interventions</b>: Drug: Alveavax-v1.2; Drug: Janssen Ad26.COV2.S<br/><b>Sponsor</b>: Alvea Holdings, LLC<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Vaccination Detoxification in LDL-C</strong> - <b>Conditions</b>: COVID-19 Stress Syndrome; COVID-19 Vaccine Adverse Reaction; COVID-19-Associated Thromboembolism; COVID-19 Post-Intensive Care Syndrome; COVID-19-Associated Stroke; COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Atorvastatin Calcium Tablets<br/><b>Sponsor</b>: Yang I. Pachankis<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>Understanding the Determinants of Mucosal Immunity and Optimizing the Diagnosis of Infection With SARS-CoV-2 Variants</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Blood sample collection; Other: Saliva sample collection; Other: Nasopharyngeal and nasal sample collection; Other: Exhaled Breath Condensate (EBC)<br/><b>Sponsors</b>: Institut Pasteur; Biogroup Laboratoire de biologie médicale<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 in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ALG-097558; Drug: Placebo; Drug: Midazolam; Drug: Itraconazole; Drug: Carbamazepine; Drug: ALG-097558 in solution formulation; Drug: ALG-097558 in tablet formulation<br/><b>Sponsor</b>: Aligos Therapeutics<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>Exercise for Health in Patients With Post-acute Sequelae of COVID-19</strong> - <b>Condition</b>: Long COVID<br/><b>Intervention</b>: Other: Rehabilitation program<br/><b>Sponsors</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona; Hospital de Mataró; University of Barcelona<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>Immunoadsorption Study Mainz in Adults With Post-COVID Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition<br/><b>Interventions</b>: Device: Immunoadsorption; Device: Sham-apheresis<br/><b>Sponsor</b>: University Medical Center Mainz<br/><b>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>SARS-CoV-2 Enters Human Leydig Cells and Affects Testosterone Production In Vitro</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a SARS-like coronavirus, continues to produce mounting infections and fatalities all over the world. Recent data point to SARS-CoV-2 viral infections in the human testis. As low testosterone levels are associated with SARS-CoV-2 viral infections in males and human Leydig cells are the main source of testosterone, we hypothesized that SARS-CoV-2 could infect human Leydig cells and impair their function. We successfully detected…</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>NLRP3 Inflammasome’s Activation in Acute and Chronic Brain Diseases-An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes</strong> - Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflammation players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent…</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>Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases</strong> - Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis 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>Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies</strong> - Human monoclonal antibodies (mAbs) that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been isolated from convalescent individuals and developed into therapeutics for SARS-CoV-2 infection. However, therapeutic mAbs for SARS-CoV-2 have been rendered obsolete by the emergence of mAb-resistant virus variants. Here we report the generation of a set of six human mAbs that bind the human angiotensin-converting enzyme-2 (hACE2) receptor, rather than 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>A peptide derived from HSP60 reduces proinflammatory cytokines and soluble mediators: a therapeutic approach to inflammation</strong> - Cytokines are secretion proteins that mediate and regulate immunity and inflammation. They are crucial in the progress of acute inflammatory diseases and autoimmunity. In fact, the inhibition of proinflammatory cytokines has been widely tested in the treatment of rheumatoid arthritis (RA). Some of these inhibitors have been used in the treatment of COVID-19 patients to improve survival rates. However, controlling the extent of inflammation with cytokine inhibitors is still a challenge because…</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>Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome</strong> - CONCLUSION: Current treatment guidelines for DRESS are based on case reports and expert opinion. Understanding the central role of eosinophils in DRESS pathogenicity emphasizes the need for future implementation of IL-5 axis blockade as steroid-sparing agents, potential therapy to steroid-resistant cases, and perhaps an alternative to CS treatment in certain DRESS patients more prone to CS toxicity.