- Protein-based cell population discovery and annotation for CITE-seq data identifies cellular phenotypes associated with critical COVID-19 severity -
Technologies such as Cellular Indexing of Transcriptomes and Epitopes sequencing (CITE-seq) and RNA Expression and Protein sequencing (REAP-seq) augment unimodal single-cell RNA sequencing (scRNA-seq) by simultaneously measuring expression of cell-surface proteins using antibody derived oligonucleotide tags (ADT). These protocols have been increasingly used to resolve cellular populations that are difficult to infer from gene expression alone, and to interrogate the relationship between gene and protein expression at a single-cell level. However, the ADT-based protein expression component of these assays remains widely underutilized as a primary tool to discover and annotate cell populations, in contrast to flow cytometry which has used surface protein expression in this fashion for decades. Therefore, we hypothesized that computational tools used for flow cytometry data analysis could be harnessed and scaled to analyze ADT data. Here we apply Ozette Discovery, a recently-developed method for flow cytometry analysis, to re-analyze a large (>400,000 cells) published COVID-19 CITE-seq dataset. Using the protein expression data alone, Ozette Discovery is able to identify granular, robust, and interpretable cellular phenotypes in a high-throughput manner. In particular, we identify a population of CLEC12A+CD11b+CD14- myeloid cells that are specifically expanded in patients with critical COVID-19, and can only be resolved by their protein expression profiles. Using the longitudinal gene expression data from this dataset, we find that early expression of interferon response genes precedes the expansion of this subset, and that early expression of PRF1 and GZMB within specific Ozette Discovery phenotypes provides a RNA biomarker of critical COVID-19. In summary, Ozette Discovery demonstrates that taking a protein-centric approach to cell phenotype annotation in CITE-seq data can achieve the potential that dual RNA/protein assays provide in mixed samples: instantaneous in silico flow sorting, and unbiased RNA-seq profiling.
- Differential Patterns of Cross-Protection against Antigenically Distinct Variants in Small Animal Models of SARS-CoV-2 Infection -
Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will likely force more future updates of vaccine composition. Based on a series of studies carried out in human ACE2 transgenic mice (K18-hACE2) and Syrian hamsters, we show that immunity at the respiratory tract, acquired through either previous infection or vaccination with an in-house live attenuate virus, offers protection against antigenically distinct variants in the absence of variant spike-specific neutralizing antibodies. Interestingly, immunity acquired through infection of a modern variant (XBB.1.5) was insufficient in preventing brain infection by the ancestral virus (WA1/2020) in K18-hACE2 mice. Similarly, previous infection with WA1/2020 did not protect against brain infection by XBB.1.5. Our results highlight the importance of immune components other than neutralizing antibodies in maintaining protection against new variants in the respiratory tract, but also paint scenarios where a monovalent vaccine based on a contemporary variant may be less effective against the ancestral strain.
- ONE HEALTH APPROACH ON SARS-COV-2 - USING SHEEP AS SENTINEL ANIMALS TO INCREASE FUTURE PANDEMIC PREPAREDNESS - a pilot study -
Coronaviruses are a family of viruses that can infect a number of species of birds and mammals with great zoonotic potential to cross species barriers and cause spill-over events. SARS-CoV-2 has been shown to cause clinical and inapparent disease and mortality in several animals cohabitating with humans. Sheep are also susceptible to SARS-CoV-2 and have potential to harbor and spread the virus, as well as develop neutralising antibodies due to similarities of virus-receptor interactions to those in humans. The main aim of this study was to investigate the prevalence of SARS-CoV-2 neutralising antibodies in sentinel animals after natural exposure to the virus. The serum samples were collected from sheep in Central Portugal, Serra da Estrela region, both prior to and during the COVID-19 pandemic. The sheep were kept on dairy farms for production of Serra da Estrela cheese, in small herds and in constant contact with farm workers. The sera were tested using already established SARS-CoV-2 pseudovirus systems for multiple SARS-CoV-2 variants including Wuhan, Delta and Omicron. Partial neutralisation activity towards Wuhan and Delta variants was observed, while neutralisating antibody escape was observed in all Omicron variants tested due to the mutations present . Our results indicate that potential SARS-CoV-2 virus cross-species transmission could have been established through contacts between people and animals on sheep farms. Using farm animals as sentinels is of great importance for implementing One Health Approach in zoonotic virus surveillance and control towards increasing future pandemic preparedness.
