- The Situation During the COVID-19 Pandemic: A Snapshot in Germany -
During government-implemented restrictions in the wake of the COVID-19 pandemic, people’s everyday lives changed profoundly. However, there is to date little research chronicling how people perceived their changed everyday lives and which consequences this had. In a two-wave study, we examined the psychological characteristics of people’s situations and their correlates during shutdown in a large German sample (NT1 = 1,353; NT2 = 446). First, we compared characteristics during government-issued restrictions with retrospective accounts from before and with a follow-up assessment 6 to 7 months later when many restrictions had been lifted. We found that mean levels were lower and variances were higher for most characteristics during the shutdown. Second, the experience of certain situation characteristics was associated in meaningful and theoretically expected ways with people’s traits, appraisals of the COVID-19 crisis, and subjective well-being. Lastly, situation characteristics often substantially explained the associations of traits with appraisals and well-being. Our findings highlight the importance of considering perceived situations as these contribute to people’s functioning during crises.
- Who is impacted? Personality predicts individual differences in psychological consequences of the COVID-19 pandemic in Germany -
The COVID-19 pandemic has led to changes in people’s private and public lives that are unprecedented in modern history. However, little is known about the differential psychological consequences of restrictions that have been imposed to fight the pandemic. In a large and diverse German sample (N = 1,320), we examined how individual differences in psychological consequences of the pandemic (perceived restrictiveness of government-supported measures; global pandemic-related appraisals; subjective well-being) were associated with a broad set of faceted personality traits (Big Five, Honesty-Humility, Dark Triad). Facets of Extraversion, Neuroticism, and Openness were among the strongest and most important predictors of psychological outcomes, even after controlling for basic socio-demographic variables (gender, age). These findings suggest that psychological consequences of the pandemic depend on personality and thus add to the growing literature on the importance of considering individual differences in crisis situations.
- Isogenic iPSC-derived proximal and distal lung-on-chip models: Tissue- and virus-specific immune responses in human lungs -
Micro-physiological systems (MPS) are set to play a vital role in preclinical studies, particularly in the context of future viral pandemics. Nonetheless, the development of MPS is often impeded by the scarcity of reliable cell sources, especially when seeking various organs or tissues from a single patient for comparative analysis of the host immune response. Herein, we developed human airway-on-chip and alveolus-on-chip models using induced pluripotent stem cell (iPSC)-derived isogenic lung progenitor cells. Both models demonstrated the replication of two different respiratory viruses, namely SARS-CoV-2 and Influenza, as well as related cellular damage and innate immune responses-on-chip. Our findings reveal distinct immune responses to SARS-CoV-2 in the proximal and distal lung-on-chip models. The airway chips exhibited a robust interferon (IFN)-dependent immune response, whereas the alveolus chips exhibited dysregulated IFN activation but a significantly upregulated chemokine pathway. In contrast, Influenza virus infection induced a more pronounced immune response and cellular damage in both chip models compared to SARS-CoV-2. Thus, iPSC-derived lung-on-chip models may aid in quickly gaining insights into viral pathology and screening potential drugs for future pandemics.
