Individual and societal reactions to an ongoing pandemic can lead to social dilemmas: In some cases, each individual is tempted to not follow an intervention, but for the whole society it would be best if they did. Now that in most countries the extent of regulations to reduce SARS-CoV-2 transmission is very small, interventions are driven by individual decision-making. Assuming that individuals act in their best own interest, we propose a framework in which this situation can be quantified, depending on the protection the intervention provides to a user and to others, the risk of getting infected, and the costs of the intervention. We discuss when a tension between individual and societal benefits arises and which parameter comparisons are important to distinguish between different regimes of intervention use.
Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as Long COVID. The underlying pathophysiology of Long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of COVID infection and certain other post-COVID sequelae, their potential role in Long COVID is important to investigate. Here we apply a well-established, unbiased, proteome-wide autoantibody detection technology (PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with Long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected which separates individuals with prior COVID infection from those never exposed to COVID, we did not detect patterns of autoreactivity that separate individuals with Long COVID relative to individuals fully recovered from SARS-CoV-2 infection. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and Long COVID was apparent by this assay.
Background: Widespread use of at-home COVID-19 tests hampers determination of community COVID-19 incidence. Using nationwide data available through the US National Wastewater Surveillance System, we examined the performance of two wastewater metrics in predicting high case and hospitalizations rates both before and after widespread use of at-home tests. Methods: We performed area under the receiver operating characteristic (ROC) curve analysis (AUC) for two wastewater metrics- viral concentration relative to the peak of January 2022 (9wastewater percentile9) and 15-day percent change in SARS-CoV-2 (9percent change9). Dichotomized reported cases (equal to or greater than 200 or <200 cases per 100,000) and new hospitalizations (equal to or greater than 10 or <10 per 100,000) were our dependent variables, stratified by calendar quarter. Using logistic regression, we assessed the performance of combining wastewater metrics. Results: Among 268 counties across 22 states, wastewater percentile detected high reported case and hospitalizations rates in the first quarter of 2022 (AUC 0.95 and 0.86 respectively) whereas the percent change did not (AUC 0.54 and 0.49 respectively). A wastewater percentile of 51% maximized sensitivity (0.93) and specificity (0.82) for detecting high case rates. A model inclusive of both metrics performed no better than using wastewater percentile alone. The predictive capability of wastewater percentile declined over time (AUC 0.84 and 0.72 for cases for second and third quarters of 2022). Conclusion: Nationwide, county wastewater levels above 51% relative to the historic peak predicted high COVID rates and hospitalization in the first quarter of 2022, but performed less well in subsequent quarters. Decline over time in predictive performance of this metric likely reflects underreporting of cases, reduced testing, and possibly lower virulence of infection due to vaccines and treatments.
Introduction: COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of immense global public health concern. RP7214, a novel, potent, oral, inhibitor of DHODH, has shown preclinical evidence in inhibiting viral replication and lung inflammation. Methods: This was a randomized, double-blind, placebo-controlled phase 2 study in patients with symptomatic mild SARS-CoV-2 infection, having at least one high-risk feature (e.g., hypertension, diabetes mellitus) for developing severe Covid-19 infection. The patients received RP7214 (400 mg BID) or a placebo for 14 days in a blinded fashion and were followed up to 30 days. Patients also received supportive therapy (e.g., antipyretics and antitussives for symptomatic relief) at the discretion of the investigator. The endpoints were Covid 19 related hospitalization rate by Day 15, SARS-CoV-2 viral load and clearance on Days 3,7 and 15, clinical symptoms improvement by Day 15, safety, and the immuno-modulatory effect of RP7214. Results: A total of 163 patients were treated in the study; 82 received RP7214 and 81 received placebo. Of the total patients, 44.2% had received Covid-19 vaccine prior to the study. The symptom onset was ≤ 3 days in 22.1%. None of the patients in the study required hospitalization. There was no difference in the mean change of viral load between RP7214 and placebo. In the subgroup analysis, in patients having symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Days 3 and 7, respectively. Similarly, in non-vaccinated patients with symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Day 3. Overall, there was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. For all other endpoints, there was no difference between RP7214 and placebo. Majority of the reported AEs were mild and not related either to study treatment. Conclusions: RP7214 at 400 mg BID dose level showed a statistically significant reduction in viral load at an early stage of the disease and in non-vaccinated patients. There was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. RP7214 showed a favorable safety profile. Further development of RP7214 in Covid 19 in a mild symptomatic population with co-morbidities and treated at an early stage of disease may show benefit. Keywords: RP7214; DHODH inhibitor; COVID-19; SARS-CoV-2.