- de Novo Sequencing of Antibodies for Identification of Neutralizing Antibodies in Human Plasma Post SARS-CoV-2 Vaccination -
We present a method for sequencing polyclonal IgG enriched from human plasma, employing a combination of de novo sequencing, proteomics, bioinformatics, protein separation, sequencing, and peptide separations. Our study analyzes a single patient's IgG antibody response triggered by the Moderna Spikevax mRNA COVID-19 vaccine. From the sequencing data of the natural polyclonal response to vaccination, we generated 12 recombinant antibodies. Six derived recombinant antibodies, including four generated with de novo sequencing, exhibited similar or higher binding affinities than the original natural polyclonal antibody. Our neutralization tests revealed that the six antibodies possess neutralizing capabilities against the target antigen. This research provides insights into sequencing polyclonal IgG antibodies while highlighting the effectiveness and potential of our approach in generating recombinant antibodies with robust binding affinity and neutralization capabilities. Our proposed approach is an advancement in characterizing the IgG response by directly investigating the circulating pool of IgG without relying exclusively on the B-cell repertoire or population. This is crucial as the B-cell analysis may not accurately represent the circulating antibodies. Interestingly, a large proportion (80 to 90%) of the human antibody sequences generated against SARS-CoV-2 in the literature have been derived solely from B-cell analysis. Therefore, the ability to offer a different perspective is crucial in gaining a comprehensive understanding of the IgG response.
- Case of Myocarditis, Pericarditis, and Fatal Aortic Dissection following Covid-19 mRNA Vaccination -
We present a case study of a 34-year-old male who was in good health prior to his COVID-19 mRNA vaccination. Sixteen days after his first dose, he experienced acute inflammation, sudden thoracic aortic dissection, and pericardial tamponade, rapidly leading to his death. Studies suggest that young males, in particular, appear to be at increased risk of adverse cardiac events following COVID-19 mRNA vaccination. Although the incidence of such complications are believed to be low, we propose that information gaps exist in the criteria and findings that inform both public health agencies and the public on incidence rates of even severe myocarditis and cardiac adverse events following COVID-19 vaccination. This view is shared within many COVID-19 vaccine myocarditis studies and is evident within the findings of this case of Myocarditis, Pericarditis, and Fatal Aortic Dissection presented here.
- SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion -
The COVID-19 pandemic is caused by SARS-CoV-2, an enveloped RNA virus. Despite extensive investigation, the molecular mechanisms for its assembly and secretion remain largely elusive. Here, we show that SARS-CoV-2 infection induces global alterations of the host endomembrane system, including dramatic Golgi fragmentation. SARS-CoV-2 virions are enriched in the fragmented Golgi. Disrupting Golgi function with small molecules strongly inhibits viral infection. Significantly, SARS-CoV-2 infection down-regulates GRASP55 but up-regulates TGN46 protein levels. Surprisingly, GRASP55 expression reduces both viral secretion and spike number on each virion, while GRASP55 depletion displays opposite effects. In contrast, TGN46 depletion only inhibits viral secretion without affecting spike incorporation into virions. TGN46 depletion and GRASP55 expression additively inhibit viral secretion, indicating that they act at different stages. Taken together, we show that SARS-CoV-2 alters Golgi structure and function to control viral assembly and secretion, highlighting the Golgi as a potential therapeutic target for blocking SARS-CoV-2 infection.
