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178 lines
47 KiB
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<title>19 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2</strong> -
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Proline is widely known as the only proteogenic amino acid with a secondary amine. In addition to its crucial role in protein structure, the secondary amino acid modulates neurotransmission and regulates the kinetics of signaling proteins. To understand the structural basis of proline import, we solved the structure of the proline transporter SIT1 in complex with the COVID-19 viral receptor ACE2 by cryo-electron microscopy. The structure of pipecolate-bound SIT1 reveals the specific sequence requirements for proline transport in the SLC6 family and how this protein excludes amino acids with extended side chains. By comparing apo and substrate-bound SIT1 states, we also identify the structural changes which link substrate release and opening of the cytoplasmic gate, and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.17.541173v1" target="_blank">Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2</a>
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<li><strong>Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders</strong> -
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Red blood cell (RBC) disorders affect billions worldwide. While alterations in the physical properties of aberrant RBCs and associated hemodynamic changes are readily observed, in conditions such as sickle cell disease and iron deficiency, RBC disorders can also be associated with vascular dysfunction. The mechanisms of vasculopathy in those diseases remain unclear and scant research has explored whether biophysical alterations of RBCs can directly affect vascular function. Here we hypothesize that the purely physical interactions between aberrant RBCs and endothelial cells, due to the margination of stiff aberrant RBCs, play a key role in this phenomenon for a range of disorders. This hypothesis is tested by direct simulations of a cellular scale computational model of blood flow in sickle cell disease, iron deficiency anemia, COVID-19, and spherocytosis. We characterize cell distributions for normal and aberrant RBC mixtures in straight and curved tubes, the latter to address issues of geometric complexity that arise in the microcirculation. In all cases aberrant RBCs strongly localize near the vessel walls (margination) due to contrasts in cell size, shape, and deformability from the normal cells. In the curved channel, the distribution of marginated cells is very heterogeneous, indicating a key role for vascular geometry. Finally, we characterize the shear stresses on the vessel walls; consistent with our hypothesis, the marginated aberrant cells generate large transient stress fluctuations due to the high velocity gradients induced by their near-wall motions. The anomalous stress fluctuations experienced by endothelial cells may be responsible for the observed vascular inflammation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541016v1" target="_blank">Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders</a>
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</div></li>
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<li><strong>CParty: Conditional partition function for density-2RNA pseudoknots</strong> -
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RNA molecules fold into biologically important functional structures. Efficient dynamic programming RNA (secondary) structure prediction algorithms restrict the the search space to evade NP-hardness of general pseudoknot prediction. While such prediction algorithms can be extended to provide a stochastic view on RNA ensembles, they are either limited to pseudoknot-free structures or extremely complex. To overcome this dilemma, we follow the hierarchical folding hypothesis, i.e. the bio-physically well-motivated assumption that non-crossing structures fold relatively fast prior to the formation of pseudoknot interactions. Thus, we efficiently compute the conditional partition function (CPF) given a non-crossing structure G for a subset of pseudoknotted stuctures i.e. density-2 structures G {cup} G' for non-crossing disjoint G'. Notably, this enables sampling from the hierarchical distribution P (G'|G). As our main contribution, we devise the algorithm CParty, which transfers the dynamic programming scheme of HFold to a partition function variant by for the first time de-ambiguating its decomposition of density-2 structures. Compared to the only other available pseudoknot partition function algorithm, which covers simple pseudoknots, our method covers a much larger structure class; at the same time, it is significantly more efficient (reducing the time as well as the space complexity by a quadratic factor). Summarizing, we provide a highly efficient (cubic time) algorithm for the stochastic analysis of pseudoknotted RNAs, which enables novel applications. For example, we discuss how the CPF for a pseudoknotted therapeutic target in SARS-CoV-2 provides insights into RNA structure formation kinetic paths.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541023v1" target="_blank">CParty: Conditional partition function for density-2RNA pseudoknots</a>
