Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Factors associated with severe acute respiratory syndrome-related coronavirus 2 infection in unvaccinated children and young adults -

  BACKGROUND: Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC). METHODS: We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults <25 years between November 2020-May 2021 and phase 2 enrolled children <10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity. RESULTS: A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups). CONCLUSION: SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms.

  🖺 Full Text HTML: Factors associated with severe acute respiratory syndrome-related coronavirus 2 infection in unvaccinated children and young adults
• A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes -

  Molnupiravir, an antiviral medication that has been widely used against SARS-CoV-2, acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus, and many will be lethal, and so molnupiravir-induced elevated mutation rates reduce viral load. However, if some patients treated with molnupiravir do not fully clear SARS-CoV-2 infections, there could be the potential for onward transmission of molnupiravir-mutated viruses. Here we show that SARS-CoV-2 sequencing databases contain extensive evidence of molnupiravir mutagenesis. Using a systematic approach, we find that a specific class of long phylogenetic branches, distinguished by a high proportion of G-to-A and C-to-T mutations, appear almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age-groups with widespread usage of the drug. We identify a mutational spectrum, with preferred nucleotide contexts, from viruses in patients known to have been treated with molnupiravir and show that its signature matches that seen in these long branches, in some cases with onwards transmission of molnupiravir-derived lineages. Finally, we analyse treatment records to confirm a direct association between these high G-to-A branches and the use of molnupiravir.