- REPORT : Study on ‘Institutionalizing Science Advice to Governments -
The provision of appropriate science advice to governments is of national, regional, and global importance. However, many countries, especially in the developing world, lack effective framework to provide science advice to governments, which was laid bare during the COVID-19 pandemic. Hence, there is an urgent need to describe and analyse the structures and processes providing science advice to governments with a view to strengthening science advice. Science advice requires synthesizing and brokering valid, relevant, and reliable scientific evidence in respect of different policies. The National Academy of Sciences of Sri Lanka conducted a study on the status and processes of institutionalizing Science Advice to Governments in the Australasian region. The aims of the study were to a) propose and facilitate the development and strengthening of systematic science advice in member countries and its institutionalization b) Improve awareness among partners on a range of laws and regulations that exist legitimizing institutions and the processes used for government science advice c) develop capacities of participating academies in providing science advice d) enable academies to play a role and be part of the science advice process The methodology included administration of a structured questionnaire to gather data for the Situation Analysis with respect to science advice in partner countries. The questionnaire responses were categorized under several headings identified as the ‘Colombo Framework’: Selection of advisors, organizational structures to provide advice, the process followed to collate and synthesize advice, the process of communication, and evaluation of the process and impact of advice. The results showed a diversity of responses indicating a range of structures and processes: • The structures and types of advisors included, chief science advisor or advisors, a science advisory office or agency, science advisory boards, science advisory councils and ad-hoc arrangements during emergencies or crises, such as task forces. • Selection of advisors varied from appointments by an executive authority to nominations by science organizations or selection processes based on academic credentials. • The initial framing of questions requiring science advice were by policymakers, parliament committee or the President and advisory council. • Collation and synthesizing evidence: The methods used included systematic reviews, meta-analyses, through surveys, consultative meetings, expert opinion, foresight tools and workshops and/meetings of the experts where the evidence was reviewed. • The process of communicating science advice included reports issued by the science advisors, or advice directed to the Presidential Office, to Cabinet office, or submitted through Secretary of the Ministry of Science and Technology to the Head of State, or reports to the relevant minister and presidential secretariat. • The impact of science advice on policy was rarely evaluated. • Case Studies for individual countries supplemented the situation analysis for that country. • A SWOT analyses was compiled based on each country responses to reflect the totality of responses and for guidance in drafting a framework for Roadmaps for each country. As part of the project a three-day workshop was held in Colombo, Sri Lanka on ‘Institutionalizing Science Advice to Governments’ 6-8 July 2023. A descriptive ‘Colombo Declaration’ was released calling on governments to partner with scientists and demonstrate stronger commitment in strengthening action to institutionalize science advice to governments. The concluding session described future actions of developing Roadmaps and Case Studies by each partner country. The contextualized roadmaps will be developed through an iterative process and ‘work in progress’ submitted by most partner agencies were included in the report. The key outcomes of the Project were the following: 1. Documentation of Science Advice Systems in countries with situation analysis, reinforced with case studies and SWOT analyses and a framework for contextualized roadmaps that could form the foundation for further activities with support from the IAP and AASSA. 2. Developed and disseminated the ‘Colombo Declaration’ calling on governments to institutionalize science advice 3. Availability of validated questionnaire and framework (‘Colombo framework’) to replicate similar studies elsewhere. 4. Development of a process for promotion of institutionalization of science advice to governments that could be replicated in other countries or regions. 5. Promoted awareness among public, public administrators and policymakers and younger generation of scientists to be part of this transformative process, particularly to ensure continuity of efforts. 6. Contextualized Roadmaps design process has been initiated that is meant to trigger further discussions.
- DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets. Report on Serbia -
The aim of this country report is to provide answers to the following DEFEN-CE research questions: 1. What public policy and social dialogue measures targeting the selected vulnerable groups were implemented to employment and social protection during the COVID-19 pandemic 2020-2022? 2. To what extent and how did social dialogue play a role in the implementation of social and employment rights of selected vulnerable groups in the COVID-19 pandemic between 2020 and 2022? 3. What lessons and opportunities does the COVID-19 pandemic yield for strengthening social dialogue in the studied countries? In order to answer these questions we used a mixed-method approach, combining qualitative and quantitative techniques. We started with the collection of the most relevant labour market data, especially regarding vulnerable groups. Then, by using the desk research we were able to synthesize the existing knowledge on public policies and social dialogue in the COVID-19 crisis. Finally, we conducted 10 semi-structured interviews to explore in-depth the role of social partners in the defence of the vulnerable groups.
- Gaining Biological Insights through Supervised Data Visualization -
Dimensionality reduction-based data visualization is pivotal in comprehending complex biological data. The most common methods, such as PHATE, t-SNE, and UMAP, are unsupervised and therefore reflect the dominant structure in the data, which may be independent of expert-provided labels. Here we introduce a supervised data visualization method called RF-PHATE, which integrates expert knowledge for further exploration of the data. RF-PHATE leverages random forests to capture intricate feature-label relationships. Extracting information from the forest, RF-PHATE generates low-dimensional visualizations that highlight relevant data relationships while disregarding extraneous features. This approach scales to large datasets and applies to classification and regression. We illustrate RF-PHATE's prowess through three case studies. In a multiple sclerosis study using longitudinal clinical and imaging data, RF-PHATE unveils a sub-group of patients with non-benign relapsing-remitting Multiple Sclerosis, demonstrating its aptitude for time-series data. In the context of Raman spectral data, RF-PHATE effectively showcases the impact of antioxidants on diesel exhaust-exposed lung cells, highlighting its proficiency in noisy environments. Furthermore, RF-PHATE aligns established geometric structures with COVID-19 patient outcomes, enriching interpretability in a hierarchical manner.