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<li><strong>Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China</strong> -
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Abstract Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL) and disability in 1082 severely and critically patients with COVID-19 between December 8, 2022 and February 9, 2023 in Shanghai, China. The final 60-day follow-up was completed on April 10, 2023. Results: Among 1082 patients (mean age, 78.0 years), 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24-0.79]) and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, Baricitinib, and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]), and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Paxlovid, Azvudine and therapeutic anticoagulation showed significant reduction in disability (p<0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in resource-limited scenario. Treatment with IL-6 receptor antagonist, Baricitinib, and a-thymosin also had high probabilities of benefit of improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine and therapeutic anticoagulation could significantly reduce disability at day 60. Keyword: COVID-19; Azvudine; Paxlovid; Interleukin-6 receptor antagonist; Baricitinib, α-thymosin, Intravenous immunoglobulin
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289325v3" target="_blank">Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China</a>
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<li><strong>Delineating a ‘15-Minute City’: An Agent-based Modeling Approach to Estimate the Size of Local Communities</strong> -
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With progressively increased people living in cities, and lately the global COVID-19 outbreak, human mobility within cities has changed. Coinciding with this change, is the recent uptake of the ‘15-Minute City’ idea in urban planning around the world. One of the hallmarks of this idea is to create a high quality of life within a city via an acceptable travel distance (i.e., 15 minutes). However, a definitive benchmark for defining a ‘15-Minute City’ has yet to be agreed upon due to the heterogeneous character of urban morphologies worldwide. To shed light on this issue, we develop an agent-based model named ‘D-FMCities’ utilizing realistic street networks and points-of-interest, in this instance the borough of Queens in New York City as a test case. Through our modeling we grow diverse communities from the bottom up and estimate the size of such local communities to delineate 15-minute cities. Our findings suggest that the model could be helpful to detect the flexibility of defining the extent of a ‘15-minute city’ and consequently support uncovering the underlying factors that may affect its various definitions and diverse sizes throughout the world.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/p7fdz/" target="_blank">Delineating a ‘15-Minute City’: An Agent-based Modeling Approach to Estimate the Size of Local Communities</a>
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<li><strong>Promoting Urban Farming for Creating Sustainable Cities in Nepal</strong> -
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This paper responds to the research question, “can urban farming in Nepal help create sustainable cities?” Especially after the COVID-19 pandemic, urban residents have begun to realize that food transported from long distances is not always reliable. Urban farming can help produce fresh food locally and help urban residents become self-reliant by engaging in healthy eating habits and practicing sustainable agricultural techniques in food-desert areas, while creating a positive impact on the environment through regenerative agricultural methods. In doing so, urban farms can help the growers save on food expenditures and even earn some additional income, while also improving air quality and minimizing the effects of urban heat islands. This practice also helps reduce greenhouse gases through plant carbon use efficiency (CUE), as vegetation carbon dynamics (VCD) can be adjusted while supporting the circular economy. As urban lands command higher prices than agricultural land, urban farming usually happens on residential yards, roofs, balconies, community gardens, and dedicated areas in public parks. Rainwater harvesting and redirecting can help irrigate urban farms, which can be part of rain gardens. The national census of 2021 identified that 66% of Nepal’s population lives in urban areas. However, the World Bank (2018) showed that only 21 of Nepal’s population was projected to live in urban areas in 2021. It is not debatable that the urbanization process in Nepal is on the rise. Thus, urban agriculture can play an important role in supplementing residents’ food needs. Many cities in Nepal have already successfully adapted to urban farming wherein residents grow food on their building sites, balconies, and rooftop, often growing plants in pots, vases, and other types of containers. The UN-Habitat, with the support of the European Union and local agencies, published a rooftop farming training manual (2014), showing the feasibility of urban farming in Nepal. This paper discusses how public-private partnership (PPP) can promote urban agriculture and make the process more effective and attractive to urban-farming households. It also analyzes how a PPP approach also facilitates the use of better technology, advisory support, and use of research extension activities. This paper draws on a literature review, uses remote-sensing imagery data and data from National Census Nepal 2021, and the authors’ professional experiences related to best practices in the areas to analyze the benefits and challenges related to urban farming both in Nepal and Arizona, USA. The paper provides recommendations for Nepali cities to maximize the benefit provided by urban farming.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/xz4t7/" target="_blank">Promoting Urban Farming for Creating Sustainable Cities in Nepal</a>
