- Forecasting dominance of SARS-CoV-2 lineages by anomaly detection using deep AutoEncoders -
The COVID-19 pandemic exemplified the need for a rapid, effective genomic-based surveillance system to predict emerging SARS-CoV-2 variants and lineages. Traditional molecular epidemiology methods, which leverage public health surveillance or integrated sequence data repositories, are able to characterize the evolutionary history of infection waves and genetic evolution but fall short in predicting future outlooks in promptly anticipating viral genetic alterations. To bridge this gap, we introduce a novel Deep learning, autoencoder-based method for anomaly detection in SARS-CoV-2 (DeepAutoCov). Trained and updated on the public global SARS-CoV-2 GISAID database. DeepAutoCov identifies Future Dominant Lineages (FDLs), defined as lineages comprising at least 25% of SARS-CoV-2 genomes added on a given week, on a weekly basis, using the Spike (S) protein. Our algorithm is grounded on anomaly detection via an unsupervised approach, which is necessary given that FDLs can be known only a posteriori (i.e., after they have become dominant). We developed two concurrent approaches (a linear unsupervised and a posteriori supervised) to evaluate DeepAutoCoV performance. DeepAutoCoV identifies FDL, using the spike (S) protein, with a median lead time of 31 weeks on global data and achieves a positive predictive value ~7x better and 23% higher than the other approaches. Furthermore, it predicts vaccine related FDLs up to 17 months in advance. Finally, DeepAutoCoV is not only predictive but also interpretable, since it can pinpoint specific mutations within FDLs, generating hypotheses on the potential increases in virulence or transmissibility of a lineage. By integrating genomic surveillance with artificial intelligence, our work marks a transformative step that may provide valuable insights for the optimization of public health prevention and intervention strategies.
- Nonspecific membrane bilayer perturbations by ivermectin underlie SARS-CoV-2 in vitro activity -
Since it was proposed as a potential host-directed antiviral agent for SARS-CoV-2, the antiparasitic drug ivermectin has been investigated thoroughly in clinical trials, which have provided insufficient support for its clinical efficacy. To examine the potential for ivermectin to be repurposed as an antiviral agent, we therefore undertook a series of preclinical studies. Consistent with early reports, ivermectin decreased SARS-CoV-2 viral burden in in vitro models at low micromolar concentrations, five- to ten-fold higher than the reported toxic clinical concentration. At similar concentrations, ivermectin also decreased cell viability and increased biomarkers of cytotoxicity and apoptosis. Further mechanistic and profiling studies revealed that ivermectin nonspecifically perturbs membrane bilayers at the same concentrations where it decreases the SARS-CoV-2 viral burden, resulting in nonspecific modulation of membrane-based targets such as G-protein coupled receptors and ion channels. These results suggest that a primary molecular mechanism for the in vitro antiviral activity of ivermectin may be nonspecific membrane perturbation, indicating that ivermectin is unlikely to be translatable into a safe and effective antiviral agent. These results and experimental workflow provide a useful paradigm for performing preclinical studies on (pandemic-related) drug repurposing candidates.