  🖺 Full Text HTML: A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes
• How reliable are estimates of key parameters in viral dynamic models? -
  Mathematical models of viral infection have been developed and fit to data to gain insight into disease pathogenesis for a number of agents including HIV, hepatitis C and B virus. However, for acute infections such as influenza and SARS-CoV-2, as well as for infections such as hepatitis C and B that can be acute or progress to being chronic, viral load data are often collected after symptoms develop, usually around or after the peak viral load. Consequently, we frequently lack data in the exponential phase of viral growth, i.e., when most transmission events occur. Missing data may make estimation of the time of infection, the infectious period, and parameters in viral dynamic models, such as the cell infection rate, difficult. Here, we evaluated the reliability of estimates of key model parameters when viral load data prior to the viral load peak is missing. We estimated the time from infection to peak viral load by fitting non-linear mixed models to a dataset with frequent viral RNA measurements, including pre-peak. We quantified the reliability of estimated infection times, key model parameters, and the time to peak viral load. Although estimates of the time of infection are sensitive to the quality and amount of available data, other parameters important in understanding disease pathogenesis, such as the loss rate of infected cells, are less sensitive. We find a lack of data in the exponential growth phase underestimates the time to peak viral load by several days leading to a shorter predicted exponential growth phase. On the other hand, having an idea of the time of infection and fixing it, results in relatively good estimates of dynamical parameters even in the absence of early data.
  🖺 Full Text HTML: How reliable are estimates of key parameters in viral dynamic models?
• Purification, crystallization, and preliminary structural analysis of multivalent immunogenic effector protein-anchored SARS-CoV-2 RBD -
  The continuous spread of highly transmissible variants of concern and the potential diminished effectiveness of existing vaccines necessitate ongoing research and development of new vaccines. Immunogenic molecule-anchored antigen has demonstrated superior efficacy in subunit vaccination, primarily due to enhanced cellular uptake facilitated by the affinity between the surface of Immunogenic molecule and the cell membrane. Based on the Immunogenic recombinase B. malayi RecA (BmRecA), we have overexpressed the construct of BmRecA with SARS-CoV-2 RBD (BmRecA-RBD) that exists as a stable helical filament formation; it was purified and crystallized to obtain X-ray diffraction data at 2.7 Angstrom, belonged to the hexagonal symmetry group P65 in the unit-cell parameters of a=b=122.12, c=75.55 and alpha=beta=90 degree, gamma=120 degree. The Matthews coefficient was estimated to be 3.12 Angstrom3 Da-1, corresponding to solvent contents of 52.65.
  🖺 Full Text HTML: Purification, crystallization, and preliminary structural analysis of multivalent immunogenic effector protein-anchored SARS-CoV-2 RBD
• Virological characteristics of the SARS-CoV-2 XBB.1.5 variant -
  Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the F486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determined the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. The intrinsic pathogenicity of XBB.1.5 in hamsters is lower than that of XBB.1. Importantly, we found that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC expression. In vivo experiments using recombinant viruses revealed that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, these data suggest that the mutations in ORF8 and S could enhance spreading of XBB.1.5 in humans.
  🖺 Full Text HTML: Virological characteristics of the SARS-CoV-2 XBB.1.5 variant
• 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 {Delta}(1-209), that mediates genome packaging despite lacking the N-terminal RNA-binding domain and SR region. Here, we show that {Delta}(1-209) and viral RNA assemble into vRNPs that are remarkably similar in size and shape to those formed with full-length N protein. We show that assembly of {Delta}(1-209) vRNPs requires the leucine-rich helix (LH) of the central disordered region, and that the LH promotes N protein oligomerization. We also find that fusion of a phosphomimetic SR region to {Delta}(1-209) inhibits RNA binding and vRNP assembly. Our results provide new insights into the mechanisms by which RNA binding promotes N protein self-association and vRNP assembly, and how this process is modulated by SR phosphorylation.
  🖺 Full Text HTML: Assembly of SARS-CoV-2 ribonucleosomes by truncated N* variant of the nucleocapsid protein
• Molecular evolution and adaptation of SARS-CoV-2 omicron XBB sub-lineage Spike protein under African selection pressure. -
  The SARS-CoV-2 Omicron variant of concern (VOC) has multiple mutations in the spike (S) protein, which mediates viral infection and immunity. We analysed a sub lineage of Omicron, designated omicron XBB (XBB), that showed structural and functional changes in the S protein in response to the African selection pressures. We used molecular modelling to compare the S protein structures of the original Omicron and XBB found that XBB had a reduced receptor-binding domain (RBD) due to the loss of some {beta}-sheets, which may increase its affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. We also used Fast Unconstrained Bayesian AppRoximation (FUBAR) and Recombination Detection Program 4 (RDP 4) to perform selection and recombination analysis respectively of the S protein sequences of Omicron and XBB and detected signals of positive selection and recombination in the N terminal domain (NTD) of the S1 subunit, which contains antibody-binding epitopes, and the RBD, which is involved in viral entry. Our results reveal the structural and functional adaptation of the Omicron XBB variant in Africa and its potential implications for viral pathogenesis and immunity.
  🖺 Full Text HTML: Molecular evolution and adaptation of SARS-CoV-2 omicron XBB sub-lineage Spike protein under African selection pressure.
• Early estimation of life expectancy using weekly deaths data -

  This paper proposes a simple method to obtain early estimates of life expectancy at any age using data on weekly deaths. Although tailored on weekly deaths data from the Statistical Office of the European Union (Eurostat), the logic of the method is applicable to any timely data on infra-annual deaths counts, would they be quarterly, monthly, or other. When the method is applied to a time period still to complete, it is in substance a nowcasting technique whose reliability increases as new data become available, provided a correct specification of the model. It is also presented an application to 30 European countries for the years 2022 and 2023, returning a provisional estimate of life expectancy at birth much earlier than from official statistics. These early estimates show that in Europe the process of recovery in life expectancy at birth from the COVID-19 pandemic will be practically completed in 2023, unless unexpected mortality crises will occur in the second half of the year.

