- Daily Dynamics of Parental Mental Health: Investigating Depressive Symptoms and Negative Parental Experiences -
Background: Investigating psychopathological processes and how these are connected to psychiatric symptoms is important to understand how disorder states emerge and are maintained over time. Focusing on within-person relationships between variables further allows investigation of how these relations on average unfold within individuals. Methods: This preregistered intensive longitudinal study investigates connections between depressive symptoms, psychopathological processes, and negative parental experiences. Daily observations from 1036 parents were retrieved from two 40-day periods during the COVID-19 pandemic. The data was modelled using multilevel dynamic network analysis, unveiling across-day associations and contemporaneous interactions within the same time window. Results: On an across-day basis, helplessness was strongly interwoven with and predictive of the cognitive-affective features of depression and the other psychopathological processes. Being overwhelmed by the parental role (parenting stress) and emotionally drained as a parent (parental burnout) reciprocally reinforced each other from one day to the next, indicating how these components can manifest as a vicious loop over time. Finally, depressive symptomatology and negative parental experiences displayed within-day connections, with emotion regulation difficulties being connected to all parental components. Conclusions: The findings suggest that vicious cycles between helplessness and worthlessness predict the prolonged experience of depressed states in parents and that elevations in parenting stress and parental burnout reinforce each other over time.
- Generalized trust rather than perception of relational mobility correlates with nominating close friends in a social network -
A social environment, such as relational mobility, which represents the availability of opportunities to develop new relationships in society, cultivates an individual’s psychology and social network. Generalized trust, which represents trust among people in general, is a tendency to expand individuals’ social ties in a fluid society. Using the data of 170 students, we analyzed whether an individual’s belief of generalized trust and perception of relational mobility are related to the social network. We conducted a survey to assess psychological measures and social networks under the COVID-19 pandemic for first-year university students. The analyses revealed that generalized trust was significantly associated with the presence of outdegrees (i.e., the nomination of close friends) and the absence of indegrees (i.e., being nominated by others). In contrast, perception of relational mobility was not significantly associated with generalized trust and any social network measures. Behavioral trust, measured using a Trust Game approximately six months later, was not significantly associated with network characteristics. The results support the argument that the belief of generalized trust functions as a psychological mechanism to expand individuals’ relationships in their social networks.
- Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses -
The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the in vivo nasal epithelium, to compare lethal (SARS-CoV-2 and MERS-CoV) and seasonal (HCoV-NL63 and HCoV-229E) HCoVs. All four HCoVs replicate productively in nasal cultures but diverge significantly in terms of cytotoxicity induced following infection, as the seasonal HCoVs as well as SARS-CoV-2 cause cellular cytotoxicity as well as epithelial barrier disruption, while MERS-CoV does not. Treatment of nasal cultures with type 2 cytokine IL-13 to mimic asthmatic airways differentially impacts HCoV replication, enhancing MERS-CoV replication but reducing that of SARS-CoV-2 and HCoV-NL63. This study highlights diversity among HCoVs during infection of the nasal epithelium, which is likely to influence downstream infection outcomes such as disease severity and transmissibility.
- Deep learning-based Drug discovery of Mac domain of SARS-CoV-2 (WT) Spike inhibitors: using experimental ACE2 Inhibition TR-FRET Assay Screening and Molecular Dynamic Simulations. -
SARS-CoV-2 exploits the homotrimer transmembrane Spike glycoproteins (S protein) during host cell invasion. Omicron, delta, and prototype SARS-CoV-2 receptor-binding domain show similar binding strength to hACE2 (Angiotensin-Converting Enzyme 2). Here we utilized multi-ligand virtual screening to identify small molecule inhibitors for their efficacy against SARS-CoV-2 virus using quantum Docking, pseudovirus ACE2 Inhibition TR-FRET Assay Screening, and Molecular Dynamic simulations (MDS). 350-thousand compounds were screened against the macrodomain of non-structural protein 3 of SARS-CoV-2. Using TR-FRET Assay, we filtered out two of 10 compounds that had no reported activity in in-vitro screen against Spike S1: ACE2 binding assay. Percentage Inhibition at 30 micromolar was found to be 79% for Compound F1877-0839 and 69% for Compound F0470-0003. This first of its kind study identified FILLY pocket in macrodomains. Our 200 ns MDS revealed stable binding poses of both leads. They can be used for further development of preclinical candidates.