It is quite well-documented that the COVID-19 pandemic disrupted cancer screening services in all countries, irrespective of their resources and healthcare settings. While quantitative estimates on reduction in volume of screening tests or diagnostic evaluation are readily available from the high-income countries, very little data is available from the low- and middle-income countries (LMICs). From the CanScreen5 global cancer screening data repository we identified six LMICs through purposive sampling based on the availability of cancer screening data at least for the years 2019 and 2020. These countries represented different human development index (HDI) categories and were from Asia (Bangladesh and Thailand), Africa (Morocco) and Latin America (Argentina and Colombia). The reduction in the volume of tests in 2020 compared to the previous years ranged from 14.1% in Bangladesh to 72.9% in Argentina (regional programme) for cervical screening, from 14.1% in Bangladesh to 52.2% in Morocco for breast cancer screening and 30.7% in Thailand for colorectal cancer screening. Number of colposcopies was reduced in 2020 compared to previous year by 88.9% in Argentina, 38.2% in Colombia, 27.4% in Bangladesh and 52.3% in Morocco. The reduction in detection rates of CIN 2 or worse lesions ranged from 20.7% in Morocco to 45.4% in Argentina. Reduction of breast cancer detection by 19.2% was reported from Morocco. No association of the impact of pandemic could be seen with HDI categories. Quantifying the impact of service disruptions in screening and diagnostic tests will allow the programmes to strategize how to ramp up services to clear the backlogs in screening and more crucially in further evaluation of screen-positives. The data can be used to estimate the impact on stage distribution and avoidable mortality from these common cancers.
Background: The Danish national SARS-CoV-2 mass test system was among the most ambitious worldwide. We describe its set-up and analyse differences in patterns of testing per demography and time period in relation to the three waves of SARS-CoV-2 transmission in Denmark. Methods: We included all reported PCR- and rapid antigen-tests performed between 27 February 2020 and 10 March 2022 among all residents aged 2 years or above. Descriptive statistics and Poisson regression models were used to analyse characteristics of individuals tested for SARS-CoV-2 using a national cohort study design. Results: A total of 63.7 million PCR-tests and 60.0 million antigen-tests were performed in the study period, testing 91.1% and 79.2% of the Danish population at least once by PCR or antigen, respectively. Female sex, younger age, Danish heritage and living in the capital area were all factors positively associated with the frequency of PCR-testing. The association between COVID-19 vaccination and PCR-testing changed from negative to positive over time. Conclusion: We provide details of the widely available, free-of-charge, national SARS-CoV-2 test system, which served to identify infected individuals, assist isolation of infectious individuals and contact tracing, and thereby mitigating the spread of SARS-CoV-2 in the Danish population. The test system was utilized by nearly the entire population at least once, and widely accepted across different demographic groups. However, demographic differences in the test uptake did exist and should be considered in order not to cause biases in studies related to SARS-CoV-2, e.g., studies of transmission and vaccine effectiveness.
As demonstrated during the SARS-CoV-2 pandemic, detecting and tracking the emergence and spread of pathogen variants is an important component of monitoring infectious disease outbreaks. Pathogen genome sequencing has emerged as the primary tool for variant characterization, so it is important to consider the number of sequences needed when designing surveillance programs or studies, both to ensure accurate conclusions and to optimize use of limited resources. However, current approaches to calculating sample size for variant monitoring often do not account for the biological and logistical processes that can bias which infections are detected and which samples are ultimately selected for sequencing. In this manuscript, we introduce a framework that models the full process from infection detection to variant characterization and demonstrate how to use this framework to calculate appropriate sample sizes for sequencing-based surveillance studies. We consider both cross-sectional and continuous sampling, and we have implemented our method in a publicly available tool that allows users to estimate necessary sample sizes given a specific aim (e.g., variant detection or measuring variant prevalence) and sampling method. Our framework is designed to be easy to use, while also flexible enough to be adapted to other pathogens and surveillance scenarios.