- Exploring associations between the Covid-19 vaccination campaign and fertility trends: A population-level analysis for 22 countries -
Background At the turn of 2021-2022, monthly birth rates declined in many higher-income countries. We explore how the rollout of COVID-19 vaccination was associated with this decline. Methods Using an interrupted time series design, we evaluate the impact of the onset of the COVID-19 pandemic and the start of COVID-19 vaccination on seasonally-adjusted monthly total fertility rates in 22 high-income countries. We study the associations between COVID-19 vaccination and fertility by additionally controlling for youth unemployment, stringency index, and vaccination coverage. Results The start of the pandemic had an immediate effect on fertility in most countries, although the size and direction of level changes considerably varied across countries. The impact of COVID-19 vaccination was less all-embracing. A negative association between the COVID-19 vaccine rollout and fertility nine months later was found for ten out of 22 countries. For several countries, the decline was preceded by fertility increase that took place after the onset of the pandemic. Only four of 22 countries had post-vaccination fertility declines that resulted in fertility being on a lower level than what the pre-pandemic trend predicted. Additional control variables changed the associations only little. Conclusions The COVID-19 vaccination campaign contributed to the variation in the short-term fertility trends. Several countries experienced declines following the campaign, however, this decline often returned fertility closer to the pre-pandemic trend. Fertility appears to have responded in short run to vaccination, but only in few cases such that the long-term trajectory is below the pre-pandemic trend.
- Urban birds’ tolerance towards humans was largely unaffected by increased variation in human levels due to COVID-19 shutdowns -
The coronavirus disease 2019 (COVID-19) pandemic dramatically altered human activities, and, during shutdowns, potentially changed human pressures on urban-dwelling animals. Here, we evaluated whether urban birds from five countries (Finland, Poland, Czech Republic, Hungary, Australia) changed their tolerance towards humans (measured as flight initiation distance) during the COVID-19 shutdowns. We collected 6369 flight initiation distance estimates for 147 bird species and found that human numbers in parks (at a given hour, day, week or year - before and during the COVID-19 shutdowns) had a little effect on birds tolerance of approaching humans. Apart from the actual human numbers in the area (hourly temporal scale) - which as expected correlated negatively, albeit weakly, with escape distance - the effect of human activity at other temporal scales centered around zero. The results were similar across countries, for most species or when we restricted our analyses only to species sampled both before and during the COVID-19 shutdowns. As expected, the level of daily human presence in parks (measured by Google Mobility Reports) correlated negatively with the stringency of governmental restrictions (a weekly proxy for human presence) and was overall lower during COVID-19 shutdowns than during the post-shutdown year (2022). Our results highlight the resilience of birds to changes in human numbers on multiple temporal scales, the complexities of linking animal fear responses to human behavior, and the challenge of quantifying both simultaneously in situ.
- Escherichia coli grown in cost-effective conical tubes produces more plasmid DNA -
Before the COVID-19 pandemic, we grew plasmid-transformed Escherichia coli in Falcon round-bottom-polypropylene tubes (F-Round-PP) and isolated plasmid using a Miniprep kit. When obtaining sufficient quantities of F-Round-PP became problematic during the pandemic and the inflation, we grew them using any available tubes. Notably, we observed that plasmid yield from cells grown in a cost-effective Oxford conical-polypropylene tubes (O-Conical-PP) was higher than that from F-Round-PP. We assessed the impact using O-Conical-PP and other conical brand tubes. As a result, the plasmid yield from O-Conical-PP (the list price is nearly 1/3 of F-Round-PP) was 1.5-fold higher than other PP tubes (p<0.001). We propose that researchers may need to re-assess the effectiveness of their laboratory supplies to optimize the budget during this inflationary period.
- Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV -
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and has therefore been the focus of vaccine design efforts. Currently there are no licensed vaccines against MERS-CoV and only a few candidates have advanced to Phase I clinical trials. Here we developed MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for SARS-CoV-2. Two-component protein nanoparticles displaying MERS-CoV S-derived antigens induced robust neutralizing antibody responses and protected mice against challenge with mouse-adapted MERS-CoV. Electron microscopy polyclonal epitope mapping and serum competition assays revealed the specificities of the dominant antibody responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle vaccine elicited antibodies targeting multiple non-overlapping epitopes in the RBD, whereas anti-NTD antibodies elicited by the S-2P- and NTD-based immunogens converged on a single antigenic site. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.