- scSniper: Single-cell Deep Neural Network-based Identification of Prominent Biomarkers -
Discovering disease biomarkers at the single-cell level is crucial for advancing our understanding of diseases and improving diagnostic accuracy. However, current computational methods often have limitations, such as a reliance on prior knowledge, constraints to unimodal data, and the use of conventional statistical tests for feature selection. To address these issues, we introduce scSniper, a novel approach that employs a specialized deep neural network framework tailored for robust single-cell multi-omic biomarker detection. A standout feature of scSniper is the mimetic attention block, enhancing alignment across multi-modal data types. Moreover, scSniper utilizes sensitivity analysis based on a deep neural network for feature selection and uncovers intricate gene regulatory networks without requiring prior knowledge. Comprehensive evaluations on real-world datasets, including COVID-19 CITE-Seq and LUAD scRNA-Seq, demonstrate scSniper's exceptional ability to identify critical biomarkers consistently outperforming traditional methods like MAST, Wilcox, and DESeq2.The scSniper tool and related experimental codes are publicly accessible at https://github.com/mcgilldinglab/scSniper.
- Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile -
SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics and disulfide bonding of recombinant spike proteins derived from the SARS-CoV-2 Omicron variant (B.1.1.529) in comparison with the D614G spike variant. Furthermore, we conducted microsecond-long molecular dynamics simulations on spike proteins to resolve how the different N-glycans impact spike conformational sampling in the two variants. Our findings reveal that the Omicron spike protein maintains an overall resemblance to the D614G spike variant in terms of site-specific glycan processing and disulfide bond formation. Nonetheless, alterations in glycans were observed at certain N-glycosylation sites. These changes, in synergy with mutations within the Omicron spike protein, result in increased surface accessibility of the macromolecule, including ectodomain, receptor-binding domain, and N-terminal domain. These insights contribute to our understanding of the interplay between structure and function, thereby advancing effective vaccination and therapeutic strategies.
- Assembly reactions of SARS-CoV-2 nucleocapsid protein with nucleic acid -
The viral genome of SARS-CoV-2 is packaged by the nucleocapsid (N-)protein into ribonucleoprotein particles (RNPs), 38+/-10 of which are contained in each virion. Their architecture has remained unclear due to the pleomorphism of RNPs, the high flexibility of N-protein intrinsically disordered regions, and highly multivalent interactions between viral RNA and N-protein binding sites in both N-terminal (NTD) and C-terminal domain (CTD). Here we explore critical interaction motifs of RNPs by applying a combination of biophysical techniques to mutant proteins binding different nucleic acids in an in vitro assay for RNP formation, and by examining mutant proteins in a viral assembly assay. We find that nucleic acid-bound N-protein dimers oligomerize via a recently described protein-protein interface presented by a transient helix in its long disordered linker region between NTD and CTD. The resulting hexameric complexes are stabilized by multi-valent protein-nucleic acid interactions that establish crosslinks between dimeric subunits. Assemblies are stabilized by the dimeric CTD of N-protein offering more than one binding site for stem-loop RNA. Our study suggests a model for RNP assembly where N-protein scaffolding at high density on viral RNA is followed by cooperative multimerization through protein-protein interactions in the disordered linker.
- Predicting Antibody and ACE2 Affinity forSARS-CoV-2 BA.2.86 with In Silico ProteinModeling and Docking -
The emergence of the Omicron sublineage of SARS-CoV-2 virus BA.2.86 (nicknamed "Pirola") has raised concerns about its potential impact on public health and personal health as it has many mutations with respect to previous variants. We conducted an in silico analysis of neutralizing antibody binding to BA.2.86. Selected antibodies came from patients who were vaccinated and/or infected. We predicted binding affinity between BA.2.86 and antibodies. We also predicted the binding affinity between the same antibodies and several previous SARS-CoV2 variants (Wuhan and Omicron descendants BA.1, BA.2, and XBB.1.5). Additionally, we examined binding affinity between BA.2.86 and human angiotensin converting enzyme 2 (ACE2) receptor, a cell surface protein crucial for viral entry. We found no statistically significant difference in binding affinity between BA.2.86 and other variants, indicating a similar immune response. These findings contradict media reports of BA.2.86's high immune evasion potential based on its mutations. We discuss the implications of our findings and highlight the need for modeling and docking studies to go above and beyond mutation and basic serological neutralization analysis. Future research in this area will benefit from increased structural analyses of memory B-cell derived antibodies and should emphasize the importance of choosing appropriate samples for in silico studies to assess protection provided by vaccination and infection. This research contributes to understanding the BA.2.86 variant's potential impact on public health. Moreover, we introduce new methodologies for predictive medicine in ongoing efforts to combat the evolving SARS-CoV-2 pandemic and prepare for other hazards.