The pandemic of Coronavirus disease 2019 (COVID-19) has lasted more than two years and caused millions of deaths. While the characteristics and outcomes have been more widely studied in the adult population, we conducted an in-depth analysis via the 2020 National Inpatient Sample to understand the characteristics and predictors for the use of mechanical ventilation in patients of ages 18 and less in the United States. Twenty-two thousand four hundred ninety hospitalizations involving COVID-19-positive children were found. 52.7% (11850 cases) were females, 37.0% were Hispanics, 38.0% (8555 cases) were in the first percentile 0-25th of Median household income, and 66.9% used Medicaid. In total, 1140 cases (5.1%) needed mechanical ventilation. Among factors such as obesity (aOR 1.662, 95%CI 1.368-2.019, p<0.001), Blacks (vs. White) (aOR 1.472, 95%CI 1.23-1.761, p<0.001), private insurances (aOR 1.241, 95%CI 1.06-1.453, p=0.007) or remaining forms of payment other than Medicaid or private insurances (aOR 1.763, 95%CI 1.428-2.177, p<0.001, vs. Medicaid), ages 6 to 10 years (aOR 1.531, 95%CI 1.259-1.862, p<0.001, vs. ages 0-5) showed higher odds of needing mechanical ventilation. On the contrary, Females (aOR 0.54, 95%CI 0.472-0.617, p<0.001, vs. Males), hospitalized patients in November (aOR 0.542, 95%CI 0.399-0.736, p<0.001) and December (aOR 0.446, 95%CI 0.329-0.606, p<0.001) (vs. April), Hispanics (aOR 0.832, 95%CI 0.699-0.99, p=0.038, vs. White), ages 16-18 years (aOR 0.804, 95%CI 0.673-0.96, p=0.016, vs. 0-5years), and in the 76th-100th median household income percentile (aOR 0.783, 95%CI 0.628-0.976, p=0.03, vs. 0-25th percentile) showed reduced odds. 9.6% of patients on mechanical ventilation died.
Serological population surveillance can elucidate immunity landscapes against SARS-CoV-2 variants and are critical in monitoring infectious disease spread, evolution, and outbreak risks. However, current serological tests fall short of capturing complex humoral immune responses from different communities. Here, we report a machine-learning (ML)-aided nanobiosensor that can simultaneously quantify antibodies against the ancestral strain and Omicron variants of SARS-CoV-2 with epitope resolution. Our approach is based on a multiplexed, rapid, and label-free nanoplasmonic biosensor, which can detect past infection and vaccination status and is sensitive to SARS-CoV-2 variants. After training an ML model with antigen-specific antibody datasets from four COVID-19 immunity groups (naive, convalescent, vaccinated, and convalescent-vaccinated), we tested our approach on 100 blind blood samples collected in Dane County, WI. Our results are consistent with public epidemiological data, demonstrating that our user-friendly and field-deployable nanobiosensor can capture community-representative public health trends and help manage COVID-19 and future outbreaks.
Background: Short-term forecasts of all-cause mortality are used retrospectively to estimate the baseline mortality and to obtain excess death after mortality shocks, such as heatwaves and pandemics, have occurred. In this study we propose a flexible method to forecast all-cause mortality in real-time and to rapidly identify short-term changes in all-cause mortality seasonal patterns within an epidemiological year. Methods: We use all-cause monthly death counts and ratios of death counts between adjacent months as inputs. The ratio between one month (earlier month) and the consecutive month (later month) is called later/earlier ratio. We forecast the deaths one-month-ahead based on their proportion to the previous month, defined by the average later/earlier ratio over the preceding years. We provide forecasting intervals by way of a bootstrapping procedure. Results: The method is applied to monthly mortality data for Denmark, France, Spain, and Sweden from 2012 through 2022. Over the epidemiological years before COVID-19, the method captures the variations in winter and summer mortality peaks. The results reflect the synchrony of COVID-19 waves and the corresponding mortality burdens in the four analyzed countries. The forecasts show a higher level of accuracy compared to traditional models for short-term forecasting, i.e., 5-year-average method and Serfling model. Conclusion: The method proposed is attractive for health researchers and governmental offices to aid public health responses, because it uses minimal input data, i.e., monthly all-cause mortality data, which are timely available and comparable across countries.