- Facemask wearing in COVID-19 pandemic: Correlates and prevalence; A survey after COVID-19 second wave in Uganda. -
Background: The WHO and the US. CDC documented that facemask-wearing in public situations is one of the most important prevention measures that can limit the acquisition and spread of COVID-19. Considering this, WHO and US. CDC developed guidelines for using facemasks in public settings. This study aimed to determine correlates and prevalence of facemask wearing during COVID-19 pandemic among adult population of Northern Uganda. Methods. We conducted a cross-sectional study on five hundred and eighty-seven adult population of northern Uganda. A single stage stratified, and systematic sampling methods were used to select respondents from twenty-four Acholi subregion’s health facilities. Data was collected in a face-to-face questionnaire interview with an internal validity of Cronbach9s α=0.72. A local IRB approved the study, and Stata 18 was used for data analysis at multivariable Poisson regression with a p-value set at ≤0.05. Results: The most substantial findings from this study were the high prevalence of face mask-wearing in public among respondents [88.7%,95%CI:86%-91%]. At a multivariable Poisson regression analysis, we found that obese respondents were 1.12 times more likely to wear facemasks than those who were not, [adjusted Interval Rates Ratios, aIRR=1.12,95%CI:1.04-1.19;p<0.01], and respondent who agreed to the lockdown measures were 1.23 times more likely to wear facemasks during COVID-19 pandemic than those who did not, [aIRR=1.23, 95%CI:1.07-1.41;p<0.01]. Other sociodemographic characteristics such as sex, age, occupation, level of education, religion, tribes, marital status, nationality, race, and comorbidities were not statistically significant at 95% Confidence Intervals. Conclusion: The most significant findings from this study were the high prevalence of face mask-wearing among adult community members in northern Uganda. The correlates of facemask wearing in public were the obese and respondents who agreed with the presidential directives on the lockdown measures. Although this was within acceptable prevalence rates, the strict enforcement of face mask-wearing by security forces raised concerns among many community members and human rights advocates. We recommend more studies on communities9 perspectives on the challenges and benefits of facemask-wearing during the COVID-19 pandemic.
- Feasibility of intranasal delivery of thin-film freeze-dried monoclonal antibodies -
Monoclonal antibodies (mAbs) administered intranasally as dry powders can be potentially applied for the treatment or pre-exposure prevention of viral infections in the upper respiratory tract. However, a method to transform the mAbs from liquid to dry powders suitable for intranasal administration and a device that can spray the dry powders to the desired region of the nasal cavity are needed to fully realize the potentials of the mAbs. Herein, we report that thin-film freeze-drying can be applied to prepare aerosolizable mAb dry powders and that the dry powders can be sprayed into the posterior nasal cavity using the Unidose (UDS) Powder Nasal Spray System from Aptar Pharma. AUG-3387, a human-derived mAb that neutralizes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was used in the present study. First, we prepared AUG-3387 thin-film freeze-dried powders (i.e., TFF AUG-3387 powders) from liquid formulations containing different levels of mAbs. The TFF AUG-3387 powder with the highest solid content (i.e., TFF AUG-3387C powder) was then chosen for further characterization, including the evaluation of the plume geometry, spray pattern, and particle size distribution after the powder was sprayed using the UDS Powder device. Finally, the deposition patterns of the TFF AUG-3387C powder sprayed using the UDS Powder device were studied using 3D-printed nasal replica casts based on an adult model and a child model. It is concluded that it is feasible to intranasally deliver mAbs as dry powders by transforming the mAbs into dry powders using thin-film freeze-drying and then spray the powder using the UDS Powder device.
- SARS-CoV-2 induces acute neurological signs while Calcitonin Gene-Related Peptide (CGRP) signaling blockade reduces interleukin 6 (IL-6) release and weight loss in mouse models -
COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.
- A 50-gene high-risk profile predictive of COVID-19 and Idiopathic Pulmonary Fibrosis mortality originates from a molecular imbalance in monocyte and T-cell subsets that reverses in survivors with post-COVID-19 Interstitial Lung Disease -
Background: We aim to study the source of circulating immune cells expressing a 50-gene signature predictive of COVID-19 and IPF mortality. Methods: Whole blood and Peripheral Blood Mononuclear cells (PBMC) were obtained from 231 subjects with COVID-19, post-COVID-19-ILD, IPF and controls. We measured the 50-gene signature (nCounter, Nanostring), interleukin 6 (IL6), interferon gamma;-induced protein (IP10), secreted phosphoprotein 1 (SPP1) and transforming growth factor beta (TGF-beta) by Luminex. PCR was used to validate COVID-19 endotypes. For single-cell RNA sequencing (scRNA-seq) we used Chromium Controller (10X Genomics). For analysis we used the Scoring Algorithm of Molecular Subphenotypes (SAMS), Cell Ranger, Seurat, Propeller, Kaplan-Meier curves, CoxPH models, Two-way ANOVA, T-test, and Fisher exact. Results: We identified three genomic risk profiles based on the 50-gene signature, and a subset of seven genes, associated with low, intermediate, or high-risk of mortality in COVID-19 with significant differences in IL6, IP10, SPP1 and TGF{beta}-1. scRNA-seq identified Monocytic-Myeloid-Derived Suppressive cells (M-MDSCs) expressing CD14+HLA DRlowCD163+ and high levels of the 7-gene signature (7Gene-M-MDSC) in COVID-19. These cells were not observed in post-COVID-19-ILD or IPF. The 43-gene signature was mostly expressed in CD4 T and CD8 T cell subsets. Increased expression of the 43 gene signature was seen in T cell subsets from survivors with post-COVID-19-ILD. The expression of these genes remained low in IPF. Conclusion: A 50-gene, high-risk profile in COVID-19 is characterized by a genomic imbalance in monocyte and T-cell subsets that reverses in survivors with post-COVID-19 Interstitial Lung Disease.