- SARS-CoV-2 vaccine and increased myocarditis mortality risk: A population based comparative study in Japan -
ABSTRACT Objective: To investigate the association between SARS-CoV-2 vaccination and myocarditis death Design: Population based comparative mortality study Setting: Japan Participants: Vaccinated population was 99 834 543 individuals aged 12 years and older who have been received SARS-CoV-2 vaccine once or twice by 14 February 2022. Reference population was defined persons aged 10 years and older from 2017 to 2019. Main outcome measures: The primary outcome was myocarditis death, defined as the case with “myocarditis” for cause of death and with onset 28 days or less after vaccination disclosed on 5 August 2022. Myocarditis mortality rate ratio (MMRR) of the SARS-CoV-2 vaccinated to the reference population by 10-year age group and standardised mortality ratio (SMR) were calculated. Mortality odds ratios (MORs) by 10-year age group were also calculated for supplementary analysis. Healthy vaccine effect-adjusted MMRRs (adMMRRs) or adjusted SMR (adSMR) were calculated by dividing MMRRs or SMR by 0.24 respectively. Results: Number of myocarditis death which met the inclusion criteria were 38 cases. MMRR (95% confidence interval) was 4.03 (0.77 to 13.60) in 20s, 6.69 (2.24 to 16.71) in 30s, 3.89 (1.48 to 8.64) in 40s, respectively. SMR of myocarditis was 2.01 (1.44 to 2.80) for overall vaccinated population, 1.65 (1.07 to 2.55) for those 60 years or older. Estimated adMMRRs and adSMR were about 4 times higher than the MMRRs and SMR. Pooled MOR for myocarditis were 205.60 (133.52 to 311.94). Conclusion: SARS-CoV-2 vaccination was associated with higher risk of myocarditis death, not only in young adults but also in all age groups including the elderly. Considering healthy vaccinee effect, the risk may be 4 times or higher than the apparent risk of myocarditis death. Underreporting should also be considered. Based on this study, risk of myocarditis following SARS-CoV-2 vaccination may be more serious than that reported previously.
- N6-Adenosine Methylation of SARS-CoV-2 5-UTR Regulates Translation -
The coronavirus disease 2019 (COVID19) continues to spread despite global vaccination efforts. This, alongside the rapid emergence of vaccine resistant variants, creates a need for orthogonal therapeutic strategies targeting more conserved facets of severe acute respiratory syndrome coronavirus (SARS-CoV-2). One conserved feature of all coronaviruses is their ability to undergo discontinuous transcription wherein individual open reading frames fuse with the 5-UTR leader sequence during negative-strand RNA synthesis. As such all viral protein coding genes use the same 5-UTR for translation. Using in vitro reporter assays, we demonstrate that the SARS-CoV-2 5-UTR efficiently initiates protein translation despite its predicted structural complexity. Through a combination of bioinformatic and biochemical assays, we demonstrate that a single METTL3-dependent m6A methylation event in SARS-CoV-2 5-UTR regulates the rate of translation initiation. We show that m6A likely exerts this effect by destabilizing secondary structure in the 5-UTR, thereby facilitating access to the ribosomal pre-initiation complex. This discovery opens new avenues for novel therapeutic strategies aimed at controlling the ability of SARS-CoV-2 to replicate in host cells.
- Measuring Intolerance of Uncertainty after Acquired Brain Injury. Part 1: The Factor Structure of the Intolerance of Uncertainty Scale-12 -
Intolerance of uncertainty (IU) is a risk factor for poor mental health. Acquired brain injury (ABI), such as stroke or traumatic brain injury, often brings considerable uncertainty. This is the first of a two-part investigation of the psychometric properties of the Intolerance of Uncertainty Scale-12 (IUS-12) in ABI. Here, we evaluate its internal consistency and factor structure in 176 adults with ABI. A two-factor structure (Prospective Anxiety and Inhibitory Anxiety) was superior to a one-factor model. However, some fit statistics were unacceptable. In an exploratory factor analysis, a new two-factor model emerged with a superior fit. A bifactor model provided even better fit, though the sample size precluded exhaustive evaluation. For now, retaining the original Prospective Anxiety and Inhibitory Anxiety subscales is recommended for ABI. IUS-12 scores did not differ pre- or during COVID-19 assessment, suggesting the IUS-12 is measuring individual differences regardless of uncertainty levels.
