- Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing -
X-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. In this work, we present a workflow implemented at a laboratory CT setup, using semi-automated data acquisition, reconstruction and statistical quantification of lung tissue in an early screen of Covid-19 drug candidates. Different drugs were tested in a hamster model after SARS-CoV-2 infection. To make full use of the recorded high-throughput XPCT data, we then used morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing invaluable insights into the pathological progression and partial recovery due to drug treatment.
- Gaining Biological Insights through Supervised Data Visualization -
Dimensionality reduction-based data visualization is pivotal in comprehending complex biological data. The most common methods, such as PHATE, t-SNE, and UMAP, are unsupervised and therefore reflect the dominant structure in the data, which may be independent of expert-provided labels. Here we introduce a supervised data visualization method called RF-PHATE, which integrates expert knowledge for further exploration of the data. RF-PHATE leverages random forests to capture intricate feature-label relationships. Extracting information from the forest, RF-PHATE generates low-dimensional visualizations that highlight relevant data relationships while disregarding extraneous features. This approach scales to large datasets and applies to classification and regression. We illustrate RF-PHATE’s prowess through three case studies. In a multiple sclerosis study using longitudinal clinical and imaging data, RF-PHATE unveils a sub-group of patients with non-benign relapsing-remitting Multiple Sclerosis, demonstrating its aptitude for time-series data. In the context of Raman spectral data, RF-PHATE effectively showcases the impact of antioxidants on diesel exhaust-exposed lung cells, highlighting its proficiency in noisy environments. Furthermore, RF-PHATE aligns established geometric structures with COVID-19 patient outcomes, enriching interpretability in a hierarchical manner.
- Mis- and Disinformation during the 2021 Canadian Federal Election -
The Canadian Election Misinformation Project was a civil society and academic partnership that aimed to rapidly identify and respond to mis- and disinformation incidents during the 44th Canadian Federal Election while evaluating the extent to which these incidents impact the attitudes and behaviours of Canadians. It also sought to develop understanding of the types and consequences of misleading and false information circulating in the public sphere in addition to supporting world-class research into the dynamics of the information ecosystem and the broad impacts of misinformation on Canadian democracy. The data shows that: 1) Although there was widespread misinformation during the 2021 Canadian federal election, the overall election was minimally impacted by mis- and disinformation; 2) Most Canadians believe the election was safe from foreign interference and that misinformation played a minimal role in the election; 3) Communities that previously focused on sharing COVID-19 misinformation adopted conspiracy theories about a broader set of topics during the election, including vaccines, climate change, and the integrity of the election; and 4) Nevertheless, a strong majority of Canadians believe that misinformation is a threat to Canadian democracy, polarizes Canadians, and threatens social cohesion.
- Public Health Communication and Engagement on Social Media during the COVID-19 Pandemic -
Social media provides governments the opportunity to directly communicate with their constituents. During a pandemic, reaching as many citizens as possible with health messaging is critical to reducing the spread of the disease. This study evaluates efforts to spread healthcare information by Canadian local, provincial, and federal governments during the first five months of the COVID-19 pandemic. We collect all health-related communications coming from government accounts on Facebook and Twitter and analyze the data using a nested mixed method approach. We first identify quantifiable features linked with citizen engagement, before subsequently performing content analysis on outlier posts. We make two critical contributions to existing knowledge about government communication, particularly during public health crises. We identify cross-platform variations in strategy effectiveness and draw attention to specific, evidence-based practices that can increase engagement with government health information.
- All in this together: deservingness of government aid during the COVID-19 pandemic -
The COVID-19 pandemic has placed unprecedented pressure on governments to engage in widespread cash transfers directly to citizens to help mitigate economic losses. These programs are major redistribution efforts aimed at a variety of sub-groups within society (the unemployed, those with children, those with pre-existing health conditions, etc.) and there has been remarkably little resistance to these government outlays. We employ a novel and pre-registered paired vignette experiment to assess support for government aid during the pandemic in a large, nationally representative sample. We evaluate whether the “normal” deservingness hierarchy and considerations of social affinity or material self-interest continue to drive preferences of Canadians regarding redistribution. We find only small deservingness considerations and little evidence that redistribution preferences are informed by similarity considerations. Instead, we find broad, generous, and non-discriminatory support for direct cash transfers during this period of crisis.