- Development of attenuated coxsackievirus B3 vectored intranasal pre-emptive pan-coronavirus vaccine -
SARS-CoV-2 has the ability to evade immunity, resulting in breakthrough infections even after vaccination. Similarly, zoonotic coronaviruses pose a risk of spillover to humans. There is an urgent need to develop a pre-emptive pan-coronavirus vaccine that can induce systemic and mucosal immunity. Here, we employed a combination of immune-informatics approaches to identify shared immunodominant linear B- and T-cell epitopes from SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs), as well as zoonotic coronaviruses. Epitope-guided vaccine were designed and the attenuated coxsackievirus B3 vectored intranasal vaccines rCVB3-EPI and rCVB3-RBD-trimer were constructed. The immunogenicity of these candidate vaccines was evaluated using Balb/c mice. The results demonstrated effective immune responses, including the production of SARS-CoV-2-specific IgG and sIgA antibodies, as well as T cell-mediated responses. However, further verification is required to assess cross-reactivity with various variants. Our intranasal pre-emptive pan-coronavirus vaccine design framework offers an appealing candidate for future vaccine development.
- Building energy use in COVID-19 lockdowns: did much change? -
The UK national lockdowns introduced to prevent the spread of COVID-19 had huge impacts on daily lives, as people were largely confined to their homes. It could be expected that residential energy use would drastically increase while non-residential decreased, however the picture is not so clear. In this paper three complementary datasets on different scales are used to explore changes in building energy use during two national lockdowns (spring 2020 and winter 2021): the complete building stock of Great Britain, a sample of ~1000 residential buildings, and a sample of ~24,000 residential boilers. Energy signature analysis was used for the building data to estimate the changes in energy consumption for space heating and otherwise, with the boiler data able to separate space and water heating and explore changes in these. In the 2020 lockdown residential energy consumption for water heating and appliances increased, with decreased use for heating, resulting in a reduction in total energy use during the heating season. In the 2021 lockdown total energy consumption changed little, however a decrease in the use of gas space heating was observed. These residential changes counteracted any non-domestic changes, resulting in little difference in national energy consumption.
- Tertiary folds of the SL5 RNA from the 5’ proximal region of SARS-CoV-2 and related coronaviruses -
Coronavirus genomes sequester their start codons within stem-loop 5 (SL5), a structured, 5' genomic RNA element. In most alpha- and betacoronaviruses, the secondary structure of SL5 is predicted to contain a four-way junction of helical stems, some of which are capped with UUYYGU hexaloops. Here, using cryogenic electron microscopy (cryo-EM) and computational modeling with biochemically-determined secondary structures, we present three-dimensional structures of SL5 from six coronaviruses. The SL5 domain of betacoronavirus SARS-CoV-2, resolved at 4.7 [A] resolution, exhibits a T-shaped structure, with its UUYYGU hexaloops at opposing ends of a coaxial stack, the T's "bar." Further analysis of SL5 domains from SARS-CoV-1 and MERS (7.1 and 6.4-6.9 [A] resolution, respectively) indicate that the junction geometry and inter-hexaloop distances are conserved features across the studied human-infecting betacoronaviruses. The MERS SL5 domain displays an additional tertiary interaction, which is also observed in the non-human-infecting betacoronavirus BtCoV-HKU5 (5.9-8.0 [A] resolution). SL5s from human-infecting alphacoronaviruses, HCoV-229E and HCoV-NL63 (6.5 and 8.4-9.0 [A] resolution, respectively), exhibit the same coaxial stacks, including the UUYYGU-capped bar, but with a phylogenetically distinct crossing angle, an X-shape. As such, all herein studied SL5 domains fold into stable tertiary structures with cross-genus similarities, with implications for potential protein-binding modes and future therapeutic targets.
- Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model -
Since 2002, three novel coronavirus outbreaks have occurred: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. A better understanding of the transmission potential of coronaviruses will result in adequate infection control precautions and an early halt of transmission within the human population. Experiments on the stability of coronaviruses in the environment, as well as transmission models, are thus pertinent. Here, we show that transgenic mice expressing human DPP4 can be infected with MERS-CoV via the aerosol route. Exposure to 5x106 TCID50 and 5x104 TCID50 MERS-CoV per cage via fomites resulted in transmission in 15 out of 20 and 11 out of 18 animals, respectively. Exposure of sentinel mice to donor mice one day post inoculation with 105 TCID50 MERS-CoV resulted in transmission in 1 out of 38 mice via direct contact and 4 out of 54 mice via airborne contact. Exposure to donor mice inoculated with 104 TCID50 MERS-CoV resulted in transmission in 0 out of 20 pairs via direct contact and 0 out of 5 pairs via the airborne route. Our model shows limited transmission of MERS-CoV via the fomite, direct contact, and airborne routes. The hDPP4 mouse model will allow assessment of the ongoing evolution of MERS-CoV in the context of acquiring enhanced human-to-human transmission kinetics and will inform the development of other transmission models.
- SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback -
Therapeutic anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been extensively studied in humans, but the impact on immune memory of mAb treatment during an ongoing immune response has remained unclear. Here, we evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes. Furthermore, the relative affinity of RBD memory B cells was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific defect in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating human memory B cell responses, both to infection and vaccination. These data indicate that mAb administration can promote alterations in the epitopes recognized by the B cell repertoire, and the single administration of mAb can continue to determine the fate of B cells in response to additional antigen exposures months later.
Collection of Additional Biological Samples From Potentially COVID-19 Patients for Monitoring of Biological Parameters Carried Out as Part of the Routine - Conditions: SARS CoV 2 Infection
Interventions: Diagnostic Test: RIPH2
Sponsors: CerbaXpert
Not yet recruiting
Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach - Conditions: Social Determinants of Health; Mental Health Issue; COVID-19
Interventions: Behavioral: Individual counseling; Behavioral: Group counseling; Other: Resources
Sponsors: Idaho State University
Not yet recruiting
Promoting Engagement and COVID-19 Testing for Health - Conditions: COVID-19
Interventions: Behavioral: COVID-19 Test Reporting; Behavioral: Personalized Nudges via Text Messaging; Behavioral: Non-personalized Nudges via Text Messaging
Sponsors: Emory University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Morehouse School of Medicine; Georgia Institute of Technology
Not yet recruiting
Development and Qualification of Methods for Analyzing the Mucosal Immune Response to COVID-19 - Conditions: Certain Disorders Involving the Immune Mechanism
Interventions: Biological: Sampling; Biological: PCR (polymerase chain reaction) SARS-CoV-2
Sponsors: University Hospital, Tours
Not yet recruiting
Water-based Activity to Enhance Recovery in Long COVID - Conditions: Long COVID
Interventions: Behavioral: WATER+CT; Behavioral: Usual Care
Sponsors: VA Office of Research and Development
Not yet recruiting
Performance Evaluation of the Lucira COVID-19 & Flu Test - Conditions: COVID-19; Influenza
Interventions: Device: Lucira COVID-19 & Flu Test
Sponsors: Lucira Health Inc
Completed
Efficacy of Two Therapeutic Exercise Modalities for Patients With Persistent COVID - Conditions: Persistent COVID-19
Interventions: Other: exercise programe
Sponsors: Facultat de ciencies de la Salut Universitat Ramon Llull
Recruiting
Robotic Assisted Hand Rehabilitation Outcomes in Adults After COVID-19 - Conditions: Robotic Exoskeleton; Post-acute Covid-19 Syndrome; Rehabilitation Outcome; Physical And Rehabilitation Medicine
Interventions: Device: Training with a Robotic Hand Exoskeleton
Sponsors: University of Valladolid; Centro Hospitalario Padre Benito Menni
Completed
Cognitive Rehabilitation in Post-COVID-19 Syndrome - Conditions: Post-COVID-19 Syndrome
Interventions: Behavioral: CO-OP Procedures; Behavioral: Inactive Control Group
Sponsors: University of Missouri-Columbia; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not yet recruiting
Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in Adults 18 Through 64 Years of Age - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Biological: BNT162b2; Other: Placebo; Biological: Seasonal Inactivated Influenza Vaccine
Sponsors: Pfizer
Completed
Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel - Conditions: COVID-19; Influenza A; Influenza B
Interventions: Diagnostic Test: Panbio™
Sponsors: Abbott Rapid Dx
Recruiting
A Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial - Conditions: Long COVID-19 Syndrome; Chronic Fatigue Syndrome
Interventions: Drug: Fluvoxamine Maleate 100 MG; Drug: Placebo; Drug: Metformin Extended Release Oral Tablet
Sponsors: Cardresearch
Recruiting
Connecting Friends and Health Workers to Boost COVID-19 Vaccination in Latino Communities - Conditions: COVID-19; Vaccine
Interventions: Behavioral: REDES; Behavioral: Control
Sponsors: Johns Hopkins University; National Institute on Minority Health and Health Disparities (NIMHD); Rutgers University
Recruiting
Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes - Conditions: Normobaric Hypoxia; Hypoventilation; Normoxia
Interventions: Other: Repeated sprint
Sponsors: Faculdade de Motricidade Humana; University of Sao Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Not yet recruiting
The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray - Conditions: SARS-CoV-2; Prevention
Interventions: Biological: A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray; Other: A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient
Sponsors: The Second Affiliated Hospital of Chongqing Medical University
Recruiting
Predictions based on inflammatory cytokine profiling of Egyptian COVID-19 with 2 potential therapeutic effects of certain marine-derived compounds - CONCLUSION: The investigated inflammatory biomarkers in Egyptian COVID-19 patients showed a strong correlation between IL6, TNF-α, NF-κB, CRB, DHL, and ferritin as COVID-19 biomarkers and determined the severity of the infection. Also, the oxidative /antioxidant showed good biomarkers for infection recovery and progression of the patients.
Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens - The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin-phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag….
Comparative Immune Response after Vaccination with SOBERANA® 02 and SOBERANA® plus Heterologous Scheme and Natural Infection in Young Children - (1) Background: In children, SARS-CoV-2 infection is mostly accompanied by mild COVID-19 symptoms. However, multisystem inflammatory syndrome (MIS-C) and long-term sequelae are often severe complications. Therefore, the protection of the pediatric population against SARS-CoV-2 with effective vaccines is particularly important. Here, we compare the humoral and cellular immune responses elicited in children (n = 15, aged 5-11 years) vaccinated with the RBD-based vaccines SOBERANA^(®) 02 and…
Screening Drugs for Broad-Spectrum, Host-Directed Antiviral Activity: Lessons from the Development of Probenecid for COVID-19 - In the early stages of drug discovery, researchers develop assays that are compatible with high throughput screening (HTS) and structure activity relationship (SAR) measurements. These assays are designed to evaluate the effectiveness of new and known molecular entities, typically targeting specific features within the virus. Drugs that inhibit virus replication by inhibiting a host gene or pathway are often missed because the goal is to identify active antiviral agents against known viral…
Covalent Inhibitors from Saudi Medicinal Plants Target RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2 - COVID-19, a disease caused by SARS-CoV-2, has caused a huge loss of human life, and the number of deaths is still continuing. Despite the lack of repurposed drugs and vaccines, the search for potential small molecules to inhibit SARS-CoV-2 is in demand. Hence, we relied on the drug-like characters of ten phytochemicals (compounds 1-10) that were previously isolated and purified by our research team from Saudi medicinal plants. We computationally evaluated the inhibition of RNA-dependent RNA…
Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters - Pibrentasvir (PIB) has been demonstrated to block exonuclease activity of the SARS-CoV-2 polymerase, protecting favipiravir (FVP) and remdesivir (RDV) from post-incorporation excision and eliciting antiviral synergy in vitro. The present study investigated the chemoprophylactic efficacy of PIB, FVP, RDV, FVP with PIB, or RDV with PIB dosed intranasally twice a day, using a Syrian golden hamster contact transmission model. Compared to the saline control, viral RNA levels were significantly lower…