- Rethinking Remdesivir for COVID-19: A Bayesian Reanalysis of Trial Findings -
Background: Following testing in clinical trials, the use of remdesivir for treatment of COVID-19 has been authorized for use in parts of the world, including the USA and Europe. Early authorizations were largely based on results from two clinical trials. A third study published by Wang et al. was underpowered and deemed inconclusive. Although regulators have shown an interest in interpreting the Wang et al. study, under a frequentist framework it is difficult to determine if the non-significant finding was caused by a lack of power or by the absence of an effect. Bayesian hypothesis testing does allow for quantification of evidence in favor of the absence of an effect. Findings: Results of our Bayesian reanalysis of the three trials show ambiguous evidence for the primary outcome of clinical improvement and moderate evidence against the secondary outcome of decreased mortality rate. Additional analyses of three studies published after initial marketing approval support these findings. Conclusions: We recommend that regulatory bodies take all available evidence into account for endorsement decisions. A Bayesian approach can be beneficial, in particular in case of statistically non-significant results. This is especially pressing when limited clinical efficacy data is available.
- STRA6: key to inflammatory pathways in COVID-19 -
The COVID-19 pandemic, caused by SARS-CoV-2, has infected more than 260 million people worldwide, causing more than 5.2 million deaths. Unlike other viral infections, COVID-19 is characterized by widespread and severe systemic effects, immune dysregulation, pneumonia, ARDS, and multiple organ damage. It also causes serious inflammatory, autoimmune, endocrine, and neuropsychiatric diseases also called post-COVID syndromes. This broad spectrum of disease seen in COVID-19 cannot be explained by the previously described mechanism of viral tropism based on a single receptor mediated by ACE2 and TMPRSS2 receptors. The pathogenesis of COVID-19 can only be explained by the influence of many receptors and signaling pathways. At a crossroads in retinol metabolism and multiple inflammation-related cellular signaling pathways, STRA6 plays a key role in the pathogenesis of COVID-19. Systemic organ involvement, neuroendocrine involvement, and immunological involvement in COVID-19 can be explained very clearly through STRA6 signaling. Retinoid metabolism and STRA6 activity interact. It has been previously shown that retinol levels are reduced in COVID-19. Due to retinol depletion in COVID-19, the functions of STRA6 are also impaired. This leads to the disruption of multiple cellular signaling pathways associated with inflammation. STRA6 has a key role in the regulation of inflammatory pathways and retinoid signaling in the pathogenesis of COVID-19 and is at the center of the inflammatory process in COVID-19 due to the multiple cellular signaling pathways it directs. Targeting STRA6 and its associated signaling pathways may yield result in the prevention and treatment of many inflammatory diseases as well as COVID-19.
- Four points regarding reproducibility and external statistical validity: a comment on Walter et al. -
Walter et al. (2021) present phase 1–2–3 trial data that show two doses of the BNT162b2 (Pfizer–BioN-Tech) Covid-19 vaccine were safe and effective in children aged 5–11 years. Given that millions of children in this age group are receiving the paediatric Pfizer COVID-19 vaccine, that there are potential risks, and that the balance of benefits over potential risks is more limited in children compared to adults due to low rates of serious disease (ATAGI 2021), gold standards ought to be applied to supporting data in terms of placebo-controlled disease endpoint efficacy trials, safety databases large enough to detect adverse events, and appropriate data sharing to enable reproduction and scrutiny of results. Four points are worthy of attention regarding the reproducibility and external statistical validity of the analysis reported in Walter et al. (2021). ‘External validity’ refers to the extent to which conclusions drawn from the data (and statistical tests thereof) are likely to correspond to, or be generalisable to, the real world (Campbell 1957). ‘Reproducibility’ refers to the ability of independent researchers to draw the same conclusions from the data (Kass et al. 2016).