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<li><strong>Minority Communities United Against COVID-19: It Takes a Village</strong> -
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COVID-19 has illuminated how racial inequities across multiple institutions in the United States have converged and resulted in profound and lasting negative impacts on people and communities of color. Disparities in the treatment of Native (Indigenous) Americans, African (Black) Americans, and Latinx individuals in the United States concomitant with health disparities more prevalent in these populations have resulted in COVID-19 death rates that have been consistently higher than that of white counterparts and at rates that are significantly higher than their percentage of the population. While reports have focused have necessarily focused on the despair in these communities and the disparities in case and death rates, we report on the historical resilience of these communities and how this has been used to mobilize interventions in these communities that have served to mitigate the negative impact of COVID-19.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/3zm7w/" target="_blank">Minority Communities United Against COVID-19: It Takes a Village</a>
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<li><strong>Longitudinal analysis of memory T follicular helper cells and antibody response following CoronaVac vaccination</strong> -
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The inactivated vaccine CoronaVac is one of the most widely used COVID-19 vaccines globally. However, the longitudinal evolution of the immune response induced by CoronaVac remains elusive compared to other vaccine platforms. Here, we recruited 88 healthy individuals that received 3 doses of CoronaVac vaccine. We longitudinally evaluated their polyclonal and antigen-specific CD4+ T cells and neutralizing antibody response after receiving each dose of vaccine for over 300 days. Both the 2nd and 3rd dose of vaccination induced robust spike-specific neutralizing antibodies, with a 3rd vaccine further increased the overall magnitude of antibody response, and neutralization against Omicron sub-lineages B.1.1.529, BA.2, BA.4/BA.5 and BA.2.75.2. Spike-specific CD4+ T cell and circulating T follicular helper (cTFH) cells were markedly increased by the 2nd and 3rd dose of CoronaVac vaccine, accompanied with altered composition of functional cTFH cell subsets with distinct effector and memory potential. Additionally, cTFH cells are positively correlated with neutralizing antibody titers. Our results suggest that CoronaVac vaccine-induced spike-specific T cells are capable of supporting humoral immunity for long-term immune protection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541033v1" target="_blank">Longitudinal analysis of memory T follicular helper cells and antibody response following CoronaVac vaccination</a>
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<li><strong>SARS-CoV-2 infection leads to Tau pathological signature in neurons</strong> -
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Background: The coronavirus disease 19 (COVID-19) has represented an issue for global health since its outbreak in March 2020. It is now evident that the SARS-CoV-2 infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimer's disease. Little is known about the molecular basis of these manifestations. Methods: Several SARS-CoV-2 strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated using immunoblot and immunofluorescence on cellular extracts, subcellular fractions, and brain tissue. The viral proteins Spike, Nucleocapsid, and Membrane were overexpressed in SH-SY5Y cells and the direct effect on Tau phosphorylation was checked using immunoblot experiments. Results: Upon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimer's disease and other tauopathies. Moreover, this event increases Tau's propensity to form insoluble aggregates and alters its subcellular localization. Conclusions: Our data support the evidence that SARS-CoV-2 infection in the Central Nervous System triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.17.541098v1" target="_blank">SARS-CoV-2 infection leads to Tau pathological signature in neurons</a>
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<li><strong>Tracing the origin of SARS-CoV-2 Omicron-like Spike sequences detected in wastewater</strong> -