- The Causes and Consequences of COVID-19 Misperceptions: Understanding the Role of News and Social Media -
We investigate the relationship between media consumption, misinformation, and important attitudes and behaviours during the COVID-19 pandemic in Canada. We find that comparatively more misinformation circulates on social media platforms, while traditional news media tend to reinforce public health recommendations like social distancing. We find that exposure to social media is associated with misperceptions about COVID-19 while the inverse is true for news media. These misperceptions are in turn associated with lower compliance with social distancing measures. We thus draw a link from misinformation on social media to behaviours and attitudes that potentially magnify the scale and lethality of COVID-19.
- The lasting earnings losses of COVID-19 short-time work -
This study is the first to investigate the impact of short-time work (STW) schemes during the COVID-19 pandemic on earnings after STW. STW schemes were implemented to preserve employee–employer matches, support workers’ incomes, and uphold consumption. Although workers faced temporary earnings losses under STW, it is unclear if the negative earnings effects of STW persisted or were limited to the STW spell. Therefore, this study uses a dynamic difference-in-difference (DiD) identification strategy with administrative data to identify any lasting STW effects on earnings. This approach accounts for factors that influenced worker selection into STW and tests for heterogeneous effects across subgroups of workers. We find lasting earnings losses that persisted beyond the STW participation itself. Most importantly, these earnings losses depended on the duration of STW exposure, with greater negative effects being more prominent in cases of long-term or recurring STW spells. Lasting, post-STW earnings losses tended to be more pronounced for white-collar jobs, while the largest losses were observed among men with blue-collar jobs whose STW spells exceeded one year.
- Revealing the drivers of antibiotic resistance trends in Streptococcus pneumoniae amidst the 2020 COVID-19 pandemic: Insights from mathematical modeling -
Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built in into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
- Persistence and Free Chlorine Disinfection of Human Coronaviruses and Their Surrogates in Water -
The COVID-19 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses to humans, but the literature is relatively void of studies on the persistence of many viruses, especially coronaviruses, in water and their susceptibility to chlorine disinfection. To fill that knowledge gap, we evaluated the persistence and free chlorine disinfection of human coronavirus OC43 (HCoV-OC43) and its surrogates, murine hepatitis virus (MHV) and porcine transmissible gastroenteritis virus (TGEV), in drinking water and laboratory buffer using cell culture methods. The decay rate constants of human coronavirus and its surrogates in water varied depending on virus and water matrix. In drinking water prior to disinfectant addition, MHV showed the largest decay rate constant (2.25 day-1) followed by HCoV-OC43 (0.99 day-1) and TGEV (0.65 day-1); while in phosphate buffer, HCoV-OC43 (0.51 day-1) had a larger decay rate constant than MHV (0.28 day-1) and TGEV (0.24 day-1). Upon free chlorine disinfection, the inactivation rates of coronaviruses were independent of free chlorine concentration and not affected by water matrix, though they still varied between viruses. TGEV showed the highest susceptibility to free chlorine disinfection with the inactivation rate constant of 113.50 mg-1 min-1 L, followed by MHV (81.33 mg-1 min-1 L) and HCoV-OC43 (59.42 mg-1 min-1 L).
- A Bacteriophage Cocktail Targeting Yersinia pestis Provides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model -
Yersinia pestis, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity, Y. pestis is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug resistant strains. The dissemination of such Y. pestis strains could be catastrophic, with public health consequences far more daunting than those caused by the recent COVID-19 pandemic. Thus, there is an urgent need to develop novel, safe, and effective treatment approaches for managing Y. pestis infections. This includes infections by antigenically distinct strains for which vaccines, none FDA approved yet, may not be effective, and those that cannot be controlled by approved antibiotics. Lytic bacteriophages provide one such alternative approach. In this study, we examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by Y. pestis CO92. YPP-401 is a four-phage preparation with a 100% lytic activity against a panel of 68 genetically diverse Y. pestis strains. Using a pneumonic plague aerosol challenge model in gender-balanced Brown Norway rats, YPP-401 demonstrated ~88% protection when delivered 18 hours post-exposure for each of two administration routes (i.e., intraperitoneal and intranasal) in a dose-dependent manner. Our studies suggest that YPP-401 could provide an innovative, safe, and effective approach for managing Y. pestis infections, including those caused by naturally occurring or intentionally developed strains that cannot be managed by vaccines in development and antibiotics.
- GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern -
Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 s of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how the structural role of this glycan changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
- Phase 1 of the NIH Preprint Pilot: Testing the viability of making preprints discoverable in PubMed Central and PubMed -
Introduction: The National Library of Medicine (NLM) launched a pilot in June 2020 to 1) explore the feasibility and utility of adding preprints to PubMed Central (PMC) and making them discoverable in PubMed and 2) to support accelerated discoverability of NIH-supported research without compromising user trust in NLM’s widely used literature services. Methods: The first phase of the Pilot focused on archiving preprints reporting NIH-supported SARS-CoV-2 virus and COVID-19 research. To launch Phase 1, NLM identified eligible preprint servers and developed processes for identifying NIH-supported preprints within scope in these servers. Processes were also developed for the ingest and conversion of preprints in PMC and to send corresponding records to PubMed. User interfaces were modified for display of preprint records. NLM collected data on the preprints ingested and discovery of preprint records in PMC and PubMed and engaged users through focus groups and a survey to obtain direct feedback on the Pilot and perceptions of preprints. Results: Between June 2020 and June 2022, NLM added more than 3,300 preprint records to PMC and PubMed, which were viewed 4 million times and 3 million times, respectively. Nearly a quarter of preprints in the Pilot were not associated with a peer-reviewed published journal article. User feedback revealed that the inclusion of preprints did not have a notable impact on trust in PMC or PubMed. Discussion: NIH-supported preprints can be identified and added to PMC and PubMed without disrupting existing operations processes. Additionally, inclusion of preprints in PMC and PubMed accelerates discovery of NIH research without reducing trust in NLM literature services. Phase 1 of the Pilot provided a useful testbed for studying NIH investigator preprint posting practices, as well as knowledge gaps among user groups, during the COVID-19 public health emergency, an unusual time with heightened interest in immediate access to research results.
- Deciphering the Molecular Mechanism of Post-Acute Sequelae of COVID-19 through Comorbidity Network Analysis -
Introduction: The post-acute sequelae of COVID-19 presents a significant health challenge in the post-pandemic world. Our study aims to analyze longitudinal electronic health records to determine the impact of COVID-19 on disease progression, provide molecular insights into these mechanisms, and identify associated biomarkers. Method: We included 58,710 patients with COVID-19 records from 01/01/2020 to 31/08/2022 and at least one hospital admission before and after the acute phase of COVID-19 (28 days) as the treatment group. A healthy control group of 174,071 individuals was established for comparison using propensity score matching based on pre-existing diseases (before COVID-19). We built a comorbidity network using Pearson correlation coefficient differences between pairs of pre-existing disease and post-infection disease in both groups. Disease-protein mapping and protein-protein interaction network analysis revealed the impact of COVID-19 on disease trajectories through protein interactions in the human body. Results: The disparity in the weight of prevalent disease comorbidity patterns between the treatment and control groups highlights the impact of COVID-19. Certain specific comorbidity patterns show a more pronounced influence by COVID-19. For each comorbidity pattern, overlapping proteins directly associated with pre-existing diseases, post-infection diseases, and COVID-19 help to elucidate the biological mechanism of COVID-19's impact on each comorbidity pattern. Proteins essential for explaining the biological mechanism can be identified based on their weights. Conclusion: Disease comorbidity associations influenced by COVID-19, as identified through longitudinal electronic health records and disease-protein mapping, can help elucidate the biological mechanisms of COVID-19, discover intervention methods, and decode the molecular basis of comorbidity associations. This analysis can also yield potential biomarkers and corresponding treatments for specific disease patterns.