- Investigating the role of binding free energy, binding affinity and antibody escape in the evolution of SARS-CoV-2 spike protein. -
SARS-CoV-2 is considered a pandemic virus and presents a major strain on public health globally. SARS-CoV-2 infects mammalian cells by binding to its receptor, ACE2 which is mediated by the viral spike glycoprotein, specifically the receptor binding domain (RBD) within the spike protein. Recent development of vaccines against SARS-CoV-2 spike protein are currently the best strategy to reduce morbidity and mortality from infection. Like all viruses, SARS-CoV-2 evolves which may result in mutations which are benign or alter its viral fitness. The evolution of SARS-CoV-2 may increase the virulence, possibly by increasing the infectivity of the virus through strengthening the binding of the RBD to ACE2 or enabling the virus to evade naturally or vaccine induced immune responses. To address the need to characterise the evolution of SARS-CoV-2, this study has compared SARS-CoV-2 sequences globally to the Wuhan reference strain at different time points. Additionally, by assigning scores to sequence data, which quantify each sequences binding strength to ACE2 and ability to evade patient derived antibodies, we have demonstrated that over time SARS-CoV-2 has evolved in less than one year to increase its ability to evade antibodies and increase the binding free energy between the RBD and ACE2.
- Host independent deletion hotspots in the SARS-CoV-2 genome -
SARS-CoV-2 infects a wide range of hosts in varying degrees. The RNA genome of SARS-CoV-2 makes it prone to mutations. Advantageous mutations help the virus to evolve and the virus maintains such mutations across species. Here in this study, all non-human hosts-derived SARS-CoV-2 genomic sequences from the GISAID database were analyzed, and identified several deletion hotspots, which are maintained by the virus, across various host species, indicating their important role in the virus evolution. Several of these deletion hotspots are also found in human-derived SARS-CoV-2 genomic sequences. These deletion hotspots have the potential to affect the pathogenicity and virulence of the virus and have a role in molecular and serological diagnostics. Potentially, they can lead to immune escape, resulting in vaccine failure and drug-resistant variants.
- Diet Induced Obesity and Diabetes Enhance Mortality and Reduces Vaccine Efficacy for SARS-CoV-2 -
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, in December 2019. As of October 2022, there have been over 625 million confirmed cases of COVID-19, including over 6.5 million deaths. Epidemiological studies have indicated that comorbidities of obesity and diabetes mellitus are associated with increased morbidity and mortality following SARS-CoV-2 infection. We determined how the comorbidities of obesity and diabetes affect morbidity and mortality following SARS-CoV-2 infection in unvaccinated and adjuvanted spike nanoparticle (NVX-CoV2373) vaccinated mice. We find that obese/diabetic mice infected with SARS-CoV-2 have increased morbidity and mortality compared to age matched normal mice. Mice fed a high-fat diet (HFD) then vaccinated with NVX-CoV2373 produce equivalent neutralizing antibody titers to those fed a normal diet (ND). However, the HFD mice have reduced viral clearance early in infection. Analysis of the inflammatory immune response in HFD mice demonstrates a recruitment of neutrophils that was correlated with increased mortality and reduced clearance of the virus. This model recapitulates the increased disease severity associated with obesity and diabetes in humans with COVID-19 and is an important comorbidity to study with increasing obesity and diabetes across the world.
- The impact of the ABO/Rh blood group on susceptibility and severity among COVID-19 patients in Luanda, Angola -
SARS-CoV-2 is a public health concern worldwide. Identification of biological factors that could influence transmission and worsen the disease has been the subject of extensive investigation. Herein, we investigate the impact of the ABO/Rh blood group on susceptibility and severity among COVID-19 patients in Luanda, Angola. This was a multicentric cohort study conducted with 101 COVID-19 patients. Chi-square and logistic regression were calculated to check factors related to the worsening of the disease and deemed significant when p<0.05. Blood type O (51.5%) and Rh-positive (93.1%) were the most frequent. Patients from blood type O had a high risk to severe disease [OR: 1.33 (95% CI: 0.42 - 4.18), p=0.630] and hospitalization [OR: 2.59 (95% CI: 0.84 - 8.00), p=0.099]. Also, Rh-positive blood type presented a high risk for severe disease (OR: 10.6, p=0.007) and hospitalization (OR: 6.04, p=0.026). We find a high susceptibility, severity, hospitalization, and mortality, respectively, among blood group O and Rh-positive patients, while blood group AB presented a low susceptibility, severity, hospitalization, and mortality, respectively. Our findings add to the body of evidence suggesting that ABO/Rh blood groups play an important role in the course of SARS-CoV-2 infection.
