Wastewater surveillance is anticipated to be a representative and timely method to assess infectious disease status; however, its influence on public perception and behavior remains unclear. Therefore, in this study, we used a randomized controlled trial to analyze the influence of wastewater surveillance-based information on understanding of, interest in, relief regarding, preventive behavioral intention against, and subsequent online search behavior related to coronavirus disease 2019 (COVID-19). Valid responses were obtained from 1,000 individuals in both control and intervention groups from Yahoo crowdsourcing users aged ≥18 years in Japan. This survey was conducted from August 4 to August 7, 2023, just before the common Japanese tradition of returning to hometowns. The questionnaire not only collected personal attributes but also gauged responses to COVID-19 information. This information highlighted the early detection capabilities and representativeness of wastewater surveillance compared with sentinel surveillance at medical institutions. At one-week post-survey, we obtained the survey participants9 online search history for key words such as “bullet train,” “highway,” “airplane,” and “wastewater.” The findings showed no significant differences between the two groups in terms of COVID-19 interest or preventive behavior before information provision, verifying the effectiveness of participant randomization. Wastewater surveillance-based information did not notably elevate understanding or specific intentions regarding COVID-19, such as wearing masks and receiving vaccination. However, it significantly increased interest in, relief concerning the infection status, and general preventive behavioral intentions. Heightened interest and general preventive intentions did not depend on prior interest or behavior. However, those who previously engaged in preventive behavior or who were less interested in COVID-19 exhibited more relief after exposure to wastewater surveillance-based information. Furthermore, this information could slightly influence online searches related to return travel modes, such as highways. In conclusion, information from wastewater surveillance effectively shapes individual perceptions of and responses to infections.
Background COVID-19 vaccines reduce the risk of severe disease, but it is less clear what effect vaccines have on reducing the risk of infection in high contact settings like households, alone or in combination with prior infection. Methods Households with an individual who tested positive for SARS-CoV-2 during Sep 2021-May 2023 were screened nationwide and at 7 sentinel sites and enrolled if the index cases illness onset was ≤6 days prior. Household members had daily self-collected nasal swabs tested by RT-PCR for SARS-CoV-2. COVID-19 vaccination status was assessed by plausible self-report (with date) or vaccination records. Prior infection was assessed by self-reported prior testing and by anti-nucleocapsid antibodies presence at enrollment. The effects of prior immunity, including vaccination, prior infection, or hybrid immunity (both vaccination and prior infection) on SARS-CoV-2 infection risk among household contacts were assessed by robust, clustered multivariable Poisson regression. Findings There were 1,532 contacts from 905 households included in this analysis. Of these, 67% were enrolled May-November 2022, when Omicron BA.4/5 predominated. Most contacts (89%) had some immunity to SARS-CoV-2 at the time of household exposure: 8% had immunity from prior infection alone, 51% from vaccination alone, and 29% had hybrid immunity. Sixty percent of contacts tested SARS-CoV-2-positive during follow-up. The risk of SARS-CoV-2 infection was not significantly reduced by vaccination but was reduced among those with prior infection considering such immunity separately (adjusted relative risk 0.83; 95% confidence interval: 0.77, 0.90); however, when accounting for both sources of immunity, only contacts with vaccination and prior infection had significantly reduced risk of infection (aRR: 0.81, 95% CI: 0.70, 0.93). The risk of infection was lower when the last immunizing event (vaccination or infection) occurred ≤6 months before COVID-19 affected the household (aRR: 0.69, 95% CI: 0.57, 0.83). Interpretation Immunity from COVID-19 vaccination and prior infection was synergistic in protecting household contacts from SARS-CoV-2 infection. These data support COVID-19 vaccination, even for those who have been previously infected.