SARS-CoV-2 Papain-like Protease Negatively Regulates the NLRP3 Inflammasome Pathway and Pyroptosis by Reducing the Oligomerization and Ubiquitination of ASC - The interaction of viruses with hosts is complex, especially so with the antiviral immune systems of hosts, and the underlying mechanisms remain perplexing. Infection with SARS-CoV-2 may result in cytokine syndrome in the later stages, reflecting the activation of the antiviral immune response. However, viruses also encode molecules to negatively regulate the antiviral immune systems of hosts to achieve immune evasion and benefit viral replication during the early stage of infection. It has been…
Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E - Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely,…
Development and Evaluation of a Self-Nanoemulsifying Drug Delivery System for Sinapic Acid with Improved Antiviral Efficacy against SARS-CoV-2 - This study aimed to develop a self-nanoemulsifying drug delivery system (SNE) for sinapic acid (SA) to improve its solubility and antiviral activity. Optimal components for the SA-SNE formulation were selected, including Labrafil as the oil, Cremophor EL as the surfactant, and Transcutol as the co-surfactant. The formulation was optimized using surface response design, and the optimized SA-SNE formulation exhibited a small globule size of 83.6 nm, high solubility up to 127.1 ± 3.3, and a 100%…
Effect of a Total Extract and Saponins from Astragalus glycyphyllos L. on Human Coronavirus Replication In Vitro - Members of the family Coronaviridae cause diseases in mammals, birds, and wildlife (bats), some of which may be transmissible to humans or specific to humans. In the human population, they can cause a wide range of diseases, mainly affecting the respiratory and digestive systems. In the scientific databases, there are huge numbers of research articles about the antiviral, antifungal, antibacterial, antiviral, and anthelmintic activities of medicinal herbs and crops with different ethnobotanical…
Kaempferol: A Review of Current Evidence of Its Antiviral Potential - Kaempferol and its derivatives are flavonoids found in various plants, and a considerable number of these have been used in various medical applications worldwide. Kaempferol and its compounds have well-known antioxidant, anti-inflammatory and antimicrobial properties among other health benefits. However, the antiviral properties of kaempferol are notable, and there is a significant number of experimental studies on this topic. Kaempferol compounds were effective against DNA viruses such as…
Unwinding the SARS-CoV-2 Ribosomal Frameshifting Pseudoknot with LNA and G-Clamp-Modified Phosphorothioate Oligonucleotides Inhibits Viral Replication - Ribosomal frameshifting (RFS) at the slippery site of SARS-CoV-2 RNA is essential for the biosynthesis of the viral replication machinery. It requires the formation of a pseudoknot (PK) structure near the slippery site and can be inhibited by PK-disrupting oligonucleotide-based antivirals. We obtained and compared three types of such antiviral candidates, namely locked nucleic acids (LNA), LNA-DNA gapmers, and G-clamp-containing phosphorothioates (CPSs) complementary to PK stems. Using optical…
Herbal Compounds Dauricine and Isoliensinine Impede SARS-CoV-2 Viral Entry - Targeting viral entry has been the focal point for the last 3 years due to the continued threat posed by SARS-CoV-2. SARS-CoV-2’s entry is highly dependent on the interaction between the virus’s Spike protein and host receptors. The virus’s Spike protein is a key modulator of viral entry, allowing sequential cleavage of ACE2 at the S1/S2 and S2 sites, resulting in the amalgamation of membranes and subsequent entry of the virus. A Polybasic insertion (PRRAR) conveniently located at the S1/S2 site…
Evaluation of A-ring hydroxymethylene-amino- triterpenoids as inhibitors of SARS-CoV-2 spike pseudovirus and influenza H1N1 - A set of triterpene A-ring hydroxymethylene-amino-derivatives was synthesized and their antiviral activity was studied. The synthesized compounds were tested for their potential inhibition of SARS-CoV-2 pseudovirus in BHK-21-hACE2 cells and influenza A/PuertoRico/8/34 (H1N1) virus in MDCK cell culture. Compounds 6, 8 and 19 showed significant anti-SARS-CoV-2 pseudovirus activity with EC(50) value of 3.20-11.13 µM, which is comparable to the positive control amodiaquine (EC(50) 3.17 µM). Among…
Applications of peptide-functionalized or unfunctionalized selenium nanoparticles for the passivation of SARS-CoV-2 variants and the respiratory syncytial virus (RSV) - The SARS-CoV-2 Omicron subvariants BA.4, BA. 5 and XBB are currently causing a COVID resurgence due to their increased spreading and infectivity. These latest subvariants have been shown to be somewhat resistant to the most common vaccines even with the third dose. Moreover, it has been well documented that when patients stop taking some commercial therapies (such as Paxlovid), COVID from these variants may return and may even be more contagious. Herein, we tested unfunctionalized and…