- COVID-19 outbreaks in child care facilities Alberta from March 2020 to December 31, 2021 -
Background: Children attending child care are vulnerable to SARS CoV-2 infection, and mitigation measures like masking, distancing, enhanced hygiene are not feasible for this population. Describing outbreak growth during the COVID-19 pandemic in child care centres may provide insight in how to best mitigate the risks of COVID-19 and other infectious diseases in these settings. Objective: To describe the characteristics of child care outbreaks and associated cases in Alberta. Methods: Our observational study used data on outbreaks and associated cases tracked through the Alberta Health Services Communicable Disease Outbreak Management database. We included all COVID-19 outbreaks opened in child care facilities in the province (March 2020 to December 31, 2021). We compared the characteristics of outbreaks and cases during each wave of the pandemic. Outcome: 841 outbreaks were opened in Alberta, including 4613 cases (70.2% in children and 29.8% adults). Outbreaks averaged 5.5 cases per outbreak, and the average duration of time between symptoms starting in the first and last case was 9.7 days. The likely index was a child in 55.1% of outbreaks. Conclusions: Adults are a high proportion of cases compared to their proportion of the population at child care facilities, and have consistently higher attack rates than children. Children have the highest attack rates when other children are the index case. Measures shown to be effective in other settings to reduce spread among adults can be implemented here, such as vaccination, strictly enforcing exclusion of those symptomatic, and facilitating rapid testing.
A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir - Condition: COVID-19
Interventions: Drug: nirmatrelvir; Drug: ritonavir; Drug: placebo for nirmatrelvir
Sponsor: Pfizer
Not yet recruiting
Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell) - Condition: COVID-19
Interventions: Biological: Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell); Biological: Inactivated COVID-19 vaccine (Vero Cell)
Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; First Affiliated Hospital Bengbu Medical College
Active, not recruiting
A Phase III Study to Evaluate Immunogenicity and Safety of COVID-19 Vaccine EuCorVac-19 in Healthy Adults - Condition: COVID-19
Interventions: Biological: EuCorVac-19; Biological: ChAdOx1
Sponsor: EuBiologics Co.,Ltd
Recruiting
COVID-19 Testing and Vaccine Literacy for Women With Criminal Legal System Involvement - Condition: COVID-19 Pandemic
Intervention: Behavioral: Tri-City COVID Attitudes Study
Sponsor: University of Kansas Medical Center
Recruiting
JT001 (VV116) for the Treatment of COVID-19 - Condition: Mild to Moderate COVID-19
Interventions: Drug: JT001; Drug: Placebo
Sponsors: Shanghai Vinnerna Biosciences Co., Ltd.; Sponsor GmbH
Not yet recruiting
Boost Intentions and Facilitate Action to Promote Covid-19 Booster Take-up - Conditions: COVID-19; Vaccines
Interventions: Behavioral: Eligibility reminder; Behavioral: Link to a narrow set of vaccine venues; Behavioral: Link to a broad set of vaccine venues; Behavioral: Doctors’ recommendation and value of vaccine
Sponsor: University of California, Los Angeles
Not yet recruiting
Effects of Prompt to Bundle Covid-19 Booster and Flu Shot - Conditions: COVID-19; Vaccines
Interventions: Behavioral: Reminder to boost protection against COVID-19; Behavioral: Flu Tag Along; Behavioral: COVID-19 Booster & Flu Bundle
Sponsor: University of California, Los Angeles
Not yet recruiting
Information Provision and Consistency Framing to Increase COVID-19 Booster Uptake - Conditions: COVID-19; Vaccines
Interventions: Behavioral: Reminder that facilitates action; Behavioral: Consistency framing; Behavioral: Information provision about the uniqueness of the bivalent booster; Behavioral: Information provision about bivalent booster eligibility; Behavioral: Information provision about the severity of COVID-19 symptoms
Sponsor: University of California, Los Angeles
Not yet recruiting
VAX-MOM COVID-19: Increasing Maternal COVID-19 Vaccination - Conditions: Immunization; Infection; Pregnancy Related; COVID-19
Interventions: Behavioral: VAX-MOM COVID-19 Intervention; Other: Standard of Care