  🖺 Full Text HTML: Early estimation of life expectancy using weekly deaths data
• Mapping COVID-19 vaccine acceptance and uptake amongst Chinese residents: A systematic review and meta-analysis -

  Objective: Controlling the COVID-19 pandemic depends on the widespread acceptance of vaccination. Vaccine hesitancy is a growing area of concern in China. The aim of the study is to map the overall acceptance and uptake rates of COVID-19 vaccines across different groups.  Methods: Five peer-reviewed databases bases were searched (PubMed, EMBASE, Web of Science, EBSCO, and Scopus). Studies that conducted cross-sectional surveys in China to understand the acceptance/willingness to receive COVID-19 vaccines were included.  Results: Among 2420 identified studies, 47 studies with 327,046 participants were eligible for data extraction. Males had a higher uptake of COVID-19 vaccines (OR=1.17; 95% CI:1.08 - 1.27) along with Chinese residents with >= 5000 RMB monthly income (OR=1.08; 95% CI:1.02 - 1.14). Conclusion: COVID-19 vaccination uptake rates in China need to be improved. To inform public health decisions, continuous vaccination uptake monitoring is required.

  🖺 Full Text HTML: Mapping COVID-19 vaccine acceptance and uptake amongst Chinese residents: A systematic review and meta-analysis
• Effects of the COVID-19 pandemic on the restaurant industry: Comparisons between immigrants and US-born workers -
  The COVID-19 pandemic reduced employment in the U.S., across many industries. The restaurant industry was particularly hard hit, losing 2.5 million jobs in 2020 alone. Now in the recovery from the pandemic, the restaurant industry is experiencing an unprecedented shortage of workers, forcing many restaurants to raise their offered wages, reduce their hours of service, or close altogether. How have workers been affected by these demand shocks? Understanding the demand for restaurant workers during the pandemic and the recovery has important policy implications because restaurant workers make up the third largest occupation group and have the lowest wages of any occupation group. Foreign-born workers in particular are overrepresented in restaurants and in the back-of-house jobs that are lower paying and more dangerous. Using results from our nationally-representative survey of restaurant owners and hiring managers and our analysis of Community Population Survey data, we found that foreign-born workers fared worse than native-born workers as the restaurant industry shed jobs during the height of the pandemic. Our findings are consistent with previous studies suggesting that foreign-born workers are more vulnerable to negative business cycles than their native-born counterparts. But during the various stages of the recovery, when the restaurant industry experienced worker shortages, we also found that there was very little shifting toward foreign-born workers. These results are at odds with previous studies suggesting that foreign-born workers would be more attractive in these circumstances because they are more adaptable to changing labor demands (including dangerous working conditions like a pandemic) and do not have access to social safety net benefits like unemployment compensation. Part of the explanation for this surprising result may be found in recent, more restrictive immigration policies that have decreased the pool of available foreign-born workers.
  🖺 Full Text HTML: Effects of the COVID-19 pandemic on the restaurant industry: Comparisons between immigrants and US-born workers
• Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period -

  Background: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination. Methods: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression. Results: During September 22, 2020 - February 13, 2021, 2,712 eligible adults were enrolled, 1,541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model. Conclusion: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset.

  🖺 Full Text HTML: Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period
• The predictive and prognostic value of peripheral blood antigen-specific memory B cells in phospholipase A2 receptor-associated membranous nephropathy -

  Background Phospholipase A2 receptor-associated membranous nephropathy (PLA2R-MN) is an anti-PLA2R antibody (PLA2R-Ab) mediated autoimmune kidney disease. Although antibody titer correlates closely with disease activity, whether it can provide longer-term predictions on disease course and progression is unclear. Rituximab, a B-cell depletion therapy, has become the first-line treatment option for PLA2R-MN; however, the response to Rituximab varies among patients. Methods We developed a flow cytometry-based test that detects and quantifies PLA2R antigen-specific memory B cells (PLA2R-MBCs) in peripheral blood, the primary source for PLA2R-Ab production upon disease relapse. We applied the test to 159 blood samples collected from 28 patients with PLA2R-MN (at diagnosis, during and after immunosuppressive treatment, immunological remission, and relapse) to evaluate the relationship between circulating PLA2R-MBC levels and disease activity. Results The level of PLA2R-MBCs in healthy controls (n=56) is less than or equal to 1.5% of the total MBC compartment. High circulating PLA2R-MBC levels were detected in two patients post-Rituximab despite achieving immunologic and proteinuric remission, as well as in two patients with negative serum autoantibody but increasing proteinuria. Elimination of these cells with Rituximab improved clinical outcomes. Moreover, five patients exhibited elevated PLA2R-MBC levels before disease relapse, followed by a rapid decline to baseline when relapse became clinically evident. COVID-19 vaccination or SARS-CoV-2 infection significantly affected the dynamics of circulating PLA2R-MBCs. Conclusions This study suggests that monitoring PLA2R-MBC levels in patients with PLA2R-MN may help refine and individualize immunosuppressive therapy and predict disease course and progression. The technology and findings may also have broader applications in the clinical management of other autoimmune diseases.