- Changes in wild meat hunting and use by rural communities during the COVID-19 socio-economic shock -
There has been limited quantitative research into the effects of socio-economic shocks on biological resource use. Focusing on wild meat hunting, a substantial livelihood and food source in tropical regions, we evaluated the impacts of the shock from Nigeria’s COVID-19 lockdown on species exploitation around a global biodiversity hotspot. Using a three-year quantitative dataset collected during and after the lockdown (covering 1,008 hunter-months) and matching by time of year, we found that successful hunting trip rates were more frequent during lockdown, with a corresponding increase in the monthly number, mass, and value of animals caught. Moreover, hunters consumed a larger proportion of wild meat and sold less during lockdown compared to non-lockdown periods. These results suggest that local communities relied on wild meat to supplement reduced food and income during lockdown, buffering COVID-19’s socio-economic shock. Our findings also indicate that wild species may be especially vulnerable to increased hunting pressure during such shocks.
- Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection -
Inflammation-induced thrombosis is a common consequence of bacterial and viral infections, such as those caused by Salmonella Typhimurium (STm) and SARS-CoV-2. The identification of multi-organ thrombosis and the chronological differences in its induction and resolution raise significant challenges for successfully targeting multi-organ infection-associated thrombosis. Here, we identified specific pathways and effector cells driving thrombosis in the spleen and liver following STm infection. Thrombosis in the spleen is independent of IFN-{gamma} or the platelet C-type lectin-like receptor CLEC-2, while both molecules were previously identified as key drivers of thrombosis in the liver. Furthermore, we identified platelets, monocytes, and neutrophils as core constituents of thrombi in both organs. Depleting neutrophils or monocytic cells independently abrogated thrombus formation. Nevertheless, blocking TNF, which is expressed by both myeloid cell types, diminished both thrombosis and inflammation which correlates with reduced endothelial expression of E-selectin and leukocyte infiltration. Moreover, tissue factor and P-selectin glycoprotein ligand 1 inhibition impairs thrombosis in both spleen and liver, identifying multiple common checkpoints to target multi-organ thrombosis. Therefore, organ-specific, and broad mechanisms driving thrombosis potentially allow tailored treatments based on the clinical need and to define the most adequate strategy to target both thrombosis and inflammation associated with systemic infections.
Diet and Fasting for Long COVID - Conditions: Long Covid19; Long COVID
Interventions: Other: Low sugar diet and 10-12 hour eating window; Other: Low sugar diet, 8 hour eating window and fasting
Sponsors: Pacific Northwest University of Health Sciences
Recruiting
The Effectiveness of a Health Promotion Program for Older People With Post-Covid-19 Sarcopenia - Conditions: Post COVID-19 Condition
Interventions: Other: Protein powder and Resistance exercise
Sponsors: Mahidol University; National Health Security Office, Thailand
Not yet recruiting
Chronic-disease Self-management Program in Patients Living With Long-COVID in Puerto Rico - Conditions: Long Covid19
Interventions: Other: “Tomando control de su salud” (Spanish Chronic Disease Self-Management)
Sponsors: University of Puerto Rico; National Institutes of Health (NIH)
Recruiting
Treatment of Persistent Post-Covid-19 Smell and Taste Disorders - Conditions: Post-covid-19 Persistent Smell and Taste Disorders
Interventions: Drug: Cerebrolysin; Other: olfactory and gustatory trainings
Sponsors: Sherifa Ahmed Hamed
Completed
A Study to Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults - Conditions: COVID-19; COVID-19 Immunisation
Interventions: Biological: TI-0010; Biological: Placebo
Sponsors: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna
Recruiting
Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction - Conditions: Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders
Interventions: Drug: Sodium Citrate; Drug: Normal Saline; Other: Olfactory Training Kit - “The Olfactory Kit, by AdvancedRx”
Sponsors: University of North Carolina, Chapel Hill
Recruiting
Phase II, Double Blind, Randomized Trial of CX-4945 in Viral Community Acquired Pneumonia - Conditions: Community-acquired Pneumonia; SARS-CoV-2 -Associated Pneumonia; Influenza With Pneumonia
Interventions: Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: CX-4945 (Influenza virus domain); Drug: Placebo (Influenza virus domain)
Sponsors: Senhwa Biosciences, Inc.
