Covid-19 Sentry

Contents

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

From Preprints

• Preprints and Pandemics: Interventions into the Dynamic System of Scholarly Communication -
  The COVID-19 pandemic is an exemplar of how scholarly communication can change in response to external shocks, even as the scholarly knowledge ecosystem is evolving rapidly, and many argue that swift and fundamental interventions are needed. However, it is much easier to identify ongoing changes and emerging interventions than to understand their immediate and long term impacts. This is illustrated by comparing the approaches applied by the scientific community to understand public health risks and interventions with those applied by the scholarly communications community to the science of COVID-19. There are substantial disagreements over the short- and long- term benefits of most proposed approaches to changing the practice of science communication, and the lack of systematic, empirically-based research in this area makes these controversies difficult to resolve. We argue that the methodology of analysis and intervention developed within public health can be usefully applied to the science-of-science. Starting with the history of DDT application, we illustrate four ways complex human systems threaten reliable predictions and blunt ad-hoc interventions. We then show how these four threats apply lead to the last major intervention in scholarly publication – the article publishing charge based open access model – to yield surprising results. Finally, we outline how these four threats may affect the impact of preprint initiatives, and we identify approaches drawn from public health to mitigate these threats.
  🖺 Full Text HTML: Preprints and Pandemics: Interventions into the Dynamic System of Scholarly Communication
• The psychological mechanism of internet information processing for post-treatment evaluation. Heliyon, 8 (5), E09351 -
  Digital healthcare has been greatly benefiting the public health system, especially during the COVID-19 pandemic. In digital healthcare, information communication through the Internet is crucial. The current study explores how patients’ accessibility and trust in Internet information influence their decisions and ex-post assessment of healthcare providers by employing the Bayesian Mindsponge Framework (BMF) on a dataset of 1,459 Vietnamese patients. We find that patients’ accessibility to Internet information positively affects the perceived sufficiency of information for choosing a healthcare provider, and their trust in the information intensifies this effect. Internet information accessibility is negatively associated with post-treatment assessment of healthcare providers, and trust also moderates this effect. Moreover, patients considering professional reputation important while making a decision are more likely to regard their choices as optimal, whereas patients considering services important have contradicting tendencies. Based on these findings, a concern about the risk of eroding trust toward Internet sources about healthcare information is raised. Thus, quality control and public trust-building measures need to be taken to improve the effectiveness of healthcare-related communication through the Internet and facilitate the implementation of digital healthcare.
  🖺 Full Text HTML: The psychological mechanism of internet information processing for post-treatment evaluation. Heliyon, 8 (5), E09351
• Comparing Waves of COVID-19 in the US: Scale of response changes over time -

  Local response to the SARS-CoV-2 pandemic differed spatially across the United States but the drivers of this spatial variation remain unclear. We approach this open question by studying the relationship between the growth rate of subsequent waves of the pandemic at the county level during the first year of the pandemic, asking whether state or county demographics better explain variation in this relationship. We found clear spatiotemporal patterns in the relationship between the slopes of subsequent waves in a given county. Generally the standardized difference between the growth rates of waves 1 and 2 and waves 2 and 3 were strongly positively correlated over short distances and shifted to a weak negative correlation at intermediate distances. We also found that peer county health group (a categorization of counties by demographic information relevant to public health) explained variation in response better between wave 1 and 2, while state identity was most important between wave 2 and 3. Taken together, we suggest that there are identifiable spatial patterns in pandemic response across the US but that the nature of these patterns change over the course of the pandemic.

  🖺 Full Text HTML: Comparing Waves of COVID-19 in the US: Scale of response changes over time
• Modelling the impact of rapid tests, tracing and distancing in lower-income countries suggest that optimal policies vary with rural-urban settings -

  Low- and middle-income countries (LMICs) remain of high potential for hotspots for COVID-19 deaths and emerging variants given the inequality of vaccine distribution and their vulnerable healthcare systems. We aim to evaluate containment strategies that are sustainable and effective for LMICs. We constructed synthetic populations with varying contact and household structures to capture LMIC demographic characteristics that vary across communities. Using an agent-based model, we explored the optimal containment strategies for rural and urban communities by designing and simulating setting-specific strategies that deploy rapid diagnostic tests, symptom screening, contact tracing and physical distancing. In low-density rural communities, we found implementing either high quality (sensitivity > 50%) antigen rapid diagnostic tests or moderate physical distancing could contain the transmission. In urban communities, we demonstrated that both physical distancing and case finding are essential for containing COVID-19 (average infection rate < 10%). In high density communities that resemble slums and squatter settlements, physical distancing is less effective compared to rural and urban communities. Lastly, we demonstrated contact tracing is essential for effective containment. Our findings suggested that rapid diagnostic tests could be prioritised for control and monitor COVID-19 transmission and highlighted that contact survey data could guide strategy design to save resources for LMICs. An accompanying open source R package is available for simulating COVID-19 transmission based on contact network models.