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Background: The origin of divergent SARS-CoV-2 spike sequences found in wastewater, but not in clinical surveillance, remains unclear. These cryptic wastewater sequences have harbored many of the same mutations that later emerged in Omicron lineages. We first detected a cryptic lineage in municipal wastewater in Wisconsin in January 2022. Named the Wisconsin Lineage, we sought to determine the geographic origin of this virus and characterize its persistence and evolution over time. Methods: We systematically sampled maintenance holes to trace the origin of the Wisconsin Lineage. We sequenced spike RBD domains, and where possible, whole viral genomes, to characterize the evolution of this lineage over the 13 consecutive months that it was detectable. Findings: The persistence of the Wisconsin Lineage signal allowed us to trace it from a central wastewater plant to a single facility, with a high concentration of viral RNA. The viral sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in Wisconsin at low levels from October 2020 to February 2021, while mutations in the spike gene resembled those subsequently found in Omicron variants. Interpretation: We propose that prolonged detection of the Wisconsin Lineage in wastewater represents persistent shedding of SARS-CoV-2 from an infected individual, with ongoing within-host viral evolution leading to an ancestral B.1.234 virus accumulating Omicron-like mutations. Funding: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention (CDC), National Institute on Drug Abuse (NIDA), and the Center for Research on Influenza Pathogenesis and Transmission.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.28.22281553v2" target="_blank">Tracing the origin of SARS-CoV-2 Omicron-like Spike sequences detected in wastewater</a>
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<li><strong>Detection of SARS-CoV-2 B.1.1.529 (Omicron) variant by SYBR Green‑based RT‑qPCR</strong> -
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Background: The COVID-19 pandemic is unceasingly spreading across the globe, and recently a highly transmissible Omicron SARS-CoV-2 variant (B.1.1.529) has been discovered in South Africa and Botswana. Rapid identification of this variant is essential for pandemic assessment and containment. However, variant identification is mainly being performed using expensive and time-consuming genomic sequencing. Methods and results: In this study we propose an alternative RT-qPCR approach for the detection of the Omicron BA.1 variant using a low-cost and rapid SYBR Green method. We have designed specific primers to confirm the deletion mutations in the spike (S ∆143-145) and the nucleocapsid (N ∆31-33) which are characteristics of this variant. For the evaluation, we used 120 clinical samples from patients with PCR-confirmed SARS-CoV-2 infections, and displaying an S-gene target failure (SGTF) when using TaqPath COVID-19 kit (Thermo Fisher Scientific, Waltham, USA) that included the ORF1ab, S, and N gene targets. Our results showed that all the 120 samples harbored S ∆143-145 and N ∆31-33, which was further confirmed by Whole genome sequencing (WGS) of 4 samples thereby validating our SYBR Green-based protocol. Conclusions: This protocol can be easily implemented to rapidly confirm the diagnosis of the Omicron BA.1 variant in COVID-19 patients and prevent its spread among populations, especially in countries with high prevalence of SGTF profile.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.16.23289717v1" target="_blank">Detection of SARS-CoV-2 B.1.1.529 (Omicron) variant by SYBR Green‑based RT‑qPCR</a>
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<li><strong>Examining outpatients’ hand hygiene behaviour and its relation to other infection prevention measures.</strong> -
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Background: The increasing demand for outpatient care is associated with a higher risk of infection transmission in these settings. However, there is limited research on infection prevention and control practices in ambulatory clinics, and none focuses on patients. Aim: Consequently, this study aims to examine outpatients’ hand hygiene behaviours, their determinants, and their associations with other infection prevention measures during the COVID-19 pandemic. Methods: We observed the hand hygiene behaviour of patients in one outpatient clinic and surveyed outpatients in five clinics about their hand hygiene practice in outpatient facilities. A questionnaire based on the Theoretical Domains Framework (TDF) was used to examine predictors of the behaviour. Moreover, patients indicated their compliance with COVID-19 infection prevention measures, vaccination status, disease risk perception, and vaccine hesitancy. Findings: Observed hand hygiene rates among 618 patients were low (12.8%), while 67.3% of the 300 surveyed patients indicated sanitising their hands upon entering the clinic. The TDF domains memory, attention, and decision processes, and emotions significantly predicted both current (today’s) and general hand hygiene behaviour in outpatient clinics. Hand hygiene behaviour and compliance with COVID-19 infection prevention showed a positive association; however, no significant connection was found with patients’ vaccination status, suggesting different behavioural motivators. Conclusion: Hand hygiene among outpatients should be improved through interventions focusing on helping patients remember to clean their hands. More research on infection prevention in outpatient facilities is needed to ensure patient safety.