- Self-inhibiting percolation and viral spreading in epithelial tissue -
SARS-CoV-2 induces delayed type-I/III interferon production, allowing it to escape the early innate immune response. The delay has been attributed to a deficiency in the ability of cells to sense viral replication upon infection, which in turn hampers activation of the antiviral state in bystander cells. Here, we introduce a cellular automaton model to investigate the spatiotemporal spreading of viral infection as a function of virus and host-dependent parameters. The model suggests that the considerable person-to-person heterogeneity in SARS-CoV-2 infections is a consequence of high sensitivity to slight variations in biological parameters near a critical threshold. It further suggests that within-host viral proliferation can be curtailed by the presence of remarkably few cells that are primed for IFN production. Thus the observed heterogeneity in defense readiness of cells reflects a remarkably cost-efficient strategy for protection.
- Engineered Migrasomes: A Robust, Thermally Stable Vaccination Platform -
The burgeoning abilities of pathogens and tumor cells to evade immune responses underscore the urgent need for innovative vaccination platforms based on a variety of biological mechanisms. The current logistical challenges associated with cold-chain (i.e. low-temperature) transportation particularly impacts access to vaccines in the global south. We recently discovered organelles called migrasomes, and herein we investigate the potential of migrasomes as an alternative vaccination platform. Their inherent stability and their enrichment with immune-modulating molecules make migrasomes promising candidates, but their low yield presents a hurdle. We address this problem through our engineered migrasome-like vesicles (eMigrasomes), which emulate the biophysical attributes of natural migrasomes with substantially improved yield. We show that eMigrasomes loaded with a model antigen elicit potent antibody responses and maintain stability at room temperature. We demonstrate that eMigrasomes bearing the SARS-CoV-2 Spike protein induce robust humoral protection against the virus. Our study demonstrates the potential of eMigrasome-based vaccines as a unique, robust, and accessible alternative to traditional methods.
- CircRNA-Pro: A Novel Toolkit for High-Precision Detection of Differentially Expressed Circular RNAs and Translatable Circular RNAs -
With the increasing discovery of circular RNAs (circRNAs) and their critical roles in gene regulation and disease progression, there is a growing need for more accurate and efficient tools for circRNAs research. In response, we have developed an integrated software suite specifically for circRNAs. This all-in-one tool specializes in detecting differentially expressed circRNAs, including those with the potential to be translated into proteins, and allows for comparing against relevant databases, thereby enabling comprehensive circRNA profiling and annotation. To enhance the accuracy in detecting differentially expressed circRNAs, we incorporated three different software algorithms and cross-validated their results through mutual verification. Additionally, this toolkit improves the effectiveness in identifying translatable circRNAs by optimizing Ribo-seq alignment and verifying against public circRNA databases. The performance of circRNA-pro has been evaluated through its application to public RNA-seq and Ribo-seq datasets on breast cancer and SARS-CoV-2 infected cells, and the results obtained have been validated against previous literature and databases. Overall, our integrated toolkit provides a reliable workflow for circRNA research, facilitating insights into their diverse roles across life sciences.
- Mutability and hypermutation antagonize immunoglobulin codon optimality -
The efficacy of polyclonal antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation (SHM). These processes arose in early jawed vertebrates; however, little is known about how immunoglobulin diversity, mutability, and hypermutation have evolved in tandem with another more ubiquitous feature of protein-coding DNA - codon optimality. Here, we explore these relationships through analysis of germline IG genes, natural V(D)J repertoires, serum VH usage, and monoclonal antibody (mAb) expression, each through the lens of multiple optimality metrics. Strikingly, proteomic serum IgG sequencing showed that germline IGHV codon optimality positively correlated with VH representation after influenza vaccination, and in vitro, codon deoptimization of mAbs with synonymous amino acid sequences caused consistent expression loss. Germline V genes exhibit a range of codon optimality that is maintained by functionality, and inversely related to mutability. SHM caused a load-dependent deoptimization of IGH VDJ repertoires within human tonsils, bone marrow, and lymph nodes (including SARS-CoV-2-specific clones from mRNA vaccinees), influenza-infected mice, and zebrafish. Comparison of natural mutation profiles to true random suggests the presence of selective pressures that constrain deoptimization. These findings shed light on immunoglobulin evolution, providing unanticipated insights into the antagonistic relationship between variable region diversification, codon optimality, and antibody secretion; ultimately, the need for diversity takes precedence over that for the most efficient expression of the antibody repertoire.