- Microfluidic antibody profiling after repeated SARS-CoV-2 vaccination links antibody affinity and concentration to impaired immunity and variant escape in patients on anti-CD-20 therapy -
Background: Patients with autoimmune/inflammatory conditions on anti-CD20 therapies, such as Rituximab, have suboptimal humoral responses to vaccination and are vulnerable to poorer clinical outcomes following SARS-CoV-2 infection. We aimed to examine how the fundamental parameters of antibody responses, namely affinity and concentration, shape the quality of humoral immunity after vaccination in these patients. Methods: We performed in depth antibody characterisation in sera collected four to six weeks after each of three vaccine doses to wild-type (WT) SARS-CoV-2 in Rituximab-treated primary vasculitis patients (n=14) using Luminex and pseudovirus neutralisation assays, whereas a novel microfluidic-based immunoassay was used to quantify polyclonal antibody affinity and concentration against both WT and Omicron (B.1.1.529) variants. Comparative antibody profiling was performed at equivalent time points in healthy individuals after three antigenic exposures to WT SARS-CoV-2 (one infection and two vaccinations; n=15) and in convalescent patients after WT SARS-CoV-2 infection (n=30). Results: Rituximab-treated patients had lower antibody levels and neutralisation titres against both WT and Omicron SARS-CoV-2 variants compared to healthy individuals. Neutralisation capacity was weaker against Omicron versus WT both in Rituximab-treated patients and in healthy individuals. In the Rituximab cohort, this was driven by lower antibody affinity against Omicron versus WT (median [range] KD: 21.6 [9.7-38.8] nM vs 4.6 [2.3-44.8] nM, p=0.0004). By contrast, healthy individuals with hybrid immunity produced a broader antibody response, a subset of which recognised Omicron with higher affinity than antibodies in Rituximab-treated patients (median [range] KD: 1.05 [0.45-1.84] nM vs 20.25 [13.2-38.8] nM, p=0.0002), underpinning the stronger serum neutralisation capacity against Omicron in the former group. Rituximab-treated patients had similar anti-WT antibody levels and neutralisation titres to unvaccinated convalescent individuals, despite two more exposures to SARS-CoV-2 antigen. Temporal profiling of the antibody response showed evidence of affinity maturation in healthy convalescent patients after a single SARS-CoV-2 infection which was not observed in Rituximab-treated patients, despite repeated vaccination. Discussion: Our results enrich previous observations of impaired humoral immune responses to SARS-CoV-2 in Rituximab-treated patients and highlight the significance of quantitative assessment of serum antibody affinity and concentration in monitoring anti-viral immunity, viral escape, and the evolution of the humoral response.
- Heterotypic responses against nsp12/nsp13 from prior SARS-CoV-2 infection associates with lower subsequent endemic coronavirus incidence -
Immune responses from prior SARS-CoV-2 infection and COVID-19 vaccination do not prevent re-infections and may not protect against future novel coronaviruses (CoVs). We examined the incidence of and immune differences against human endemic CoVs (eCoV) as a proxy for response against future emerging CoVs. Assessment was among those with known SARS-CoV-2 infection, COVID-19 vaccination but no documented SARS-CoV-2 infection, or neither exposure. Retrospective cohort analyses suggest that prior SARS-CoV-2 infection, but not COVID-19 vaccination alone, protects against subsequent symptomatic eCoV infection. CD8+ T cell responses to the non-structural eCoV proteins, nsp12 and nsp13, were significantly higher in individuals with previous SARS-CoV-2 infection as compared to the other groups. The three groups had similar cellular responses against the eCoV spike and nucleocapsid, and those with prior spike exposure had lower eCoV-directed neutralizing antibodies. Incorporation of non-structural viral antigens in a future pan-CoV vaccine may improve protection against future heterologous CoV infections.
- Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 synergistically enhances antibody evasion and ACE2 binding -
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants like EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. L455F and F456L evade Class 1 NAbs, reducing the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. The perturbed receptor-binding mode leads to the exceptional ACE2 binding and NAb evasion, as revealed by structural analyses. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.
- The impact of spatial connectivity on NPIs effectiveness -
Background. France implemented a combination of non-pharmaceutical interventions (NPIs) to manage the COVID-19 pandemic between September 2020 and June 2021. These included a lockdown in the fall 2020 - the second since the start of the pandemic - to counteract the second wave, followed by a long period of nighttime curfew, and by a third lockdown in the spring 2021 against the Alpha wave. Interventions have so far been evaluated in isolation, neglecting the spatial connectivity between regions through mobility that may impact NPI effectiveness. Methods. Focusing on September 2020 - June 2021, we developed a regionally-based epidemic metapopulation model informed by observed mobility fluxes from daily mobile phone data and fitted the model to regional hospital admissions. The model integrated data on vaccination and variants spread. Scenarios were designed to assess the impact of the Alpha variant, characterized by increased transmissibility and risk of hospitalization, of the vaccination campaign and alternative policy decisions. Results. The spatial model better captured the heterogeneity observed in the regional dynamics, compared to models neglecting inter-regional mobility. The third lockdown was similarly effective to the second lockdown after discounting for immunity, Alpha, and seasonality (51% vs 52% median regional reduction in the reproductive number R0, respectively). The 6pm nighttime curfew with bars and restaurants closed, implemented in January 2021, substantially reduced COVID-19 transmission. It initially led to 49% median regional reduction of R0, decreasing to 43% reduction by March 2021. In absence of vaccination, implemented interventions would have been insufficient against the Alpha wave. Counterfactual scenarios proposing a sequence of lockdowns in a stop-and-go fashion would have reduced hospitalizations and restriction days for low enough thresholds triggering and lifting restrictions. Conclusions. Spatial connectivity induced by mobility impacted the effectiveness of interventions especially in regions with higher mobility rates. Early evening curfew with gastronomy sector closed allowed authorities to delay the third wave. Stop-and-go lockdowns could have substantially lowered both healthcare and societal burdens if implemented early enough, compared to the observed application of lockdown-curfew-lockdown, but likely at the expense of several labor sectors. These findings contribute to characterize the effectiveness of implemented strategies and improve pandemic preparedness. Keywords. COVID-19, NPIs, modeling, curfew, restrictions.
- In vivo affinity maturation of murine B cells reprogrammed to express human antibodies -
CRISPR-edited murine B cells engineered to express human antibody variable chains proliferate, class switch, and secrete these antibodies in vaccinated mice. However, current strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that recombined murine heavy- and kappa-variable genes can be directly and simultaneously overwritten, using Cas12a-mediated cuts at their 3'-most J segments and 5' homology arms complementary to distal V segments. Cells edited in this way to express the HIV-1 broadly neutralizing antibodies 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated recipient mice. 10-1074 variants isolated from these mice bound and neutralized HIV-1 envelope glycoprotein more efficiently than wild-type 10-1074 while maintaining or improving its already low polyreactivity and long in vivo half-life. We further validated this approach by generating substantially broader and more potent variants of the anti-SARS-CoV-2 antibodies ZCB11 and S309. Thus, B cells edited at their native loci affinity mature, facilitating development of broad, potent, and bioavailable antibodies and expanding the potential applications of engineered B cells.