Whilst it is now widely recognised that routine immunisation (RI) was disrupted by the COVID-19 pandemic in 2020 compared to previous immunisation performance, the extent of continued interruptions in 2021 and/or rebounds to previous trends remains unclear, with sporadic surveys reporting signs of immunisation system recovery at the end of 2020. We modelled country-specific RI trends using validated estimates of national coverage from the World Health Organisation and United Nation Children9s Fund for over 160 countries, to project expected diphtheria, tetanus, and pertussis-containing vaccine first-dose (DTP1), third-dose (DTP3) and measles-containing vaccine first-dose (MCV1) coverage for 2021 based on pre-pandemic trends (from 2000-2019). We estimated a 3.6% (95%CI: [2.6%; 4.6%]) decline in global DTP3 coverage in 2021 compared to 2000-2019 trends, from an expected 90.1% to a reported 86.5% across 164 reporting countries, and similar results for DTP1 (2.8% decline; 95%CI: [2.0%; 3.6%]), and for MCV1 (3.8% decline; 95%CI: [4.8%; 2.7%]). 86.5% global coverage in 2021 represents a further decrease from that reported in 2020 and 2019, and translates to a 16-year setback in RI coverage, i.e., 2005 levels. Hypothesised and early signals of rebounds to pre-pandemic coverage were not seen in most countries. The Americas, Africa, and Asia were the most impacted regions, with low- and middle-income countries the most affected income groups. The number of Zero Dose children also continued to increase in 2021. DTP1 coverage declined worldwide from an expected 93.7% to a reported 90.9% (2.8% decline; 95%CI: [2.0%; 3.6%]) which translates into an additional 3.4 million Zero Dose children on top of an expected 11.0 million (30.9% increase) at the global level. We hope this work will provide an objective baseline to inform future interventions and prioritisation aiming to facilitate rebounds in coverage to previous levels and catch-up of growing populations of under- and un-immunised children.
Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine - Condition: COVID-19
Intervention: Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation
Sponsors: Wuhan BravoVax Co., Ltd.; National University Hospital, Singapore; Shanghai BravoBio Co., Ltd.
Not yet recruiting
Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care - Condition: COVID-19
Intervention: Drug: Plitidepsin
Sponsor: PharmaMar
Not yet recruiting
COVID-19 Self-testing Study - Condition: COVID-19
Intervention: Behavioral: SMARTest mobile app for COVID-19 self-testing
Sponsor: Columbia University
Recruiting
Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2 - Condition: COVID-19
Intervention: Drug: AZD 1222
Sponsors: Botswana Harvard AIDS Institute Partnership; AstraZeneca; Botswana Ministry of Health
Completed
Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19 - Condition: COVID-19
Interventions: Drug: GS-5245; Drug: GS-5245 Placebo
Sponsor: Gilead Sciences
Not yet recruiting
INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19 - Condition: COVID-19
Intervention: Device: HIGH FREQUENCY CHEST WALL OSCILLATION
Sponsor: Cairo University
Not yet recruiting
A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19 - Condition: COVID-19
Interventions: Drug: HH-120 nasal spray; Drug: Placebo Comparator
Sponsor: Huahui Health
Recruiting
Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection - Condition: COVID-19
Interventions: Drug: VV116+SOC; Drug: SOC
Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd
Recruiting
Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19) - Condition: COVID-19
Interventions: Drug: STI-1558; Drug: STI-1558 placebo
Sponsor: Zhejiang ACEA Pharmaceutical Co. Ltd.