- Understanding Young Caring in the UK Pre- and Post-COVID-19: Prevalence, Correlates, and Insights from Three UK Longitudinal Surveys -
Background. Despite increasing awareness of young carers in recent years, there remains a significant gap in our understanding of both the prevalence and the characteristics of young carers. Our study aims to address this gap by examining the impact of the COVID-19 pandemic on the prevalence and characteristics of young carers. Methods. This research utilised data from three UK longitudinal surveys: the UK Household Longitudinal Study (UKHLS), the COVID Social Mobility and Opportunities (COSMO) study, and the Millennium Cohort Study (MCS). We focused on adolescents aged 16-18, and examined two pre-COVID (UKHLS and MCS) and two post-COVID (UKHLS and COSMO) samples. Results. The prevalence of young carers increased from 8.0% pre-COVID to 9.8-11.9% since COVID. Young carers were more commonly found in single-parent and socioeconomically disadvantaged households, with a higher prevalence of young carers in homes where parents were out of paid employment or held lower educational qualifications. Young carers were also more likely to reside in deprived areas. Most young carers engaged in low-intensity caring (< 10 hours/week), but post-COVID there was an increase in high-intensity caring (10+ hours/week), predominantly assumed by young female carers. The primary recipients of care were parents, followed by grandparents and siblings, with no change in the care recipient type since COVID. Conclusion. This study showed an increase in the prevalence of young carers, particularly those providing high-intensity care, since the onset of the COVID pandemic. Further, young carers were more likely to come from socioeconomically disadvantaged households and areas. Given the potential impacts that young caring can have on young peoples’ lives, it is imperative that support for young carers is increased, particularly for those facing multiple disadvantages. In tandem, services that support adult health and social care need to play a key role in identifying young carers.
Utilizing Novel Blood RNA Biomarkers as a Diagnostic Tool in the Identification of Long COVID-19 - Conditions: Long COVID
Interventions: Diagnostic Test: RNA Biomarker Blood Test
Sponsors: MaxWell Clinic, PLC
Recruiting
Home-Based Circuit Training in Overweight/Obese Older Adult Patients With Knee Osteoarthritis and Type 2 Diabetes - Conditions: Aerobic Exercise; Strength Training; Glycemic Control; Blood Pressure; Oxidative Stress; Metabolic Syndrome
Interventions: Behavioral: 12-week home-based circuit training (HBCT); Behavioral: Standard of care (CONT)
Sponsors: Princess Nourah Bint Abdulrahman University
Completed
RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine) - Conditions: Long COVID; Long Covid19; Long Covid-19
Interventions: Drug: Ivabradine; Drug: Ivabradine Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care
Sponsors: Kanecia Obie Zimmerman
Enrolling by invitation
SVF for Treating Pulmonary Fibrosis Post COVID-19 - Conditions: Pulmonary Fibrosis
Interventions: Biological: Autologous adipose-derived SVF IV administration
Sponsors: Michael H Carstens; Ministerio de Salud de Nicaragua; Wake Forest University; National Autonomous University of Nicaragua
Completed
RECOVER-AUTONOMIC Platform Protocol - Conditions: Long COVID; Long Covid19; Long Covid-19
Interventions: Drug: IVIG + Coordinated Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG Placebo + Usual Care; Drug: Ivabradine + Usual Care; Drug: Ivabradine Placebo + Usual Care
Sponsors: Kanecia Obie Zimmerman
Enrolling by invitation
RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG) - Conditions: Long COVID; Long Coronavirus Disease 2019 (Covid19); Long Covid-19
Interventions: Drug: IVIG (intravenous immunoglobulin); Drug: IVIG Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care
Sponsors: Kanecia Obie Zimmerman
Not yet recruiting