- Assessing nanobody interaction with SARS-CoV-2 Nsp9 -
The interaction between SARS-CoV-2 non-structural protein Nsp9 and the nanobody 2NSP90 was investigated by NMR spectroscopy using the paramagnetic perturbation methodology PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation). The Nsp9 monomer is an essential component of the replication and transcription complex (RTC) that reproduces the viral gRNA for subsequent propagation. Therefore preventing Nsp9 recruitment in RTC would represent an efficient antiviral strategy that could be applied to different coronaviruses, given the Nsp9 relative invariance. The NMR results were consistent with a previous characterization suggesting a 4:4 Nsp9-to-nanobody stoichiometry with the occurrence of two epitope pairs on each of the Nsp9 units that establish the inter-dimer contacts of Nsp9 tetramer. The oligomerization state of Nsp9 was also analyzed by molecular dynamics simulations and both dimers and tetramers resulted plausible. However a different distribution of the mapped epitopes on the tetramer surface with respect to the former 4:4 complex could also be possible, as well as different stoichiometries of the Nsp9-nanobody assemblies such as the 2:2 stoichiometry suggested by the recent crystal structure of the Nsp9 complex with 2NSP23 (PDB ID: 8dqu), a nanobody exhibiting essentially the same affinity as 2NSP90. The experimental NMR evidence, however, ruled out the occurrence in liquid state of the relevant Nsp9 conformational change observed in the same crystal structure.
- Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages -
Motivation: Charged amino acid residues on the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to influence its binding to different cell surface receptors, its non-specific electrostatic interactions with the environment, and its structural stability and conformation. It is therefore important to obtain a good understanding of amino acid mutations that affect the total charge on the spike protein which have arisen across different SARS-CoV-2 lineages during the course of the virus' evolution. Results: We analyse the change in the number of ionizable amino acids and the corresponding total charge on the spike proteins of almost 2000 SARS-CoV-2 lineages that have emerged over the span of the pandemic. Our results show that the previously observed trend toward an increase in the positive charge on the spike protein of SARS-CoV-2 variants of concern has essentially stopped with the emergence of the early omicron variants. Furthermore, recently emerged lineages show a greater diversity in terms of their composition of ionizable amino acids. We also demonstrate that the patterns of change in the number of ionizable amino acids on the spike protein are characteristic of related lineages within the broader clade division of the SARS-CoV-2 phylogenetic tree. Due to the ubiquity of electrostatic interactions in the biological environment, our findings are relevant for a broad range of studies dealing with the structural stability of SARS-CoV-2 and its interactions with the environment. Availability: The data underlying the article are available in the online Supplementary Material.
- Screening Peptide Drug Candidates to Neutralize Whole Viral Agents : A Case study with SARS-CoV-2 Virus -
Covid19 pandemic revealed the reality for the need of therapeutic and pharmaceutical molecule development in a short time with different approaches. Although the enhancement of immunological memory by vaccination was the quicker and robust strategy, still medication is required for immediate treatment for a patient. For this purpose, one of the approaches is developing new therapeutic molecule development like peptide-based drugs. Also, peptides can be used developing other molecules like nanobodies. Here, M13 phage display library was used for selecting SARS-CoV-2 interacting peptides for developing a neutralizing molecule for further use. Biopanning was applied with four iterative cycles to select phages displaying different 12-amino acid-long peptides. Then, the M13 phage genomic region where peptide sequences expressed were analyzed and sequences were obtained. Randomly selected peptide sequences were synthesized by solid-state peptide synthesis method. These peptides were analyzed by quartz crystal microbalance method in terms or peptide interaction capacity with specifically wild-type S protein. Next, QCM data was further validated by enzyme-linked immunosorbent assay (ELISA) in order to check peptides according to their neutralizing capacity rather than binding to S1 protein. The results showed that, phage display served an opportunity for selecting peptides which can be used and developed further as pharmaceutical molecules. More specifically, scpep3, scpep8 and scpep10 had both binding and neutralizing capacity for S1 protein as a candidate for therapeutic molecule.