Sponsors: University of Rochester; Centers for Disease Control and Prevention; University of California, Los Angeles
Not yet recruiting
Respiratory Muscles After Inspiratory Muscle Training After COVID-19 - Conditions: COVID-19; Diaphragm Injury
Intervention: Device: Inspiratory Muscle Training (IMT)
Sponsors: RWTH Aachen University; Philipps University Marburg Medical Center
Recruiting
COVID-19 Simulation Education on Nursing Students - Conditions: COVID-19 Pandemic; Simulation of Physical Illness
Interventions: Behavioral: Simulation training; Other: Control Group
Sponsor: Mehmet Akif Ersoy University
Completed
COVID-19 Booster Dose Reminder/Recall for Adolescents - Condition: COVID-19 Vaccines
Intervention: Behavioral: Reminder/Recall Sent Via Preferred Method of Communication
Sponsor: Marshfield Clinic Research Foundation
Active, not recruiting
COVID-19 MP Biomedicals SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions: SARS-CoV2 Infection; COVID-19
Interventions: Device: iCura COVID-19 Antigen Rapid Home Test; Device: RT-PCR Test
Sponsors: MP Biomedicals, LLC; EDP Biotech
Completed
COVID-19 MP Biomedicals Rapid SARS-CoV-2 Antigen Test Usability - Conditions: Sars-CoV-2 Infection; COVID-19
Intervention: Device: Rapid SARS-CoV-2 Antigen Test
Sponsors: MP Biomedicals, LLC; EDP Biotech
Completed
A Preliminary Exploratory Study to Evaluate the Safety and Immunogenicity of Omicron Variant Bivalent Vaccine V-01-B5 - Condition: COVID-19 Pandemic
Interventions: Biological: V-01/V-01-B5; Biological: V-01-351/V-01-B5; Biological: V-01
Sponsor: Livzon Pharmaceutical Group Inc.
Active, not recruiting
SARS-CoV-2 Vaccination in Kidney Transplant Recipients-Stratified Analysis of the Humoral Immune Response - CONCLUSIONS: Apart from immunosuppressive therapy, the humoral vaccination response is largely affected by nonmodifiable factors in kidney transplant recipients. With the currently leading and clinically easier Omicron variant, this puts into perspective the strategy to significantly enhance the protective efficacy of the available vaccines by reducing or temporarily stopping proliferation inhibitors, not least considering the inherent rejection risk with a possible deterioration of graft…
Microbiome analysis revealing microbial interactions and secondary bacterial infections in COVID-19 patients co-morbidly affected by type 2 diabetes - CONCLUSIONS: The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19 infected diabetic patients, although few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal-flora and probiotics through dietary supplementation and excessive inflammation reduction by preventing secondary infections might lead to a better outcome for those co-morbid patients. This article is protected by…
DNA damage contributes to age-associated differences in SARS-CoV-2 infection - Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to disproportionately affect older individuals. How aging processes affect SARS-CoV-2 infection and disease progression remains largely unknown. Here, we found that DNA damage, one of the hallmarks of aging, promoted SARS-CoV-2 infection in vitro and in vivo. SARS-CoV-2 entry was facilitated by DNA damage caused by extrinsic genotoxic stress or telomere dysfunction and…
Effects of natural polymorphisms in SARS-CoV-2 RNA-dependent RNA polymerase on its activity and sensitivity to inhibitors in vitro - SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is the key enzyme required for viral replication and mRNA synthesis. RdRp is one of the most conserved viral proteins and a promising target for antiviral drugs and inhibitors. At the same time, analysis of public databases reveals multiple variants of SARS-CoV-2 genomes with substitutions in the catalytic RdRp subunit nsp12. Structural mapping of these mutations suggests that some of them may affect the interactions of nsp12 with its cofactors…
Xuanfei Baidu Formula attenuates LPS-induced acute lung injury by inhibiting the NF-κB signaling pathway - CONCLUSION: This study identified the potential practical components of XFBD, combined with network pharmacology and experimental validation to demonstrate that XFBD can alleviate lung injury caused by ALI by inhibiting the NF-κB signaling pathway.