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🖺 Full Text HTML: <a href="https://osf.io/wrzfa/" target="_blank">Examining outpatients’ hand hygiene behaviour and its relation to other infection prevention measures.</a>
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<li><strong>Single-cycle SARS-CoV-2 vaccine elicits high protection and sterilizing immunity in hamsters</strong> -
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Vaccines have been central in ending the COVID-19 pandemic, but newly emerging SARS-CoV-2 variants increasingly escape first-generation vaccine protection. To fill this gap, live particle-based vaccines mimicking natural infection aim at protecting against a broader spectrum of virus variants. We designed "single-cycle SARS-CoV-2 viruses" (SCVs) that lack essential viral genes, possess superior immune-modulatory features and provide an excellent safety profile in the Syrian hamster model. Full protection of all intranasally vaccinated animals was achieved against an autologous challenge with SARS-CoV-2 virus using an Envelope-gene-deleted vaccine candidate. By deleting key immune-downregulating genes, sterilizing immunity was achieved with an advanced candidate without virus spread to contact animals. Hence, SCVs have the potential to induce a broad and durable protection against COVID-19 superior to a natural infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.17.541127v1" target="_blank">Single-cycle SARS-CoV-2 vaccine elicits high protection and sterilizing immunity in hamsters</a>
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<li><strong>Discovery of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro)</strong> -
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Papain-like protease (PLpro) is a viral protease found in some coronaviruses, including SARS-CoV-2, the virus that causes COVID -19, and is a target for antiviral drug development. Inhibition of PLpro activity could potentially limit viral replication, making it an attractive target for antiviral drug development. This work describes the discovery of novel allosteric residues of SARS-CoV-2 PLpro that can be targeted with antiviral drugs. First, a computational analysis was performed to identify potential druggable pockets on the surface of SARS-CoV-2 PLpro. The computational analysis predicted three druggable pockets that span the surface of PLpro and are located at the interface of its four domains. Pocket 1 is located at the interface between the Ub1 and thumb domains, pocket 2 is at the interface between the thumb, finger, and palm domains, and pocket 3 is at the interface between the finger and palm domains. Targeted alanine mutagenesis of selected residues with important structural interactions revealed that 12 of 23 allosteric residues (D12, Y71, Y83, Q122, Q133, R140, T277, S278, S212, Y213, K254, and Y305) are essential for maintaining a catalytically active and thermodynamically stable PLpro. This work provides experimental confirmation of essential contacts in the allosteric sites of PLpro that could be targeted with non-competitive inhibitors as novel therapeutics against COVID -19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.540953v1" target="_blank">Discovery of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro)</a>
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<li><strong>Defining distinct RNA-protein interactomes of SARS-CoV-2 genomic and subgenomic RNAs</strong> -
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Host RNA binding proteins recognize viral RNA and play key roles in virus replication and antiviral defense mechanisms. SARS-CoV-2 generates a series of tiered subgenomic RNAs (sgRNAs), each encoding distinct viral protein(s) that regulate different aspects of viral replication. Here, for the first time, we demonstrate the successful isolation of SARS-CoV-2 genomic RNA and three distinct sgRNAs (N, S, and ORF8) from a single population of infected cells and characterize their protein interactomes. Over 500 protein interactors (including 260 previously unknown) were identified as associated with one or more target RNA at either of two time points. These included protein interactors unique to a single RNA pool and others present in multiple pools, highlighting our ability to discriminate between distinct viral RNA interactomes despite high sequence similarity. The interactomes indicated viral associations with cell response pathways including regulation of cytoplasmic ribonucleoprotein granules and posttranscriptional gene silencing. We validated the significance of five protein interactors predicted to exhibit antiviral activity (APOBEC3F, TRIM71, PPP1CC, LIN28B, and MSI2) using siRNA knockdowns, with each knockdown yielding increases in viral production. This study describes new technology for studying SARS-CoV-2 and reveals a wealth of new viral RNA-associated host factors of potential functional significance to infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.15.540806v1" target="_blank">Defining distinct RNA-protein interactomes of SARS-CoV-2 genomic and subgenomic RNAs</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>Investigation of the Effect on Cognitive Skills of COVID-19 