Not yet recruiting
Pirfenidone in Adult Hospitalized Patients With COVID-19 - Condition: COVID-19 Pneumonia
Interventions: Drug: Pirfenidone Oral Product; Drug: Pirfenidone placebo
Sponsor: Capital Medical University
Active, not recruiting
Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19 - Condition: Long COVID-19
Intervention: Biological: UC-MSCs
Sponsor: Shanghai East Hospital
Not yet recruiting
The Effectiveness of a Health Education Intervention to Reduce Anxiety in Quarantined COVID-19 Patients - Condition: Health Education, COVID-19, Quarantine, Anxiety, Pandemic
Intervention: Other: health education intervention
Sponsor: University of Monastir
Completed
The Difference Between Non-invasive High-frequency Oscillatory Ventilation and Non-invasive Continuous Airway Pressure Ventilation in COVID-19 With Acute Hypoxemia - Conditions: COVID-19 Pneumonia; Non-invasive Ventilation
Interventions: Device: Non-invasive high-frequency oscillatory ventilation; Device: Non-invasive continuous positive airway pressure ventilation
Sponsor: Guangzhou Institute of Respiratory Disease
Not yet recruiting
COVID-19 Molecular OTC At Home Test - Condition: COVID-19 Pandemic
Intervention: Diagnostic Test: Diagnostic Test: IN Vitro
Sponsor: 3EO Health
Not yet recruiting
Randomized-controlled Trial of Immunoadsorption (IA) in Patients With Chronic Fatigue Syndrome (CFS) Including Patients With Post-COVID-19 CFS (PACS-CFS) - Condition: ME/CSF Including CFS Related to Post-acute COVID-19 Syndrome (PACS)
Intervention: Device: Immunoadsorption
Sponsor: Charite University, Berlin, Germany
Not yet recruiting
Mini-review: Angiotensin- converting enzyme 1 (ACE1) and the impact for diseases such as Alzheimer’s disease, sarcopenia, cancer, and COVID-19 - Ageing has been associated with comorbidities, systemic low-grade of inflammation, and immunosenescence. Hypertension is the most common morbidity and anti-hypertensives are used for more than 50%. Angiotensin-converting enzyme 1 inhibitors (ACEi) and angiotensin II receptor blockers (ARB) control blood pressure but also seem to play a role in comorbidities such as Alzheimer’s disease, sarcopenia and cancer. The impact of anti-hypertensives in comorbidities is due to the expression of…
Role of innate and acquired resilience in behavioral system, mental health, and internet addiction among Japanese adolescents in the COVID-19 pandemic - BACKGROUND: This study examines mediation models in which behavioral inhibition and activation systems (BIS/BAS) impact internet addiction through mental health and the moderating roles of innate and acquired resilience in the models.
Aloin A inhibits SARS CoV-2 replication by targeting its binding with ACE2 - Evidence from modeling-supported molecular dynamics simulation - The current study aimed to expand on the recently published results and assess the inhibitory efficacy of aloin A against SARS CoV-2. In vitro testing of aloin A against SARS CoV-2 proteases (i.e., M^(Pro) and PL^(Pro)) showed weak to moderate activity (IC(50) = 68.56 ± 1.13 µM and 24.77 ± 1.57 µM, respectively). However, aloin A was able to inhibit the replication of SARS CoV-2 in Vero E6 cells efficiently with an IC(50) of 0.095 ± 0.022 µM. Depending on the reported poor permeability of aloin…
SARS-CoV-2 NSP7 inhibits type I and III IFN production by targeting the RIG-I/MDA5, TRIF, and STING signaling pathways - SARS-CoV-2 is a poor inducer of innate antiviral immunity, and the underlying mechanism still needs further investigation. Here, we reported that SARS-CoV-2 NSP7 inhibited the production of type I and III IFNs by targeting the RIG-I/MDA5, TLR3-TRIF, and cGAS-STING signaling pathways. SARS-CoV-2 NSP7 suppressed the expression of IFNs and IFN-stimulated genes induced by poly (I:C) transfection and infection with Sendai virus or SARS-CoV-2 virus-like particles. NSP7 impaired type I and III IFN…
Modulation of transient receptor potential (TRP) channels by plant derived substances used in over-the-counter cough and cold remedies - CONCLUSIONS: The literature suggests that these plant derived substances have multifaceted actions and can interact with the TRP ‘cough’ receptors. The plant derived substances used in cough and cold medicines have the potential to target multiple symptoms experienced during a cold.