Does income inequality reshape the environmental Kuznets curve (EKC) hypothesis? A nonlinear panel data analysis - The COVID-19 pandemic has further increased income inequality. This work is aimed to explore the impact of income inequality on the environmental Kuznets curve (EKC) hypothesis. To this end, income inequality is set as the threshold variable, economic growth is set as the explanatory variable, while carbon emission is set as the explained variable, and the threshold panel model is developed using the data of 56 countries. The empirical results show that income inequality has changed the…
Astersaponin I from Aster koraiensis is a natural viral fusion blocker that inhibit the infection of SARS-CoV-2 variants and syncytium formation - The continuous emergence of SARS-CoV-2 variants prolongs COVID-19 pandemic. Although SARS-CoV-2 vaccines and therapeutics are currently available, there is still a need for development of safe and effective drugs against SARS-CoV-2 and also for preparedness for the next pandemic. Here, we discover that astersaponin I (AI), a triterpenoid saponin in Aster koraiensis inhibits SARS-CoV-2 entry pathways at the plasma membrane and within the endosomal compartments mainly by increasing cholesterol…
Role of CCL2/CCR2 axis in the pathogenesis of COVID-19 and possible Treatments: All options on the Table - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is cause of the novel coronavirus disease (COVID-19). In the last two years, SARS-CoV-2 has infected millions of people worldwide with different waves, resulting in the death of many individuals. The evidence disclosed that the host immune responses to SARS-CoV-2 play a pivotal role in COVID-19 pathogenesis and clinical manifestations. In addition to inducing antiviral immune responses, SARS-CoV-2 can also cause dysregulated…
Trim69 is a microtubule regulator that acts as a pantropic viral inhibitor - Through a screen that combines functional and evolutionary analyses, we identified tripartite motif protein (Trim69), a poorly studied member of the Trim family, as a negative regulator of HIV-1 infection in interferon (IFN)-stimulated myeloid cells. Trim69 inhibits the early phases of infection of HIV-1, but also of HIV-2 and SIV(MAC) in addition to the negative and positive-strand RNA viruses vesicular stomatitis virus and severe acute respiratory syndrome coronavirus 2, with magnitudes that…
Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS - CONCLUSIONS: Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.
In-silico structural inhibition of ACE-2 binding site of SARS-CoV-2 and SARS-CoV-2 Omicron spike protein by lectin antiviral dyad system to treat COVID-19 - Spike glycoprotein of SARS-CoV-2 binds ACE-2 receptors via its receptor-binding-domain (RBD) and mediates virus-to-host cell fusion. Recently emerged omicron variant of SARS-CoV-2 possess around 30 mutations in spike protein where N501Y tremendously increases viral infectivity and transmission. Lectins interact with glycoproteins and mediate innate immunity displaying antiviral, antibacterial and anticarcinogenic properties. In this study, we analysed the potential of lectin, and lectin-antibody…
Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2 - New pathogens responsible for novel human disease outbreaks in the last two decades are mainly the respiratory system viruses. Not different was the last pandemic episode, caused by infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One of the extensively explored targets, in the recent scientific literature, as a possible way for rapid development of COVID-19 specific drug(s) is the interaction between the receptor-binding domain of the virus’ spike (S) glycoprotein…
Atovaquone for treatment of COVID-19: A prospective randomized, double-blind, placebo-controlled clinical trial - Background: An in silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (M^(pro)), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to…
Achieving sustainability: Determinants of conscious green purchasing behavior during the COVID-19 pandemic - The COVID-19 pandemic has spread worldwide, resulting in crises in public health and sustainable development. Aimed at understanding the determinants of conscious green purchasing behavior (GPB), this paper developed a comprehensive framework linking the moderating effect of negative environmental affective reactions (NEAR) to COVID-19 based on the S-O-R paradigm. Using randomly selected urban residents from China’s Yangtze River Delta and Bohai Rim regions, the empirical study was conducted…
Antiviral Effects of Heparan Sulfate Analogue-Modified Two-Dimensional MXene Nanocomposites on PRRSV and SARS-CoV-2 - Due to the worldwide impact of viruses such as SARS-CoV-2, researchers have paid extensive attention to antiviral reagents against viruses. Despite extensive research on two-dimensional (2D) transition metal carbides (MXenes) in the field of biomaterials, their antiviral effects have received little attention. In this work, heparan sulfate analogue (sodium 3-mercapto-1-propanesulfonate, MPS) modified 2D MXene nanocomposites (Ti(3)C(2)-Au-MPS) for prevention of viral infection are prepared and…