Survivors</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: green walking and intelligence gam<br/><b>Sponsors</b>: Bayburt University; Karadeniz Technical 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>Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19</strong> - <b>Condition</b>: Patients With COVID-19<br/><b>Interventions</b>: Drug: The drug “Rutan 0.1”.; Other: Basic treatment<br/><b>Sponsor</b>: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>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>Studying the Efficiency of the Natural Preparation Rutan in Children in the Treatment of COVID-19, ARVI</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Interventions</b>: Drug: Rutan 25 mg; Other: Control group<br/><b>Sponsor</b>: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>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>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>Use of a Hypochlorous Acid Spray Solution in the Treatment of COVID-19 Patients : COVICONTROL Study .</strong> - <b>Condition</b>: SARS CoV 2 Infection<br/><b>Interventions</b>: Other: Spray with Hypochlorous Acid Group; Other: Spray with Placebo Group<br/><b>Sponsor</b>: University of Monastir<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>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>Telerehabilitation Program and Detraining in Patients With Post-COVID-19 Sequelae</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program<br/><b>Sponsor</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona<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 Vaccine Uptake Amongst Underserved Populations in East London</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccination Refusal<br/><b>Intervention</b>: Device: Patient Engagement tool<br/><b>Sponsors</b>: Queen Mary University of London; Social Action for Health<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>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>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>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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</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>Optimization of urban emergency support material distribution under major public health emergencies based on improved sparrow search algorithm</strong> - The outbreak of major public health emergencies such as the coronavirus epidemic has put forward new requirements for urban emergency management procedures. Accuracy and effective distribution model of emergency support materials, as an effective tool to inhibit the deterioration of the public health sector, have gradually become a research hotspot. The distribution of urban emergency support devices, under the secondary supply chain structure of “material transfer center-demand point,” which…</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>Passive swab versus grab sampling for detection of SARS-CoV-2 markers in wastewater</strong> - Early detection of the COVID-19 virus, SARS-CoV-2, is key to mitigating the spread of new outbreaks. Data from individual testing is increasingly difficult to obtain as people conduct non-reported home tests, defer tests due to logistics or attitudes, or ignore testing altogether. Wastewater based epidemiology is an alternative method for surveilling a community while maintaining individual anonymity; however, a problem is that SARS-CoV-2 markers in wastewater varies throughout the day….</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>Oxalic acid blocked the binding of spike protein from SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variants to human angiotensin-converting enzymes 2</strong> - An epidemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Moreover, the emergence of SARS-CoV-2 variants of concern, such as Delta and Omicron, has seriously challenged the application of current therapeutics including vaccination and drugs. Relying on interaction of spike protein with receptor angiotensin-converting enzymes 2 (ACE2), SARS-CoV-2 successfully invades to the host cells, which indicates 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>Antifungal Activity and Potential Action Mechanism of Allicin against Trichosporon asahii</strong> - Trichosporon asahii is an emerging opportunistic pathogen that causes potentially fatal disseminated trichosporonosis. The global prevalence of coronavirus disease 2019 (COVID-19) poses an increasing fungal infection burden caused by T. asahii. Allicin is the main biologically active component with broad-spectrum antimicrobial activity in garlic. In this study, we performed an in-depth analysis of the antifungal characteristics of allicin against T. asahii based on physiological, cytological,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Nucleocapsid Protein Is a Potential Therapeutic Target for Anticoronavirus Drug Discovery</strong> - SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, is a highly contagious positive-sense RNA virus. Its explosive community spread and the emergence of new mutant strains have created palpable anxiety even in vaccinated people. The lack of effective anticoronavirus therapeutics continues to be a major global health concern, especially due to the high evolution rate of SARS-CoV-2. The nucleocapsid protein (N protein) of SARS-CoV-2 is highly conserved and involved in diverse processes 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>Six-month immune responses to mRNA-1273 Vaccine in cART-treated late presenter people living with HIV according to previous SARS-CoV-2 Infection</strong> - CONCLUSIONS: Altogether, these findings support the need for additional vaccine doses in PLWH with a history of advanced immune depression and poor immune recovery on effective cART.