Symptoms post- SARS-CoV-2 infection may persist for months and cause significant impairment and impact to quality of life. Acute symptoms of SARS-CoV-2 infection are well studied, yet data on clusters of symptoms over time, or postacute sequelae of SARS-CoV-2 infection (PASC), are limited. We aim to characterize PASC phenotypes by identifying symptom clusters over a six-month period following infection in individuals vaccinated (boosted and not) and those unvaccinated. Subjects with ≥1 self-reported symptom and positive RT-PCR for SARS-CoV-2 at CVS Health US test sites were recruited between January and April 2022. Patient-reported outcomes symptoms, heath-related quality of life (QoL), work productivity and activity impairment (WPAI) were captured at 1 month, 3 months, and 6 months post-acute infection. Logistic regression and latent class analysis (LCA) were performed on 20 symptoms using baseline socio-demographic, clinical characteristics, and vaccination status as well as EQ-5and WPAI results as covariables. Subjects with more symptoms were associated with lower health-related quality of life, and worse WPAI scores. LCA identified three phenotypes that are primarily differentiated by number of symptoms. These three phenotypes remained consistent across time periods. Vaccinated individuals were more likely to be in the low symptom burden latent classes at all time points compared to unvaccinated individuals.
Many individuals experience persistent symptoms such as deteriorated physical and mental health, increased fatigue, and reduced cognitive performance months after recovering from COVID-19. Current data are limited on the long-term trajectory of these symptoms and their prevalence in milder cases. Our study aimed to assess the persistent effects of COVID-19 on physical and mental health, fatigue, and cognitive performance in a cohort of 214 students, averaging 21.8 years of age. Of these, 148 had contracted COVID-19 but were not hospitalized, with the time since infection ranging from 1 to 39 months. We utilized a comprehensive panel of cognitive tests to measure intelligence, memory, and psychomotor skills, and a detailed anamnestic questionnaire to evaluate physical and mental health. While contracting COVID-19 did not significantly impact overall health and performance, it was associated with increased reports of fatigue. However, the reported severity of the disease had a pronounced negative influence on physical health, mental well-being, fatigue, and reaction time. Trends of improvement in physical and mental health, as well as error rate, were observed within the first two years post-infection. However, fatigue and reaction time showed a trend of deterioration. Beyond the two-year mark, physical health and error rate continued to improve, while mental health began to deteriorate. Fatigue and reaction time continued to decline. Overall, our findings suggest that some effects of contracting COVID-19 can persist or even deteriorate over time, even in younger individuals who had mild cases that did not require hospitalization.
Summary Background The effectiveness of different strategies in addressing the COVID-19 pandemic has been assessed, but there is still not enough evidence in Asian countries. This study aims to examine the factors influencing the trajectory of COVID-19 evolution in Asia, to provide insights for optimizing public health policies. Methods In this longitudinal analysis, we combined COVID-19 cases and vaccination percentages from Our Word in Data with the policy stringency index from the Oxford COVID-19 Government Response Tracker for 12 Asian countries between January 1, 2021, and September 30, 2022. An agglomerative hierarchical cluster analysis (HCA) was conducted to identify countries with similar COVID-19 evolution trajectories. We also investigated the potential impact of seasonal variations on the virus9 trajectory. The relationship between the level of policy response, vaccination coverage, and COVID-19 cases was explored using Generalized Additive Models (GAMs). Findings There were noticeable differences in the evolution trajectory of COVID-19 among the countries. The 12 Asian countries were grouped into two clusters based on evolutionary similarities. Cluster 1 consisted of West Asian countries (Azerbaijan, Turkey, Bahrain, Israel and Lebanon); while Cluster 2 included Japan, South Korea, Singapore, Malaysia, Thailand, Cambodia and Indonesia. The analysis revealed that the stringency index and vaccination coverage were associated with a statistically significant impact (both P values < 0.0001) on the evolution trajectory of COVID-19 (adjR2=0.54). The dose-response relationships demonstrated that the continuous high levels of stringency index (≥87.6) or vaccination coverage (≥ 42.0%) have led to a decrease in COVID-19 infection rates. In early 2021, the adjR2 increased to 0.93 for all countries. Furthermore, the adjR2 for Cluster 1 and Cluster 2 were 0.86 and 0.90 respectively. All GAMs models have significantly improved compared to null model (P values <0.0001). Interpretation By strengthening vaccination ahead of susceptible seasons and enhancing personal self-protection measures, the transmission of COVID-19 among the population can be reduced even during the highly infectious Omicron era.