  🖺 Full Text HTML: The predictive and prognostic value of peripheral blood antigen-specific memory B cells in phospholipase A2 receptor-associated membranous nephropathy
• Coronaviruses Spike glycoprotein endodomains: the sequence and structure-based comprehensive study -
  The flexibility of proteins makes them available to interact with many biomolecules in the cell. Specifically, such interactions in viruses help them to perform more functions despite having a smaller genome. Therefore, these flexible regions can be exciting and essential targets to be explored for their role in pathogenicity and therapeutic developments as they achieve essential interactions. In the continuation with our previous study on disordered analysis of SARS-CoV-2 spike cytoplasmic tail (CTR), or endodomain, here we have explored the disordered potential endodomains of six other coronaviruses using multiple bioinformatics approaches and molecular dynamics simulations. Based on the comprehensive analysis of its sequence and structural composition, we report the varying disorder propensity in endodomains of spike proteins of coronaviruses. The observations of this study may help to understand the importance of spike glycoprotein endodomain and creating therapeutic interventions against them.
  🖺 Full Text HTML: Coronaviruses Spike glycoprotein endodomains: the sequence and structure-based comprehensive study
• Predicting host-based, synthetic lethal antiviral targets from omics data -
  Traditional antiviral therapies often have limited effectiveness due to toxicity and development of drug resistance. Host-based antivirals, while an alternative, may lead to non-specific effects. Recent evidence shows that virus-infected cells can be selectively eliminated by targeting synthetic lethal (SL) partners of proteins disrupted by viral infection. Thus, we hypothesized that genes depleted in CRISPR KO screens of virus-infected cells may be enriched in SL partners of proteins altered by infection. To investigate this, we established a computational pipeline predicting SL drug targets of viral infections. First, we identified SARS-CoV-2-induced changes in gene products via a large compendium of omics data. Second, we identified SL partners for each altered gene product. Last, we screened CRISPR KO data for SL partners required for cell viability in infected cells. Despite differences in virus-induced alterations detected by various omics data, they share many predicted SL targets, with significant enrichment in CRISPR KO-depleted datasets. Comparing data from SARS-CoV-2 and influenza infections, we found possible broad-spectrum, host-based antiviral SL targets. This suggests that CRISPR KO data are replete with common antiviral targets due to their SL relationship with virus-altered states and that such targets can be revealed from analysis of omics datasets and SL predictions.
  🖺 Full Text HTML: Predicting host-based, synthetic lethal antiviral targets from omics data
• Evidence of Leaky Protection Following COVID-19 Vaccination and SARS-CoV-2 Infection in an Incarcerated Population -

  Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent (“leaky”) protection against infection remains unknown. We examined the effect of prior infection, vaccination, and hybrid immunity on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, cellblock, and no documented exposure to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection, vaccination, and hybrid immunity reduced the infection risk of residents without a documented exposure (HR: 0.36 [0.25-0.54]; 0.57 [0.42-0.78]; 0.24 [0.15-0.39]; respectively) and with cellblock exposures (0.61 [0.49-0.75]; 0.69 [0.58-0.83]; 0.41 [0.31-0.55]; respectively) but not with cell exposures (0.89 [0.58-1.35]; 0.96 [0.64-1.46]; 0.80 [0.46-1.39]; respectively). Associations were similar during the Delta period and when analyses were restricted to tested residents. Although associations may not have been thoroughly adjusted due to dataset limitations, the findings suggest that prior infection and vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in crowded settings.