Not yet recruiting
Edge AI-deployed DIGItal Twins for PREDICTing Disease Progression and Need for Early Intervention in Infectious and Cardiovascular Diseases Beyond COVID-19 - Investigation of Biomarkers in Dermal Interstitial Fluid - Conditions: Heart Failure
Interventions: Device: Use of the PELSA System for dISF extraction
Sponsors: Charite University, Berlin, Germany
Not yet recruiting
Phase III Clinical Study Evaluating the Efficacy and Safety of WPV01 in Patients With Mild/Moderate COVID-19 - Conditions: Mild to Moderate COVID-19
Interventions: Drug: WPV01; Drug: Placebo
Sponsors: Westlake Pharmaceuticals (Hangzhou) Co., Ltd.
Recruiting
Integrated Mindfulness-based Health Qigong Intervention for COVID-19 Survivors and Caregivers - Conditions: COVID-19 Infection
Interventions: Other: Mindfulness-based Health Qigong Intervention
Sponsors: The Hong Kong Polytechnic University
Recruiting
Measuring Variant-Specific Neutralizing Antibody Profiles after Bivalent SARS-CoV-2 Vaccinations Using a Multivariant Surrogate Virus Neutralization Microarray - The capability of antibodies to neutralize different SARS-CoV-2 variants varies among individuals depending on the previous exposure to wild-type or Omicron-specific immunogens by mono- or bivalent vaccinations or infections. Such profiles of neutralizing antibodies (nAbs) usually have to be assessed via laborious live-virus neutralization tests (NTs). We therefore analyzed whether a novel multivariant surrogate-virus neutralization test (sVNT) (adapted from a commercial microarray) that…
RBD-Protein/Peptide Vaccine UB-612 Elicits Mucosal and Fc-Mediated Antibody Responses against SARS-CoV-2 in Cynomolgus Macaques - Antibodies provide critical protective immunity against COVID-19, and the Fc-mediated effector functions and mucosal antibodies also contribute to the protection. To expand the characterization of humoral immunity stimulated by subunit protein-peptide COVID-19 vaccine UB-612, preclinical studies in non-human primates were undertaken to investigate mucosal secretion and the effector functionality of vaccine-induced antibodies in antibody-dependent monocyte phagocytosis (ADMP) and…
RNF5: inhibiting antiviral immunity and shaping virus life cycle - RNF5 is an E3 ubiquitin ligase involved in various physiological processes such as protein localization and cancer progression. Recent studies have shown that RNF5 significantly inhibits antiviral innate immunity by promoting the ubiquitination and degradation of STING and MAVS, which are essential adaptor proteins, as well as their downstream signal IRF3. The abundance of RNF5 is delicately regulated by both host factors and viruses. Host factors have been found to restrict RNF5-mediated…
Role of probiotics in managing various human diseases, from oral pathology to cancer and gastrointestinal diseases - The imbalance of microbial composition and diversity in favor of pathogenic microorganisms combined with a loss of beneficial gut microbiota taxa results from factors such as age, diet, antimicrobial administration for different infections, other underlying medical conditions, etc. Probiotics are known for their capacity to improve health by stimulating the indigenous gut microbiota, enhancing host immunity resistance to infection, helping digestion, and carrying out various other functions….
Prospective Antiviral Effect of Ulva lactuca Aqueous Extract against COVID-19 Infection - Marine algal extracts exhibit a potent inhibitory effect against several enveloped and non-enveloped viruses. The infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has several adverse effects, including an increased mortality rate. The anti-COVID-19 agents are still limited; this issue requires exploring novel, effective anti-SARS-CoV-2 therapeutic approaches. This study investigated the antiviral activity of an aqueous extract of Ulva lactuca, which was collected from…
Anastrozole Protects against Human Coronavirus Infection by Ameliorating the Reactive Oxygen Species-Mediated Inflammatory Response - The common human coronavirus (HCoV) exhibits mild disease with upper respiratory infection and common cold symptoms. HCoV-OC43, one of the HCoVs, can be used to screen drug candidates against SARS-CoV-2. We determined the antiviral effects of FDA/EMA-approved drug anastrozole (AZ) on two human coronaviruses, HCoV-OC43 and HCoV-229E, using MRC-5 cells in vitro. The AZ exhibited antiviral effects against HCoV-OC43 and HCoV-229E infection. Subsequent studies focused on HCoV-OC43, which is related…