Potential antiviral effects of pantethine against SARS-CoV-2 - SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection, in Vero E6 cells and in Calu-3a cells. Pantethine reduced the infection of cells by SARS-CoV-2 in…
Liposome-based high-throughput and point-of-care assays toward the quick, simple, and sensitive detection of neutralizing antibodies against SARS-CoV-2 in patient sera - The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in 2019 caused an increased interest in neutralizing antibody tests to determine the immune status of the population. Standard live-virus-based neutralization assays such as plaque-reduction assays or pseudovirus neutralization tests cannot be adapted to the point-of-care (POC). Accordingly, tests quantifying competitive binding inhibition of the angiotensin-converting enzyme 2 (ACE2) receptor to the…
Effect of acetic acid inactivation of SARS-CoV-2 - Effective measures are needed to prevent the spread and infectivity of SARS-CoV-2 that causes COVID-19. Chemical inactivation may help to prevent the spread and transmission of this and other viruses. Hence, we tested the SARS-CoV-2 antiviral activity of acetic acid, the main component of vinegar, in vitro. Inactivation and binding assays suggest that acetic acid is virucidal. We found that 6% acetic acid, a concentration typically found in white distilled vinegar, effectively inactivated…
Protease-Responsive Potential-Tunable AIEgens for Cell Selective Imaging of TMPRSS2 and Accurate Inhibitor Screening - Transmembrane protease serine 2 (TMPRSS2) is a plasma membrane protease that activates both spike protein of coronaviruses for cell entry and oncogenic signaling pathways for tumor progression. TMPRSS2 inhibition can reduce cancer invasion and metastasis and partially prevent the entry of SARS-CoV-2 into host cells. Thus, there is an urgent need for both TMPRSS2-selective imaging and precise screening of TMPRSS2 inhibitors. Here, we report a TMPRSS2-responsive surface-potential-tunable…
Effects of Epitranscriptomic RNA Modifications on the Catalytic Activity of SARS-CoV-2 Replication Complex - SARS-CoV-2 causes individualized symptoms. Many reasons have been given. We propose that an individual’s epitranscriptomic system could be responsible as well. The viral RNA genome can be subject to epitranscriptomic modifications, the modifications can be different for different individuals, and thus epitranscriptomics can affect many events including RNA replication differently. In this context, we studied the effects of modifications including pseudouridine (Ψ), 5methylcytosine (m5C),…
How much (evil) intelligence can be encoded by 30 kb? - Genomes of most RNA viruses are rarely larger than the size of an average human gene (10-15 kb) and still code for a number of biologically active polypeptides that modify the immune system and metabolism of the host organism in an amazingly complex way. Prolonged coevolution developed tricks by which viruses can dodge many protective mechanisms of the host and lead to the formation of molecular mimicry patterns. Some viruses inhibit the interferon response, interfere with the membrane…
Rhenium(V) Complexes as Cysteine-Targeting Coordinate Covalent Warheads - Interest in covalent enzyme inhibitors as therapeutic agents has seen a recent resurgence. Covalent enzyme inhibitors typically possess an organic functional group that reacts with a key feature of the target enzyme, often a nucleophilic cysteine residue. Herein, the application of small, modular Re^(V) complexes as inorganic cysteine-targeting warheads is described. These metal complexes were found to react with cysteine residues rapidly and selectively. To demonstrate the utility of these…
Heterogeneous Nuclear Protein U Degraded the m6A Methylated TRAF3 Transcript by YTHDF2 To Promote Porcine Epidemic Diarrhea Virus Replication - Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the Coronaviridae family and can cause fatal watery diarrhea in piglets, causing significant economic losses. Heterogeneous nuclear protein U (HNRNPU) is a novel RNA sensor involved in sensing viral RNA in the nucleus and mediating antiviral immunity. However, it remains elusive whether and how cytoplasmic PEDV can be sensed by the RNA sensor HNRNPU. In this study we determined that HNRNPU was the binding partner of…
DFT calculations, molecular docking, in vitro antimicrobial and antidiabetic studies of green synthesized Schiff bases: as Covid-19 inhibitor - In this investigation, we synthesized Schiff bases 2-(2-methoxyphenoxy)-N-(4-methylbenzylidene)ethanamine, N-(4-methoxybenzylidene)-2-(2-methoxyphenoxy)ethanamine and 2-(2-methoxyphenoxy)-N-(4-nitrobenzylidene)ethanamine from 2-(2-methoxyphenoxy)ethanamine and various aromatic aldehydes by the environmentally friendly sonication method. The B3LYP method with a 6-311++G (d, p) basis set was used in the DFT calculation to obtain the optimized structure of the Schiff base MPEA-NIT. The compounds…
COVID-19: Understanding the impact of anti-hypertensive drugs and hydroxychloroquine on the ACE1 and ACE2 in lung and adipose tissue in SHR and WKY rats - Hypertensive individuals taking anti-hypertensive drugs from renin-angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS-CoV-2 virus (COVID-19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10 mg/kg/day) or…