- A bioactive peptide from the pearl has dual roles in resisting SARS-CoV-2 infection and its complications -
Angiotensin-converting enzyme 2 (ACE2) is a critical receptor for the entry of the SARS-CoV-2 virus into cells. Moreover, a decrease in ACE2 level and its activity due to SARS-CoV-2 infection is considered a crucial reason for the development of Covid-19-associated complications. Here, we report a bioactive peptide derived from the seawater pearl oyster Pinctada fucata, named SCOL polypeptide, which binds strongly to ACE2 and effectively inhibits 65% of the binding of the SARS-CoV-2 S protein to ACE2; thus, this peptide can be used as a blocker to enable cells to resist SARS-CoV-2 infection. The SCOL polypeptide also increases ACE2 enzyme activity by 3.76 times. Previous studies have shown that ACE2 deficiency is associated with inflammation, pain, cardiovascular diseases, insulin resistance, and nervous system injury. Therefore, the SCOL polypeptide can be used to treat or alleviate complications such as lung inflammation, pain, diabetes, cardiovascular diseases, and loss of taste or smell caused by SARS-CoV-2 infection. Thus, the SCOL polypeptide can play a dual role in resisting SARS-CoV-2 infection.
Evaluation of Concordance Between Exhaled Air Test (eBAM-CoV) and RT-PCR to Detect SARS-CoV-2 - Conditions: SARS-CoV-2 Infection; COVID-19; Coronavirus
Interventions: Device: eBAM Cov Testing
Sponsors: Centre Hospitalier Universitaire de Nīmes; University of Nimes; brains’ laboratory sas, FRANCE
Not yet recruiting
A Phase I/IIa Study to Safety, Tolerability and Immunogenicity of EG-COVII in Healthy Adult - Conditions: COVID-19
Interventions: Biological: EG-COVII
Sponsors: EyeGene Inc.
Recruiting
Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers - Conditions: Viral Infection COVID-19
Interventions: Drug: Aterixen
Sponsors: Valenta Pharm JSC
Not yet recruiting
Long COVID Brain Fog: Cognitive Rehabilitation Trial - Conditions: Long COVID; Brain Fog; Cognitive Impairment; Cognitive Dysfunction; Post-Acute COVID-19 Syndrome
Interventions: Behavioral: Speed of Processing Training; Behavioral: In-lab Instrumental Activities of Daily Living Training; Behavioral: In-lab Brain Health Training; Behavioral: Transfer Package; Behavioral: Follow Up Phone Calls; Behavioral: Vocational Rehabilitation; Behavioral: Peer Mentoring
Sponsors: University of Alabama at Birmingham; National Institute on Disability, Independent Living, and Rehabilitation Research
Not yet recruiting
A Practical RCT of TCM in the Treatment of LCOVID and Analysis of Syndrome Types and Medication Characteristics. - Conditions: Long COVID
Interventions: Drug: Traditional Chinese medicine treatment; Drug: Western medicine treatment
Sponsors: Chinese University of Hong Kong
Not yet recruiting
Paradoxical Response to Chest Wall Loading in Mechanically Ventilated Patients - Conditions: ARDS; COVID-19; Mechanical Ventilation Pressure High; Ventilator-Induced Lung Injury
Interventions: Diagnostic Test: Manual loading of the chest wall
Sponsors: HealthPartners Institute
Withdrawn
Narrative Intervention for Long COVID-19 (NICO) - Conditions: Long COVID; Long Covid19
Interventions: Behavioral: Narrative Intervention for Long COVID-19 (NICO)
Sponsors: University of Colorado, Denver
Active, not recruiting
Inspiratory Muscle Training in People With Long COVID-19- A Pilot Investigation. - Conditions: Long COVID
Interventions: Device: PrO2
Sponsors: University of Bath; Swansea University
Not yet recruiting
Inspiratory Muscle Strength Training in Post-Covid Syndrome - Conditions: Cardiovascular Abnormalities; Post-COVID-19 Syndrome; Physical Exercise
Interventions: Other: Inspiratory muscle strength training
Sponsors: D’Or Institute for Research and Education
Recruiting
Immunogenicity of Concomitant Administration of COVID-19 Vaccines With Influenza Vaccines - Conditions: COVID-19; Influenza; Vaccine Reaction; Contaminant Injected
Interventions: Biological: Omicron-containing COVID-19 vaccine; Biological: influenza vaccine
Sponsors: Catholic Kwandong University; Korea University Guro Hospital
Recruiting