  🖺 Full Text HTML: Evidence of Leaky Protection Following COVID-19 Vaccination and SARS-CoV-2 Infection in an Incarcerated Population

From Clinical Trials

• Study of Obeldesivir in Children and Adolescents With COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Obeldesivir
  Sponsor:   Gilead Sciences
  Not yet recruiting

• EFFECT OF COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19 - Condition:   Post-COVID-19 Syndrome
  Intervention:   Behavioral: rehacom
  Sponsor:   Cairo University
  Enrolling by invitation

• Immunogenicity and Safety of AdCLD-CoV19-1 OMI as a Booster: A COVID-19 Preventive Vaccine in Healthy Volunteers - Conditions:   COVID-19;   Vaccines
  Interventions:   Biological: AdCLD-CoV19-1 OMI;   Biological: Comirnaty Bivalent 0.1mg/mL (tozinameran and riltozinameran)
  Sponsor:   Cellid Co., Ltd.
  Not yet recruiting

• Using Text Messages to Boost COVID-19 Vaccine Booking Rate - Conditions:   Vaccination Hesitancy;   COVID-19
  Interventions:   Behavioral: Behavioural science-informed text messages;   Behavioral: Control
  Sponsors:   The Behavioural Insights Team;   Public Health England;   Department of Health and Social Care;   NHS England and NHS Improvement
  Completed

• Ivermectin to Prevent SARS-CoV-2 (COVID-19) Hospitalisation in Subjects Over 50 - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Drug: Ivermectin;   Drug: Placebo
  Sponsor:   Insud Pharma
  Terminated

• Methylprednisolone in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS) - Condition:   Post-COVID-19 Syndrome
  Intervention:   Drug: Methylprednisolone
  Sponsor:   Charite University, Berlin, Germany
  Not yet recruiting

• A Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19 - Conditions:   SARS CoV 2 Infection;   Influenza, Human
  Interventions:   Biological: BIMERVAX;   Biological: SIIV
  Sponsor:   Hipra Scientific, S.L.U
  Not yet recruiting

• Leveraging Community Health Workers to Combat COVID-19 and Mental Health Misinformation in Haiti, Malawi, and Rwanda - Conditions:   Mental Health;   COVID-19;   Misinformation
  Interventions:   Behavioral: Card-Sorting Activity (Pre-intervention design);   Behavioral: SMS Crafting (Pre-intervention design);   Behavioral: SMS Messaging
  Sponsors:   Harvard Medical School (HMS and HSDM);   Partners in Health
  Active, not recruiting

• A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Varients in Healthy Individuals - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Intervention:   Biological: BNT162b2 (Omi XBB.1.5)
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• Pulmonary Artery Pressure in COVID-19 Survivors - Condition:   Pulmonary Hypertension Secondary
  Intervention:   Diagnostic Test: right heart catheterization (RHC).
  Sponsor:   Mansoura University Hospital
  Enrolling by invitation

• Preliminary Efficacy of a Technology-based Physical Activity Intervention for Older Korean Adults During the COVID-19 Pandemic - Conditions:   Cardiovascular Health;   Physical Function
  Intervention:   Behavioral: Golden Circle
  Sponsor:   University of Illinois at Urbana-Champaign
  Completed

• Supported Employment COVID-19 Rapid Testing for PWID - Condition:   Health Behavior
  Intervention:   Behavioral: Supported Employment
  Sponsor:   University of Oregon
  Not yet recruiting

• Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19 - Condition:   Coronavirus Infections
  Interventions:   Drug: tixagevimab/cilgavimab 150+150 mg;   Drug: tixagevimab/cilgavimab 300+300 mg;   Drug: regdanvimab
  Sponsors:   City Clinical Hospital No.52 of Moscow Healthcare Department;   Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
  Active, not recruiting

• Playing Games to Learn About Children’s Vaccines Project - Conditions:   HPV;   COVID-19;   Vaccine-Preventable Diseases
  Intervention:   Behavioral: vaccination games
  Sponsor:   Michigan State University
  Recruiting

• Cereset Research Long-Term Healthcare Worker Study - Conditions:   Stress;   Anxiety;   Autonomic Dysregulation;   Acoustic Stimulation;   Hyperarousal;   Health Personnel
  Intervention:   Device: Cereset Research
  Sponsors:   Wake Forest University Health Sciences;   Susanne Marcus Collins Foundation, Inc.
  Not yet recruiting

From PubMed

• Alkyne as a Latent Warhead to Covalently Target SARS-CoV-2 Main Protease - There is an urgent need for improved therapy to better control the ongoing COVID-19 pandemic. The main protease M^(pro) plays a pivotal role in SARS-CoV-2 replications, thereby representing an attractive target for antiviral development. We seek to identify novel electrophilic warheads for efficient, covalent inhibition of M^(pro). By comparing the efficacy of a panel of warheads installed on a common scaffold against M^(pro), we discovered that the terminal alkyne could covalently modify…

• Discovery and Mechanism Study of SARS-CoV-2 3C-like Protease Inhibitors with a New Reactive Group - 3CL^(pro) is an attractive target for the treatment of COVID-19. Using the scaffold hopping strategy, we identified a potent inhibitor of 3CL^(pro) (3a) that contains a thiocyanate moiety as a novel warhead that can form a covalent bond with Cys145 of the protein. Tandem mass spectrometry (MS/MS) and X-ray crystallography confirmed the mechanism of covalent formation between 3a and the protein in its catalytic pocket. Moreover, several analogues of compound 3a were designed and synthesized….

• A Suitable Membrane Distance Regulated by the RBD_ACE2 Interaction is Critical for SARS-CoV-2 Spike-Mediated Viral Invasion - The receptor-binding domain (RBD) of spike recognizing the receptor angiotensin-converting enzyme 2 (ACE2) initiates membrane fusion between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cell membrane. Although the structure of the RBD_ACE2 complex has been well studied, its functional mechanism in membrane fusion is still not fully understood. Here, using an in vitro cell-vesicle content-mixing assay, it is found that the cleavage at the S2’ site by thrombin (Thr) protease…

• Endotheliopathy of liver sinusoidal endothelial cells in liver disease - Liver is the largest solid organ in the abdominal cavity, with sinusoid occupying about half of its volume. Under liver disease, hemodynamics in the liver tissue dynamically change, resulting in injury to liver sinusoidal endothelial cells (LSECs). We discuss the injury of LSECs in liver diseases in this article. Generally, in noninflamed tissues, vascular endothelial cells maintain quiescence of circulating leukocytes, and unnecessary blood clotting is inhibited by multiple antithrombotic…

• Convalescent plasma from Norwegian blood donors to treat COVID-19 - BACKGROUND: At the start of the pandemic, the Norwegian Directorate of Health and Norwegian blood banks initiated the production of COVID-19 convalescent plasma within the framework of clinical studies. In this article we describe the blood donors who participated.