Understanding Adaptive Immune Response After COVID-19 Vaccination Boosters to Improve Vaccination Strategies in Vulnerable Groups. - Conditions: COVID-19
Interventions: Other: Analisys of cellular response and humoral response to SARS-CoV-2 vaccine booster doses
Sponsors: IRCCS Sacro Cuore Don Calabria di Negrar
Recruiting
COVIDVaxStories: Randomized Trial to Reduce COVID-19 Vaccine Hesitancy in Populations of Color - Conditions: Vaccine Hesitancy
Interventions: Behavioral: Storytelling; Behavioral: Learn More (Active Comparator)
Sponsors: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC
Recruiting
Sulfureous Water Therapy in Viral Respiratory Diseases - Conditions: Long-COVID; Post COVID-19 Condition; Chronic COVID-19 Syndrome; Post Acute Sequelae of COVID-19
Interventions: Other: Inhalation of Sulfurous Thermal Water; Other: Inhalation of Sterile Distilled non-pyrogenic Water
Sponsors: University of Roma La Sapienza; Università degli studi di Roma Foro Italico; Queen Mary University of London; Bios Prevention Srl
Completed
An E-health Psychoeducation for People With Bipolar Disorders - Conditions: Bipolar Disorder; Psychoeducation; COVID-19 Pandemic
Interventions: Other: e-health psychoeducation
Sponsors: University of Cagliari; Alessandra Perra
Completed
Phase 3 Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine and Influenza Combination Vaccine - Conditions: COVID-19
Interventions: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection
Sponsors: Novavax
Not yet recruiting
Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection. - Conditions: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Interventions: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo)
Sponsors: Sheng-Teng Huang
Completed
A combination of nirmatrelvir and ombitasvir boosts inhibition of SARS-CoV-2 replication - Antiviral therapeutics are highly effective countermeasures for the treatment of coronavirus disease 2019 (COVID-19). However, development of resistance to antivirals undermines their effectiveness. Combining multiple antivirals during patient treatment has the potential to overcome the evolutionary selective pressure towards antiviral resistance, as well as provide a more robust and efficacious treatment option. The current evidence for effective antiviral combinations to inhibit severe acute…
Novel nitric oxide donors are coronary vasodilators that also bind to the papain-like protease of SARS-CoV-2 - Several investigational nitric oxide donors were originally created to correct vascular endothelial dysfunction in cardiovascular diseases. These 48 compounds contain an urea-like moiety attached to the well-known NO donors isosorbide 2- and 5-mononitrate. CR-0305 and CR-0202 were synthesized and found to be nontoxic in the cell lines HMEC-1, A549/hACE2 and VeroE6. CR-0305 induced vasodilation in human coronary arteries ex vivo. Since NO can also have antiviral properties, a study of…
Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication and pathogenicity - G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibits stress granule assembly and interacts with G3BP1/2 via an ITFG motif, including residue F17, in the N protein. Prior studies examining the impact of the G3PB1-N interaction on SARS-CoV-2 replication have produced inconsistent findings, and the role of this…
Eucalyptus Oils Phytochemical Composition in Correlation with Their Newly Explored Anti-SARS-CoV-2 Potential: in Vitro and in Silico Approaches - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the latest arisen contagious respiratory pathogen related to the global outbreak of atypical pneumonia pandemic (COVID-19). The essential oils (EOs) of Eucalyptus camaldulensis, E. ficifolia F. Muell., E. citriodora Hook, E. globulus Labill, E. sideroxylon Cunn. ex Woolls, and E. torquata Luehm. were investigated for its antiviral activity against SARS-CoV-2. The EOs phytochemical composition was determined using GC/MS analysis….