Home-Based Respiratory Muscle Strength Training Program for Individuals With Post-COVID-19 Persistent Dyspnea - Conditions: Post-COVID-19 Syndrome; Dyspnea
Interventions: Device: Respiratory Muscle Strength Trainers
Sponsors: University of South Florida
Not yet recruiting
Rural Tailored Communication to Promote SARS-CoV-2 Antibody Testing in Saliva - Conditions: SARS-CoV2 Infection
Interventions: Behavioral: General SARS-CoV-2 Communication; Behavioral: Rural-Targeted SARS-CoV-2 Communication
Sponsors: Michigan State University; National Cancer Institute (NCI); Johns Hopkins University
Recruiting
Cognitive Rehabilitation Therapy for COVID-19 - Conditions: Post-Acute COVID-19 Syndrome
Interventions: Behavioral: Compensatory Cognitive Training for COVID-19; Behavioral: Holistic Cognitive Education
Sponsors: VA Office of Research and Development
Not yet recruiting
COVID Rehabilitation - Conditions: Rehabilitation; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders
Interventions: Behavioral: One day course; Behavioral: Individual follow-ups
Sponsors: University Hospital of North Norway; University of Bergen; Oslo University Hospital; Norwegian University of Science and Technology
Not yet recruiting
Phase 3 Open-Label Controlled Trial of Convalescent Plasma in Early COVID-19 Infection - Conditions: Covid19
Interventions: Drug: Convalescent Plasma; Other: Standard of Care
Sponsors: Larkin Community Hospital
Withdrawn
The effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats treated with the ACE2 inhibitor MLN-4760 - CONCLUSIONS: Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H(2)S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2…
Assessing the gene expression of the adenosine 5’-monophosphate-activated protein kinase (AMPK) and its relation with the IL-6 and IL-10 plasma levels in COVID-19 patients - CONCLUSION: Increasing AMPK gene expression is likely a necessary effort of the immune system to inhibit inflammation in critical COVID-19. However, this effort seems to be inadequate, probably due to factors that induce inflammation, like erythrocyte sedimentation rate (ESR) and IL-6.
SARS-CoV-2 neurotropism-induced anxiety and depression-like behaviors require Microglia activation - The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with a wide range of “long COVID” neurological symptoms. However, the mechanisms governing SARS-CoV-2 neurotropism and its effects on long-term behavioral changes remain poorly understood. Using a highly virulent mouse-adapted SARS-CoV-2 strain, denoted as SARS2-N501Y (MA30) , we demonstrated that intranasal inoculation of SARS2-N501Y (MA30) results in…
Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing - BACKGROUND: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false-negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive…
Intestinal injury and vasculitis biomarkers in cats with feline enteric coronavirus and effusive feline infectious peritonitis - OBJECTIVE: To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection.
ORF3c is expressed in SARS-CoV-2-infected cells and inhibits innate sensing by targeting MAVS - Most SARS-CoV-2 proteins are translated from subgenomic RNAs (sgRNAs). While the majority of these sgRNAs are monocistronic, some viral mRNAs encode more than one protein. One example is the ORF3a sgRNA that also encodes ORF3c, an enigmatic 41-amino-acid peptide. Here, we show that ORF3c is expressed in SARS-CoV-2-infected cells and suppresses RIG-I- and MDA5-mediated IFN-β induction. ORF3c interacts with the signaling adaptor MAVS, induces its C-terminal cleavage, and inhibits the interaction…
Chemical Characteristics and Biological Activity Screening of Pistacia lentiscus Mastic Gum and Leaves from Turkiye - CONCLUSION: The mastic gum and leaves obtained from P. lentiscus may have great potential in terms of their chemical content, antiviral and cytotoxic activities. In ovo antiviral activity studies on the P. lentiscus were evaluated for the first time. Attributable to these properties, it is a sustainable, renewable natural resource that can be used as an additive and flavor in the food and pharmaceutical industries. This article is protected by copyright. All rights reserved.