Due to a combination of asymptomatic or undiagnosed infections, the proportion of the United States population infected with SARS-CoV-2 was unclear from the beginning of the pandemic. We previously established a platform to screen for SARS-CoV-2 positivity across a representative proportion of the US population, from which we reported that almost 17 million Americans were estimated to have had undocumented infections in the Spring of 2020. Since then, vaccine rollout and prevalence of different SARS-CoV-2 variants have further altered seropositivity trends within the United States population. To explore the longitudinal impacts of the pandemic and vaccine responses on seropositivity, we re-enrolled participants from our baseline study in a 6- and 12- month follow-up study to develop a longitudinal antibody profile capable of representing seropositivity within the United States during a critical period just prior to and during the initiation of vaccine rollout. Initial measurements showed that, since July 2020, seropositivity elevated within this population from 4.8% at baseline to 36.2% and 89.3% at 6 and 12 months, respectively. We also evaluated nucleocapsid seropositivity and compared to spike seropositivity to identify trends in infection versus vaccination relative to baseline. These data serve as a window into a critical timeframe within the COVID-19 pandemic response and serve as a resource that could be used in subsequent respiratory illness outbreaks.
Background The COVID-19 pandemic has affected millions of people globally with major health, social and economic consequences, prompting development of vaccines for use in the general population. However, vaccination uptake is lower in some groups, including in pregnant women, because of concerns regarding vaccine safety. There is evidence of increased risk of adverse pregnancy and neonatal outcomes associated with SARS-CoV-2 infection, but fear of vaccine-associated adverse events on the baby both in short and longer term is one of the main drivers of low uptake for this group. Other vaccines commonly used in pregnancy include influenza and pertussis. These both have reportedly higher uptake compared with COVID-19 vaccination, which may be because they are perceived to be safer. In this study, we will undertake an independent evaluation of the uptake, effectiveness and safety of COVID-19 vaccinations in pregnant women using the QResearch primary care database in England. Objectives A. To determine COVID-19 vaccine uptake in pregnant women compared to uptake of influenza and pertussis vaccinations. B. To estimate COVID-19 vaccine effectiveness in pregnant women by evaluating the risk of severe COVID-19 outcomes following vaccination. C. To assess the safety of COVID-19 vaccination in pregnancy by evaluating the risks of adverse pregnancy and perinatal outcomes and adverse events of special interest for vaccine safety after COVID-19 vaccination compared with influenza and pertussis vaccinations. Methods This population-based study uses the QResearch database of primary health care records, linked to individual-level data on hospital admissions, mortality, COVID-19 vaccination, SARS-CoV-2 testing data and congenital anomalies. We will include women aged 16 to 49 years with at least one pregnancy during the study period of 30th December 2020 to the latest date available. Babies born during the study period will be identified and linked to the mothers record, where possible. We will describe vaccine uptake in pregnant women by trimester and population subgroups defined by demographics and other characteristics. Cox proportional hazards multivariable regression will be used to identify factors associated with vaccine uptake. The effectiveness of COVID-19 vaccines in pregnant women will be assessed using time varying Royston-Palmar regression analyses to determine unadjusted and adjusted hazard ratios for the occurrence of severe COVID-19 outcomes after each vaccine dose compared with unvaccinated individuals. For the safety analysis, we will we use logistic regression analyses to determine unadjusted and adjusted odds ratios for the occurrence of maternal (e.g. miscarriage, ectopic pregnancy and gestational diabetes) and perinatal outcomes (e.g. stillbirth, small for gestational age and congenital anomalies) by vaccination status compared to unvaccinated individuals. For the adverse events of special interest for vaccine safety (e.g. venous thromboembolism, myocarditis and Guillain Barre syndrome), we will use time varying Royston-Palmar regression analyses to determine unadjusted and adjusted hazard ratios for the occurrence of each outcome by vaccination status to unvaccinated individuals. Ethics and dissemination QResearch is a Research Ethics Approved Research Database with ongoing approval from the East Midlands Multi-Centre Research Ethics Committee (Ref: 18/EM/0400). This study was approved by the QResearch Scientific Committee on 9th June 2022. This research protocol has been developed with support from a patient and public involvement panel, who will continue to provide input throughout the duration of the study. Research findings will be submitted to pre-print servers such as MedRxIv, academic publication and disseminated more broadly through media releases and community groups and conference presentations.
Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+ T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+ CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI associate with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.
Wastewater surveillance is a powerful tool for monitoring the prevalence of infectious disease. Systems for wastewater monitoring were put in place throughout the world during the COVID-19 pandemic. These systems use viral RNA copies as the basis of estimates of COVID-19 cases in the sewershed area, thereby providing data critical for public health responses. However, the potential to measure other biomarkers in wastewater during outbreaks has not been fully explored. Here we report a novel approach for detecting specific human antibodies from wastewater. We measured the abundance of anti-SARS-CoV-2 spike IgG and IgA from fresh samples of community wastewater and from archived frozen samples dating from 2020-22. The assay described can be performed with readily available reagents, at a moderate per-sample cost. Our findings demonstrate the feasibility of noninvasive serological surveillance via wastewater, enabling a new approach to immunity-based monitoring of populations.
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
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- A Pilot Investigation. - Conditions: Long COVID
Interventions: Device: PrO2
Sponsors: University of Bath; Swansea University
Not yet 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
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
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
Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants - Conditions: COVID-19 Respiratory Infection
Interventions: Drug: GST-HG171/ritonavir; Drug: ritonavir
Sponsors: Fujian Akeylink Biotechnology Co., Ltd.
Active, not recruiting
Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments - Conditions: Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome; COVID-19; Fatigue; Fatigue Syndrome, Chronic
Interventions: Device: Monoplace Hyperbaric Chamber (Class III medical device).
Sponsors: Sunnybrook Health Sciences Centre
Not yet recruiting
Education of Medical Staff to Post Acute Covid susTained sYmptoms - Conditions: Post-acute COVID-19 Syndrome
Interventions: Other: Training in the management of functional disorders; Other: Reimbursement of 3 long consultations
Sponsors: Assistance Publique - Hôpitaux de Paris; ANRS, Emerging Infectious Diseases
Not yet recruiting
Pharmacist Management of Paxlovid eVisits - Conditions: COVID-19; Quality of Care
Interventions: Other: Pharmacist Care; Other: AFM Pool Care
Sponsors: Kaiser Permanente
Not yet recruiting
tDCS in the Management of Post-COVID Disorders - Conditions: Long COVID
Interventions: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training
Sponsors: Universidade Federal de Pernambuco; São Paulo State University
Recruiting
Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol - Conditions: COVID-19; Influenza
Interventions: Other: Fact box
Sponsors: Harding Center for Risk Literacy
Not yet recruiting
Humoral immune response to SARS-CoV-2 and endemic coronaviruses in urban and indigenous children in Colombia - CONCLUSIONS: Overall, antibody titers, but in particular ACE2 binding inhibition are low within Colombian samples, requiring further investigation to determine any potential clinical significance.
ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2 - Apoptosis signal-regulating kinase 1 (ASK1)/MAP3K5 is a stress response kinase that is activated by various stimuli. It is known as an upstream activator of p38- Mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) that are reactive oxygen species (ROS)-induced kinases. Accumulating evidence show that ROS accumulate in virus-infected cells. Here, we investigated the relationship between viruses and ASK1/p38MAPK or ASK1/JNK pathways. Our findings suggest that virus…
Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract - CONCLUSIONS: Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production, and administration of interferon alpha-14 may be attractive transmission-blocking interventions.
