Covid-19 Sentry

Contents

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

From Preprints

• The mathematics of the reproduction number R for Covid-19: A primer for demographers -
  The reproduction number R is a key indicator to monitor the dynamics of Covid-19 and to assess the effect of control strategies that frequently have high social and economic costs. Despite having an analog in demography’s “net reproduction rate” that has been routinely computed for a century, demographers may not be familiar with the concept and measurement of R in the context of Covid-19. This article intends to be a primer for understanding and estimating R in demography. We show that R can be estimated as a ratio between the numbers of new cases today divided by the weighted average of cases in previous days. We present two alternative derivations for these weights based on how risks change over time: constant vs. exponential decay. We provide estimates of these weights and demonstrate their use in calculating R to trace the course of the first pandemic year in several countries.
  🖺 Full Text HTML: The mathematics of the reproduction number R for Covid-19: A primer for demographers
• The COVID-19 pandemic and fertility decline in Costa Rica: A brief plunge due to psychosocial and economic factors and a baby bust driven by migration decisions -
  The national birth registry shows a substantial baby bust in 2021 – the first full year plus nine months into the COVID-19 pandemic. The fertility of native Costa Rican women dropped by 13%. This decrease did not deviate from pre-existing fertility trends. A brief plunge in conceptions during the first full month of the pandemic (April 2020) decreased the fertility rate in January 2021 by as much as 24% for some groups. This plunge was a response to the hardships caused by pandemic mitigation measures as well as uncertainties and fears concerning the novel disease rather than to the physiological harm of the disease itself. The 2021 decrease in births among immigrant women (who contribute one-fifth of the birth rate) was 78% larger than among native women, driven mostly by pandemic-induced migration decisions. The data hint at a pandemic baby boom in low-SES communities and, especially, in families with several children.
  🖺 Full Text HTML: The COVID-19 pandemic and fertility decline in Costa Rica: A brief plunge due to psychosocial and economic factors and a baby bust driven by migration decisions
• Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu -
  Viroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry (MS) in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for mechanisms of their biological functions as well as their potential as therapeutic targets.
  🖺 Full Text HTML: Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu
• Unraveling COVID-19: Descriptive Analytics in a Middle-Income Country, Paving the Path Forward -

  The outbreak of COVID-19 unleashed an unprecedented global pandemic, leaving a profound impact on lives and economies worldwide. Recognizing its severity, the World Health Organization swiftly declared it a public health emergency of international concern. Tragically, the Philippines reported the first death case outside China, leading to a surge in cases following the first instance of local transmission. In response to this crisis, collaborative efforts have been underway to control the disease and minimize its health and socio-economic impacts. The COVID-19 epidemic curve holds vital insights into the history of exposure, transmission, testing, tracing, social distancing measures, community lockdowns, quarantine, isolation, and treatment, offering a comprehensive perspective on the nation9s response. One approach to gaining crucial insights is through meticulous analysis of available datasets, empowering us to inform future strategies and responses effectively. This paper aims to provide descriptive data analytics of the COVID-19 pandemic in the Philippines, summarizing the country9s fight by visualizing epidemiological and mobility datasets, revisiting scientific papers and news articles, and creating a timeline of the key issues faced during the pandemic. By leveraging these multifaceted analyses, policymakers and health authorities can make informed decisions to enhance preparedness, expand inter-agency cooperation, and combat future public health crises effectively. This study seeks to serve as a valuable resource, guiding nations worldwide in comprehending and responding to the challenges posed by COVID-19 and beyond.

  🖺 Full Text HTML: Unraveling COVID-19: Descriptive Analytics in a Middle-Income Country, Paving the Path Forward
• Strategic use of SARS-CoV-2 wastewater concentration data could enhance, but not replace, high-resolution community prevalence survey programmes -

  Wastewater-based epidemiology (WBE) has been proposed as a tool for public health authorities to monitor community transmission of SARS-CoV-2 and other agents. Here, we review the utility of WBE for estimating SARS-CoV-2 prevalence using wastewater data from the Environmental Monitoring for Health Protection (EMHP) programme and prevalence data from the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. Our analysis shows a temporally evolving relationship between wastewater and prevalence which limits the utility of WBE for estimating SARS-CoV-2 prevalence in high spatial resolution without a concurrent prevalence survey. We further characterise WBE for SARS-CoV-2 prevalence as i) vaccination-coverage-dependent and ii) variant-specific. Our work provides a gesopatial framework to map wastewater concentrations to public health boundaries, enabling public health authorities to interpret the relationship between wastewater and prevalence. We demonstrate that WBE can improve the cost efficiency and accuracy of community prevalence surveys which on their own may have incomplete geographic coverage or small sample sizes.

  🖺 Full Text HTML: Strategic use of SARS-CoV-2 wastewater concentration data could enhance, but not replace, high-resolution community prevalence survey programmes
• Effect of Trait Anxiety and Quarantine on Mood and Decision Making -
  Our social environment influences our affective states and decisions, which was quite evident during COVID-19 pandemic-imposed quarantine. However, little is understood about recovery from social deprivation, especially for those with high trait anxiety. To understand this, we gathered ~24000 momentary assessments of affect and social interactions over three days of isolation followed by seven days of recovery from 116 young adults returning to a university campus. Quarantine induced a greater desire for social interactions and post-quarantine, individuals attempted to make up for this in different ways. High trait anxious individuals, who experienced more stressful events, higher negative affect, and lower positive affect during and after quarantine, depended more on interaction with people “close” to them. They derived greater emotional benefits from close interactions and experienced greater reductions in negative affect due to such positive events. However, low trait anxious individuals experienced less stress, and post-release, they interacted more with distant companions, which increased their positive affect. We also studied how affective states impacted decision-making through a virtual patch-foraging task played during and after quarantine. Affective states reported in the last 24 hours significantly impacted participants’ near-optimal strategies to maximize rewards in the task. Participants with high fluctuation in affective states tended to over-harvest, while those with high average negative affect tended to under-harvest. Our results highlight how social deprivation impacts affective states as a function of trait anxiety and social interactions and their effects on reward-based decision-making.
  🖺 Full Text HTML: Effect of Trait Anxiety and Quarantine on Mood and Decision Making
• 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