</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><em>In silico</em> design of miniprotein to inhibit SARS-CoV-2 variant Omicron spike protein</strong> - Omicron is a novel variant of SARS-CoV-2 that is currently spreading globally as the dominant strain. The virus first enters the host cell through the receptor binding domain (RBD) of the spike protein by interacting with the angiotensin-converting enzyme 2 (ACE2). Thus, the RBD protein is an ideal target for the design of drugs against the Omicron variant. Here, we designed several miniprotein inhibitors in silico to combat the SARS-CoV-2 Omicron variant using single- and double-point mutation…</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>Conformal Hydrogel-Skin Coating on a Microfluidic Channel through Microstamping Transfer of the Masking Layer</strong> - Poly(dimethylsiloxane) (PDMS) is used in microfluidics owing to its biocompatibility and simple fabrication. However, its intrinsic hydrophobicity and biofouling inhibit its microfluidic applications. Conformal hydrogel-skin coating for PDMS microchannels, involving the microstamping transfer of the masking layer, is reported herein. A selective uniform hydrogel layer with a thickness of ∼1 μm was coated in diverse PDMS microchannels with a resolution of ∼3 μm, maintaining its structure 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>The C-terminal 32-mer fragment of hemoglobin alpha is an amyloidogenic peptide with antimicrobial properties</strong> - Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has…</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>Challenges and Progress in Designing Broad-Spectrum Vaccines Against Rapidly Mutating Viruses</strong> - Viruses evolve to evade prior immunity, causing significant disease burden. Vaccine effectiveness deteriorates as pathogens mutate, requiring redesign. This is a problem that has grown worse due to population increase, global travel, and farming practices. Thus, there is significant interest in developing broad-spectrum vaccines that mitigate disease severity and ideally inhibit disease transmission without requiring frequent updates. Even in cases where vaccines against rapidly mutating…</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>Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies</strong> - CONCLUSION: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of dual S-RBD/NRP1-targeting peptides: structure-based virtual screening, synthesis, biological evaluation, and molecular dynamics simulation studies</strong> - Both receptor-binding domain in spike protein (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human neuropilin-1 (NRP1) are important in the virus entry, and their concomitant inhibition may become a potential strategy against the SARS-CoV-2 infection. Herein, five novel dual S-RBD/NRP1-targeting peptides with nanomolar binding affinities were identified by structure-based virtual screening. Particularly, RN-4 was found to be the most promising peptide targeting S-RBD…</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>Compounds from myrtle flowers as antibacterial agents and SARS-CoV-2 inhibitors: <em>In-vitro</em> and molecular docking studies</strong> - Plants and their related phytochemicals play a key role in the treatment of bacterial and viral infections, which inspire scientists to design and develop more efficient drugs starting from the phytochemical active scaffold. This work aims to characterize the chemical compounds of Myrtus communis essential oil (EO) from Algeria and to evaluate its in vitro antibacterial effect, as well as the in silico anti-SARS-CoV-2 activity. The chemical profile of hydrodistilled EO from myrtle flowers was…</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>Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines</strong> - CONCLUSION: KTRs’ humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.</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>Interactive network pharmacology and electrochemical analysis reveals electron transport-mediating characteristics of Chinese medicine formula Jing Guan Fang</strong> - BACKGROUND: Jing Guan Fang (JGF) is an anti-COVID-19 Chinese Medicine decoction comprised of five medicinal herbs to possess anti-inflammatory and antiviral properties for treatment. This study aims to electrochemically decipher the anti-coronavirus activity of JGF and show that microbial fuel cells may serve as a platform for screening efficacious herbal medicines and providing scientific bases for the mechanism of action (MOA) of TCMs.</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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