Assembly of SARS-CoV-2 ribonucleosomes by truncated N* variant of the nucleocapsid protein - The Nucleocapsid (N) protein of SARS-CoV-2 compacts the RNA genome into viral ribonucleoprotein (vRNP) complexes within virions. Assembly of vRNPs is inhibited by phosphorylation of the N protein SR region. Several SARS-CoV-2 variants of concern carry N protein mutations that reduce phosphorylation and enhance the efficiency of viral packaging. Variants of the dominant B.1.1 viral lineage also encode a truncated N protein, termed N* or Δ(1-209), that mediates genome packaging despite lacking the…
Update on fungal lipid biosynthesis inhibitors as antifungal agents - Fungal diseases today represent a world-wide problem. Poor hygiene and decreased immunity are the main reasons behind the manifestation of this disease. After COVID-19, an increase in the rate of fungal infection has been observed in different countries. Different classes of antifungal agents, such as polyenes, azoles, echinocandins, and anti-metabolites, as well as their combinations, are currently employed to treat fungal diseases; these drugs are effective but can cause some side effects and…
Assessment of virus and Leptospira carriage in bats in France - With over 1,400 species worldwide, bats represent the second largest order of mammals after rodents, and are known to host major zoonotic pathogens. Here, we estimate the presence of pathogens in autochthonous bat populations. First, we set out to check our samples for PCR amplification efficiency by assessing the occurrence of inhibited PCR reactions from different types of bat samples with amplifying the housekeeping gene β-actin. Second, we investigated the presence of five targeted pathogens…
Blocking of doublecortin-like kinase 1-regulated SARS-CoV-2 replication cycle restores cell signaling network - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to fatal outcomes for subgroups of patients with pre-existing co-morbidities. We previously reported a significant association between high expression levels of a cancer stem cell protein, doublecortin-like kinase 1 (DCLK1), in the lungs and macrophages of SARS-CoV-2-infected patients and the severity of coronavirus disease 2019 (COVID-19). Herein, we demonstrate a pivotal role of DCLK1 in the viral replication cycle…
In Silico Screening of Some Active Phytochemicals to Identify Promising Inhibitors Against SARS-CoV-2 Targets - CONCLUSION: The present in silico screening study suggested that active phytomolecules from medicinal plants could inhibit SARS-CoV-2 targets. The elite docked compounds with drug-like properties have a harmless ADMET profile, which may help to develop promising COVID-19 inhibitors.
The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity - The SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localizes to mitochondria, where it inhibits innate immunity by restricting IFN-β…
Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors - A class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC(50) range of…
Antiviral Effects of Micafungin against Pteropine Orthoreovirus, an Emerging Zoonotic Virus Carried by Bats - Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, and/or beta coronavirus. Pteropine orthoreovirus (PRV), whose spillover event occurred from fruits bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is an effective tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic…
Cellular assays for dynamic quantification of deubiquitinase activity and inhibition - Deubiquitinases (DUBs) are proteolytic enzymes that catalyze the removal of ubiquitin from protein substrates. The critical role of DUBs in regulating protein ubiquitination makes them attractive drug targets in oncology, neurodegenerative disease, and antiviral development. Biochemical assays for quantifying DUB activity have enabled characterization of substrate preferences and discovery of small molecule inhibitors. However, assessing the efficacy of these inhibitors in cellular contexts to…
Transporter modulation of molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-brain barrier in a rat - CONCLUSIONS: In summary, molnupiravir rapidly transforms into NHC and crosses the BBB and reaches the brain at approximately 0.3-0.8% of the blood‒brain ratio. The maximum concentration of NHC in the blood and brain is above the average half maximal inhibitory concentration (IC50) of the drug required to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, suggesting a therapeutic effect. The penetration of NHC is modulated by NBMPR. These findings provide constructive…
Evaluation and Mechanistic Investigation of Human Milk Oligosaccharide against SARS-CoV-2 - Four human milk oligosaccharides (HMOs), 3’-sialyllactose (3’-SL), 6’-sialyllactose (6’-SL), 2’-fucosyllactose (2’-FL), and 3-fucosyllactose (3-FL), were assessed for their possible antiviral activity against the SARS-CoV-2 spike receptor binding domain (RBD) in vitro. Among them, only 2’-FL/3-FL exhibited obvious antibinding activity against direct binding and trans-binding in competitive immunocytochemistry and enzyme-linked immunosorbent assays. The antiviral effects of 2’-FL/3-FL were…
Explore intersection genes of oxymatrine and COVID-19 with lung cancer as potential therapeutic targets based on network pharmacology - Introduction. Oxymatrine is a natural quinazine alkaloid extracted from Sophora flavescens and has many medicinal values. Oxymatrine showed protective effects, viral inhibition and effects against lung cancer.Hypothesis/Gap Statement. Individuals with lung cancer exhibit heightened vulnerability to COVID-19 infection due to compromised immune function. In conjunction with COVID-19, it is hypothesized that oxymatrine may exert potent pharmacological effects on lung cancer patients.Aim. The…