Drug repurposing screen to identify inhibitors of the RNA polymerase (nsp12) and helicase (nsp13) from SARS-CoV-2 replication and transcription complex - Coronaviruses contain one of the largest genomes among the RNA viruses, coding for 14-16 non-structural proteins (nsp) that are involved in proteolytic processing, genome replication and transcription, and four structural proteins that build the core of the mature virion. Due to conservation across coronaviruses, nsps form a group of promising drug targets as their inhibition directly affects viral replication and, therefore, progression of infection. A minimal but fully functional replication…
Favipiravir ameliorates bleomycin-induced pulmonary fibrosis by reprogramming M1/M2 macrophage polarization - Corona Virus Disease 2019 (COVID-19) is an infectious disease that seriously endangers human life and health. The pathological anatomy results of patients who died of the COVID-19 showed that there was an excessive inflammatory response in the lungs. It is also known that most of the COVID-19 infected patients will cause different degrees of lung damage after infection, and may have pulmonary fibrosis remaining after cure. Macrophages are a type of immune cell population with pluripotency and…
Potent HPIV3-neutralizing IGHV5-51 Antibodies Identified from Multiple Individuals Show L Chain and CDRH3 Promiscuity - Human parainfluenza virus 3 (HPIV3) is a widespread pathogen causing severe and lethal respiratory illness in at-risk populations. Effective countermeasures are in various stages of development; however, licensed therapeutic and prophylactic options are not available. The fusion glycoprotein (HPIV3 F), responsible for facilitating viral entry into host cells, is a major target of neutralizing Abs that inhibit infection. Although several neutralizing Abs against a small number of HPIV3 F epitopes…
2-Bromopalmitate depletes lipid droplets to inhibit viral replication - The global impact of emerging viral infections emphasizes the urgent need for effective broad-spectrum antivirals. The cellular organelle, lipid droplet (LD), is utilized by many types of viruses for replication, but its reduction does not affect cell survival. Therefore, LD is a potential target for developing broad-spectrum antivirals. In this study, we found that 2-bromopalmitate (2 BP), a previously defined palmitoylation inhibitor, depletes LD across all studied cell lines and exerts…
Utilizing sinapic acid as an inhibitory antiviral agent against MERS-CoV PLpro - Concerns about the social and economic collapse, high mortality rates, and stress on the healthcare system are developing due to the coronavirus onslaught in the form of various species and their variants. In the recent past, infections brought on by coronaviruses severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) as well as middle east respiratory syndrome coronavirus (MERS-CoV) have been reported. There is a severe lack of medications to treat various coronavirus types…
Recognition of granulocyte-macrophage colony-stimulating factor by specific S100 proteins - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic myelopoietic growth factor and proinflammatory cytokine, clinically used for multiple indications and serving as a promising target for treatment of many disorders, including cancer, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, COVID-19. We have previously shown that dimeric Ca^(2+)-bound forms of S100A6 and S100P proteins, members of the multifunctional S100 protein family, are specific to GM-CSF. To…
Developing inhibitory peptides against SARS-CoV-2 envelope protein - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected approximately 800 million people since the start of the Coronavirus Disease 2019 (COVID-19) pandemic. Because of the high rate of mutagenesis in SARS-CoV-2, it is difficult to develop a sustainable approach for prevention and treatment. The Envelope (E) protein is highly conserved among human coronaviruses. Previous studies reported that SARS-CoV-1 E deficiency reduced viral propagation, suggesting that E inhibition might…
Interactions among stress, behavioral inhibition, and delta-beta coupling predict adolescent anxiety during the COVID-19 pandemic - The COVID-19 pandemic brought about unprecedented changes and uncertainty to the daily lives of youth. The range of adjustment in light of a near-universal experience of COVID restrictions highlights the importance of identifying factors that may render some individuals more susceptible to heightened levels of anxiety during stressful life events than others. Two risk factors to consider are temperamental behavioral inhibition (BI) and difficulties in emotion regulation (ER). As such, the…
Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel - Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19…
Neutralization of SARS-CoV-2 and Intranasal Protection of Mice with a nanoCLAMP Antibody Mimetic - Intranasal treatment, combined with vaccination, has the potential to slow mutational evolution of viruses by reducing transmission and replication. Here, we illustrate the development of a SARS-CoV-2 receptor-binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope-binding nanoCLAMP, P2609. The resulting multimerized nanoCLAMP P2712 had…
Exploring cell-free assays for COVID-19 serosurvey - Serosurveys to monitor immunity toward COVID-19 in the population are primarily performed using an ELISA to screen samples for SARS-CoV-2 antibodies, followed by confirmation by a virus neutralization test, which is considered the Gold Standard. However, virus neutralization test may not be feasible for some laboratories because of the requirement for specific facilities and trained personnel. In an attempt to address this limitation, we evaluated three cell-free methods as potential…