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dual domain recognition determines SARS-CoV-2 PLpro selectivity for human ISG15 and K48-linked di-ubiquitin</strong> - The Papain-like protease (PLpro) is a domain of a multi-functional, non-structural protein 3 of coronaviruses. PLpro cleaves viral polyproteins and posttranslational conjugates with poly-ubiquitin and protective ISG15, composed of two ubiquitin-like (UBL) domains. Across coronaviruses, PLpro showed divergent selectivity for recognition and cleavage of posttranslational conjugates despite sequence conservation. We show that SARS-CoV-2 PLpro binds human ISG15 and K48-linked di-ubiquitin…</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>TRIM21 promotes ubiquitination of SARS-CoV-2 nucleocapsid protein to regulate innate immunity</strong> - The innate immune response is the first line of host defense against viral infections, but its role in immunity against SARS-CoV-2 remains unclear. By using immunoprecipitation coupled with mass spectroscopy, we observed that the E3 ubiquitin ligase TRIM21 interacted with the SARS-CoV-2 nucleocapsid (N) protein and ubiquitinated it at Lys^(375) . Upon determining the topology of the TRIM21-mediated polyubiquitination chain on N protein, we then found that polyubiquitination led to tagging of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model</strong> - COVID-19, caused by SARS-CoV-2 infection, is currently among the most important public health concerns worldwide. Although several effective vaccines have been developed, there is an urgent clinical need for effective pharmaceutical treatments for treatment of COVID-19. Ivermectin, a chemical derivative of avermectin produced by Streptomyces avermitilis, is a macrocyclic lactone with antiparasitic activity. Recent studies have shown that ivermectin inhibits SARS-CoV-2 replication in vitro. In…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Efficacy and Mechanism Driven Study on the Impact of Hypoxia on Lipid Nanoparticle Mediated mRNA Delivery</strong> - Hypoxia is a common hallmark of human disease that is characterized by abnormally low oxygen levels in the body. While the effects of hypoxia on many small molecule-based drugs are known, its effects on several classes of next-generation medications including messenger RNA therapies warrant further study. Here, we provide an efficacy- and mechanism-driven study that details how hypoxia impacts the cellular response to mRNA therapies delivered using 4 different chemistries of lipid nanoparticles…</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>Aqueous cannabidiol β-cyclodextrin complexed polymeric micelle nasal spray to attenuate in vitro and ex-vivo SARS-CoV-2-induced cytokine storms</strong> - Cannabidiol (CBD) has a number of biological effects by acting on the cannabinoid receptors CB(1) and CB(2). CBD may be involved in anti-inflammatory processes via CB(1) and CB(2) receptors, resulting in a decrease of pro-inflammatory cytokines. However, CBD’s poor aqueous solubility is a major issue in pharmaceutical applications. The aim of the present study was to develop and evaluate a CBD nasal spray solution. A water-soluble CBD was prepared by complexation with β-cyclodextrin (β-CD) at 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>Bimekizumab efficacy and safety in patients with moderate to severe plaque psoriasis: two-year interim results from the open-label extension of the randomized BE RADIANT phase 3b trial</strong> - CONCLUSIONS: High PASI100 responses achieved with bimekizumab over 48 weeks were sustained through Week 96; secukinumab patients who switched to bimekizumab achieved similar response by Week 96.</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>Detection of SARS-CoV-2 Antibodies in Immunoglobulin Products</strong> - CONCLUSION: Overall, more recent Ig products (expiration dates: 2023 - 2025) contained significantly higher binding and inhibition activities against SARS-CoV-2 proteins, as compared to earlier, or pre-pandemic products. Normal donor SARS-CoV-2 antibodies are capable of inhibiting ACE2-binding activities and may provide a therapeutic benefit for patients who do not make a robust vaccine response.</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>Small molecule inhibitor CRT0066101 inhibits cytokine storm syndrome in a mouse model of lung injury</strong> - Pneumonia is an acute inflammation of the lungs induced by pathogenic microorganisms, immune damage, physical and chemical factors, and other factors, and the latest outbreak of novel coronavirus pneumonia is also an acute lung injury (ALI) induced by viral infection. However, there are currently no effective treatments for inflammatory cytokine storms in patients with ALI/acute respiratory distress syndrome (ARDS). Protein kinase D (PKD) is a highly active kinase that has been shown to be…</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>Impact of the Recognition Part of Dipeptidyl Nitroalkene Compounds on the Inhibition Mechanism of Cysteine Proteases Cruzain and Cathepsin L</strong> - Cysteine proteases (CPs) are an important class of enzymes, many of which are responsible for several human diseases. For instance, cruzain of protozoan parasite Trypanosoma cruzi is responsible for the Chagas disease, while the role of human cathepsin L is associated with some cancers or is a potential target for the treatment of COVID-19. However, despite paramount work carried out during the past years, the compounds that have been proposed so far show limited inhibitory action against these…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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