Evaluation of Potential Peptide-Based Inhibitors against SARS-CoV-2 and Variants of Concern - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has greatly affected all aspect of life. Although several vaccines and pharmaceuticals have been developed against SARS-CoV-2, the emergence of mutated variants has raised several concerns. The angiotensin-converting enzyme (ACE2) receptor cell entry mechanism of this virus has not changed despite the vast mutation in emerging variants. Inhibiting the spike protein by which the virus identifies the host ACE2 receptor is a…
Some novel bioactivities of Virgibacillus halodenitrificans carotenoids, isolated from Wadi El-Natrun lakes - Carotenoids come in second among the most frequent natural pigments and are utilized in medications, nutraceuticals, cosmetics, food pigments, and feed supplements. Based on recent complementary work, Virgibacillus was announced for the first time as a member of Wadi El-Natrun salt and soda lakes microbiota, identified as Virgibacillus halodenitrificans, and named V. halodenitrificans DASH; hence, this work aimed to investigate several in vitro medicinal bioactivities of V. halodenitrificans…
Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome - INTRODUCTION: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main…
A Naïve Phage Display Library-Derived Nanobody Neutralizes SARS-CoV-2 and Three Variants of Concern - CONCLUSION: Our study highlights a novel nanobody, Nb-H6, that may be useful therapeutically in SARS-CoV-2 and VOC outbreaks and pandemics. These findings also provide a molecular foundation for further studies into how nanobodies neutralize SARS-CoV-2 and variants and imply potential therapeutic targets for the treatment of COVID-19.
Macromolecules: Synthesis, antimicrobial, POM analysis and computational approaches of some glucoside derivatives bearing acyl moieties - Macromolecules i.e., carbohydrate derivatives are crucial to biochemical and medical research. Herein, we designed and synthesized eight methyl α-D-glucopyranoside (MGP) derivatives (2-8) in good yields following the regioselective direct acylation method. The structural configurations of the synthesized MGP derivatives were analyzed and verified using multiple physicochemical and spectroscopic techniques. Antimicrobial experiments revealed that almost all derivatives demonstrated noticeable…
Synthesis, structural characterization, antioxidant, cytotoxic activities and docking studies of schiff base Cu(II) complexes - By combining hydrazide with 2-Acetylpyridine, a hydrazone ligand (HL) was successfully created. Several copper (II) salts have been used to create three copper (II) hydrazone complexes (acetate, sulphate, and chloride). The hydrazide ligand and its copper (II) complexes (1-3) were studied via variety of analytical techniques, including elemental analysis, electronic, infrared, UV-vis Spectrum, XRD study, thermal analysis, also molar conductivity amounts. The spectrum results indicate that in all…
Pyrazolidinone-Based Peptidomimetic SARS-CoV-2 Mpro inhibitors - The main protease (M^(pro)) of SARS-CoV-2 is an attractive drug target for COVID-19 treatment as it plays an integral role in the proliferation of coronavirus. Herein, we describe the investigation of β- and γ-lactams as electrophilic “warheads” for covalent binding to Cys145 of the M^(pro) active site. The highest inhibitory activity (IC(50) = 45 ± 3 μM) was achieved using a pyrazolidinone warhead attached to the targeting dipeptide. Importantly, the synergy of the warhead and the targeting…
In vitro testing of host-targeting small molecule antiviral matriptase/TMPRSS2 inhibitors in 2D and 3D cell-based assays - The outbreak of coronavirus disease 2019 (COVID-19) pandemic strongly stimulated the development of small molecule antivirals selectively targeting type II transmembrane serine proteases (TTSP), required for the host-cell entry of numerous viruses. A set of 3-amidinophenylalanine derivatives (MI-21, MI-472, MI-477, MI-485, MI-1903 and MI-1904), which inhibit the cleavage of certain viral glycoproteins was characterized in 2D and 3D primary human hepatocyte models on collagen- and…