ACE2 improves endothelial cell function and reduces acute lung injury by downregulating FAK expression - Endothelial cell (EC) barrier dysfunction and increased adhesion of immune inflammatory cells to ECs crucially contribute to acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2) is an essential regulator of the renin-angiotensin system (RAS) and exerts characteristic vasodilatory and anti-inflammatory effects. SARS-COV-2 infects the lungs by binding to ACE2, which can lead to dysregulation of ACE2 expression, further leading to ALI with predominantly vascular inflammation and…
Analyzing the impact of COVID-19 on consumption behaviors through recession and recovery patterns - The COVID-19 outbreak has dramatically impacted the economy, particularly consumption behaviors. Studies on how consumption responses to COVID-19 can be a powerful aid for urban consumption recovery. In this paper, based on a high-frequency consumption dataset from January 6, 2020, to April 28, 2020 covering 18 sectors and dataset from the corresponding lunar period in 2021, we look at how COVID-19 changed how people spent their money by looking at patterns of recession and recovery during the…
Informatics and Computational Approaches for the Discovery and Optimization of Natural Product-Inspired Inhibitors of the SARS-CoV-2 2’-O-Methyltransferase - The urgent need for new classes of orally available, safe, and effective antivirals─covering a breadth of emerging viruses─is evidenced by the loss of life and economic challenges created by the HIV-1 and SARS-CoV-2 pandemics. As frontline interventions, small-molecule antivirals can be deployed prophylactically or postinfection to control the initial spread of outbreaks by reducing transmissibility and symptom severity. Natural products have an impressive track record of success as prototypic…
Identifying novel inhibitors targeting Exportin-1 for the potential treatment of COVID-19 - The nuclear export protein 1 (XPO1) mediates the nucleocytoplasmic transport of proteins and ribonucleic acids (RNAs) and plays a prominent role in maintaining cellular homeostasis. XPO1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses. In our earlier study, we proved the inhibition of XPO1 as a therapeutic strategy for managing SARS-COV-2 and its variants. In this study, we have utilized pharmacophore-assisted computational methods to identify…
Klotho-derived peptide KP1 ameliorates SARS-CoV-2-associated acute kidney injury - Introduction: The severe cases of COVID-19, a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), often present with acute kidney injury (AKI). Although old age and preexisting medical conditions have been identified as principal risk factors for COVID-19-associated AKI, the molecular basis behind such a connection remains unknown. In this study, we investigated the pathogenic role of Klotho deficiency in COVID-19-associated AKI and explored the therapeutic potential…
Peptidyl nitroalkene inhibitors of main protease rationalized by computational and crystallographic investigations as antivirals against SARS-CoV-2 - The coronavirus disease 2019 (COVID-19) pandemic continues to represent a global public health issue. The viral main protease (M^(pro)) represents one of the most attractive targets for the development of antiviral drugs. Herein we report peptidyl nitroalkenes exhibiting enzyme inhibitory activity against M^(pro) (K(i): 1-10 μM) good anti-SARS-CoV-2 infection activity in the low micromolar range (EC(50): 1-12 μM) without significant toxicity. Additional kinetic studies of compounds FGA145,…
Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity - Due to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated…
Quantitative comparison of nuclear transport inhibition by SARS coronavirus ORF6 reveals the importance of oligomerization - Open Reading Frame 6 (ORF6) proteins, which are unique to severe acute respiratory syndrome-related (SARS) coronavirus, inhibit the classical nuclear import pathway to antagonize host antiviral responses. Several alternative models were proposed to explain the inhibitory function of ORF6 [H. Xia et al., Cell Rep. 33, 108234 (2020); L. Miorin et al., Proc. Natl. Acad. Sci. U.S.A. 117, 28344-28354 (2020); and M. Frieman et al., J. Virol. 81, 9812-9824 (2007)]. To distinguish these models and build…
NF9 peptide specific cytotoxic T lymphocyte clone cross react to Y453F mutation of SARS-CoV-2 virus spike protein - The recognition by cytotoxic T cells (CTLs) is essential for the clearance of SARS-CoV-2 virus-infected cells. Several viral proteins have been described to be recognized by CTLs. Among them, the spike (S) protein is one of the immunogenic proteins. The S protein acts as a ligand for its receptors, and several mutants with different affinities for its cognate receptors have been reported, and certain mutations in the S protein, such as L452R and Y453F, have been found to inhibit the…