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

• Management of chronic myelogenous leukemia with COVID-19 and hepatitis B - The application of immunosuppressive agents and targeted drugs has opened a novel approach for the treatment of hematological tumors, and the application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia is one of the landmark breakthroughs that has considerably improved the prognosis of CML patients. However, with the extensive use of TKI, the co-infection of CML patients has become increasingly apparent, especially regarding infectious diseases such as hepatitis B and…

• Immunogenicity of BNT162b2 in children 6 months to under 5 years of age with previous SARS-CoV-2 infection, in the era of Omicron predominance - CONCLUSIONS: Children previously infected with SARS-CoV-2 Omicron variant, developed robust neutralizing antibody response against Omicron variant after single-dose BNT162b2. Children with an interval of > 6 months since COVID-19 infection developed higher neutralizing antibody response compared to those with a 3-to-6-month interval.

• Neutralizing antibody and T-cell responses against SARS-CoV-2 variants by heterologous CoronaVac/ChAdOx-1 vaccination in elderly subjects with chronic obstructive pulmonary disease - CONCLUSION: Heterologous CoVac/ChAd vaccine induced the production of NAb against SARS-CoV-2 WT, Alpha, Beta, and Delta variants, but low for Omicron in COPD patients. Induction of CD4 T-cell subset responses was slightly observed by this vaccine regimen.

• Cysteamine-mediated blockade of the glycine cleavage system modulates epithelial cell inflammatory and innate immune responses to viral infection - Transient blockade of glycine decarboxylase (GLDC) can restrict de novo pyrimidine synthesis, which is a well-described strategy for enhancing the host interferon response to viral infection and a target pathway for some licenced anti-inflammatory therapies. The aminothiol, cysteamine, is produced endogenously during the metabolism of coenzyme A, and is currently being investigated in a clinical trial as an intervention in community acquired pneumonia resulting from viral (influenza and…

• Bioengineered Neutrophil Extinguisher Targets Cascade Immune Pathways of Macrophages for Alleviating Cytokine Storm in Pneumonia - Cytokine storm is a common complication of COVID-19 pneumonia and has been proven to contribute to high mortality rates. However, current treatment approaches exhibit limited potential to balance immune response and overproduction of inflammatory cytokines, leading to poor therapeutic outcomes. Herein, a smart bioengineered neutrophil, Extinguisher, composed of live neutrophils encapsulating the liposome formulation of NF-κB suppressor MLN4924 and STING inhibitor H-151 (Lip@MH), is developed for…

• Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 That Exhibits Antiviral Efficacy in SARS-CoV-2-Infected African Green Monkeys - Remdesivir 1 is an phosphoramidate prodrug that releases the monophosphate of nucleoside GS-441524 (2) into lung cells, thereby forming the bioactive triphosphate 2-NTP. 2-NTP, an analog of ATP, inhibits the SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription of viral RNA. Strong clinical results for 1 have prompted interest in oral approaches to generate 2-NTP. Here, we describe the discovery of a 5’-isobutyryl ester prodrug of 2 (GS-5245, Obeldesivir, 3) that has low cellular…

• Novel mono- and multivalent N-acetylneuraminic acid glycoclusters as potential broad-spectrum entry inhibitors for influenza and coronavirus infection - N-acetylneuraminic acid (Neu5Ac) is a glycan receptor of viruses spread in many eukaryotic cells. The present work aimed to design, synthesis and biological evaluation of a panel of Neu5Ac derivatives based on a cyclodextrin (CD) scaffold for targeting influenza and coronavirus membrane proteins. The multivalent Neu5Ac glycoclusters efficiently inhibited chicken erythrocyte agglutination induced by intact influenza virus in a Neu5Ac density-dependent fashion. Compared with inhibition by Neu5Ac,…

• Post-COVID-19 syndrome management: Utilizing the potential of dietary polysaccharides - The COVID-19 pandemic has caused significant global impact, resulting in long-term health effects for many individuals. As more patients recover, there is a growing need to identify effective management strategies for ongoing health concerns, such as post-COVID-19 syndrome, characterized by persistent symptoms or complications beyond several weeks or months from the onset of symptoms. In this review, we explore the potential of dietary polysaccharides as a promising approach to managing…

• 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….

• Hypomethylated interferon regulatory factor 8 recruits activating protein-2α to attenuate porcine epidemic diarrhea virus infection in porcine jejunum - Interferon regulatory factor 8 (IRF8) is a key regulator of innate immune receptor signaling that resists pathogen invasion by regulating cell growth and differentiation. Porcine epidemic diarrhea virus (PEDV) targets the intestine and damages the mucosal barrier. However, whether IRF8 regulates PEDV replication remains unclear. We revealed that PEDV infection activated IRF8 expression. Moreover, IRF8 deletion drastically promoted PEDV replication and invasion, increasing the virus copies and…

• 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…

From Patent Search