• De novo design of bioactive phenol and chromone derivatives for inhibitors of Spike glycoprotein of SARS-CoV-2 in silico - This work presents the synthesis of 12 phenol and chromone derivatives, prepared by the analogs, and the possibility of conducting an in silico study of its derivatives as a therapeutic alternative to combat the SARS-CoV-2, pathogen responsible for COVID-19 pandemic, using its S-glycoprotein as a macromolecular target. After the initial screening for the ranking of the products, it was chosen which structure presented the best energy bond with the target. As a result, derivative 4 was submitted…

• Endothelial FoxM1 reactivates aging-impaired endothelial regeneration for vascular repair and resolution of inflammatory lung injury - Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS). Here, we demonstrated that persistent lung injury and high mortality in aged mice after sepsis challenge were attributable to impaired endothelial regeneration and vascular repair. Genetic lineage tracing study showed that endothelial regeneration after sepsis-induced vascular injury was mediated by lung resident endothelial proliferation in young adult mice, whereas this…

• Forodesine and Riboprine Exhibit Strong Anti-SARS-CoV-2 Repurposing Potential: In Silico and In Vitro Studies - Lately, nucleos(t)ide antivirals topped the scene as top options for the treatment of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Targeting the two broadly conserved SARS-CoV-2 enzymes, RNA-dependent RNA polymerase (RdRp) and 3’-to-5’ exoribonuclease (ExoN), together using only one shot is a very successful new tactic to stop SARS-CoV-2 multiplication irrespective of the SARS-CoV-2 variant type. Herein, the current…

• Anticancer pan-ErbB inhibitors reduce inflammation and tissue injury and exert broad-spectrum antiviral effects - Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib…

• Pyronaridine tetraphosphate is an efficacious antiviral and anti-inflammatory active against multiple highly pathogenic coronaviruses - The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to be one of the largest dangers to human health around the world. The need for effective antiviral and anti-inflammatory treatments is still extremely high as newly emerging variants threaten the efficacy of currently used treatment options. Many compounds are effective at inhibiting SARS-CoV-2 infection in vitro but fail to recapitulate that efficacy in vivo….

• Identification of Promising Sulfonamide Chalcones as Inhibitors of SARS-CoV-2 3CL^pro through Structure-Based Virtual Screening and Experimental Approaches - 3CL^(pro) is a viable target for developing antiviral therapies against the coronavirus. With the urgent need to find new possible inhibitors, a structure-based virtual screening approach was developed. This study recognized 75 pharmacologically bioactive compounds from our in-house library of 1052 natural product-based compounds that satisfied drug-likeness criteria and exhibited good bioavailability and membrane permeability. Among these compounds, three promising sulfonamide chalcones were…

• TGF-β1 inhibition of ACE2 mediated by miRNA uncovers novel mechanism of SARS-CoV-2 pathogenesis - SARS-CoV-2 utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin-converting enzyme 2 (ACE2). Decreased cell surface density of ACE2 contributes to mortality during COVID-19. Studies published early during the pandemic reported that people with cystic fibrosis (PwCF) treated with the high efficiency CFTR modulators ETI (elexacaftor-tezacaftor-ivacaftor) had higher ACE2 levels and milder COVID-19 symptoms, compared to people without CF. Subsequent studies did…

• WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by various disabling symptoms including exercise intolerance and is diagnosed in the absence of a specific cause, making its clinical management challenging. A better understanding of the molecular mechanism underlying this apparent bioenergetic deficiency state may reveal insights for developing targeted treatment strategies. We report that overexpression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3),…

• Endogenous and Therapeutic 25-hydroxycholesterols May Worsen Early SARS-CoV-2 Pathogenesis in Mice - Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-hydroxycholesterol (25HC), a product of activity of cholesterol-25-hydroxylase (CH25H) upon cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against SARS-CoV-2. However, 25HC can also amplify inflammation and be converted by CYP7B1 to 7α,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, using in vitro studies and two…

• Design of a bifunctional pan-sarbecovirus entry inhibitor targeting the cell receptor and viral fusion protein - Development of highly effective antivirals that are robust to viral evolution is a practical strategy for combating the continuously evolved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inspired by viral multistep entry process, we here focus on developing a bispecific SARS-CoV-2 entry inhibitor, which acts on the cell receptor angiotensin converting enzyme 2 (ACE2) and viral S2 fusion protein. First, we identified a panel of diverse spike (S) receptor-binding domains (RBDs) and…

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