  🖺 Full Text HTML: Modelling the impact of rapid tests, tracing and distancing in lower-income countries suggest that optimal policies vary with rural-urban settings
• Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19 -
  Social isolation is a relevant problem for veterans who are at risk for disengaging from others as a function of transition stress from military life to civilian life, and given high rates of exposure to trauma and psychological distress. Few researchers have examined social isolation in veterans over time, particularly during COVID-19 that led to significant barriers and restrictions on social interactions. The purpose of this longitudinal study was to assess veterans’ experience of social isolation and its mental health and social functioning correlates during a 6-month period of the COVID-19 pandemic. Participants were 188 United States veterans of the Iraq and Afghanistan wars, who completed a total of four assessments: one every two months for a total duration of six months. Surveys included measures of global mental health and social functioning as indicated by perceived emotional support, quality of marriage, and couple satisfaction. Multilevel modeling was used to assess 1) growth models to determine whether social isolation changed over time and the trajectory of that change (i.e., linear or quadratic); and 2) whether social isolation was related to both concurrent and prospective indicators of mental health and social functioning. All analyses included person mean centered and grand mean centered isolation to assess for within-and between-person effects. Veterans reported a quadratic trajectory in social isolation that decreased slightly and stabilized over time. Findings indicate that higher social isolation, at both the within- and between-person level, was negatively associated with concurrent emotional support, mental health, quality of marriage, and couple satisfaction. However, all prospective effects were nonsignificant at the within-person level. Results suggest although isolation may decrease over time, veterans report worse mental health and social functioning during times when they report higher levels of social isolation compared to themselves and others. Future work is needed to determine if interventions can be applied during those times to prevent or target those negative associations.
  🖺 Full Text HTML: Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19
• A clinical stage LMW-DS drug inhibits cell infection by coronaviruses and modulates reactive cytokine release from microglia -
  Most coronaviruses infect animals including bats, birds and mammals, which act as hosts and reservoirs for the viruses, but the viruses can sometimes move host species and infect humans. Coronoviruses were first identified as human pathogens in the 1960s and now there are seven types known to infect humans. Whilst four of these types cause mild-to-moderate respiratory disease, the other three may cause more severe and possibly even fatal disease in vulnerable individuals particularly, with the most recent SARS-CoV-2 pandemic being associated with severe acute respiratory syndrome (SARS) in many infected people. The aim of the present study was to evaluate the potential of a unique low molecular weight dextran sulphate (LMW-DS) clinical stage drug, ILB(R), to inhibit infection of human cells by the NL63 coronavirus assessed by immunofluorescence of viral particles, and also to see if the drug directly blocked the interaction of the SARS-CoV-2 viral spike protein with the ACE2 receptor. Furthermore, we evaluated if ILB(R) could modulate the downstream consequences of viral infection including the reactive cytokine release from human microglia induced by various SARS-CoV-2 variant spike proteins. We demonstrated that ILB(R) blocked ACE2:spike protein interaction and inhibited coronaviral infection. ILB(R) also attenuated the omicron-induced release of pro-inflammatory cytokines, including TNF, from human microglia, indicating control of post-viral neuroinflammation. In conclusion, given the safety profile of ILB(R) established in a number of Phase I and Phase II clinical trials, these results highlight the potential of ILB(R) to treat patients infected with coronaviruses to both limit infectivity and attenuate the progression to severe disease. There is now an opportunity to translate these findings quickly by the clinical investigation of drug efficacy.
  🖺 Full Text HTML: A clinical stage LMW-DS drug inhibits cell infection by coronaviruses and modulates reactive cytokine release from microglia
• MultiOMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells -
  Despite the availability of vaccines and approved therapeutics, the COVID-19 pandemic continues to rise owing to the emergence of newer variants. Several multi-omics studies have made available extensive evidence on host-pathogen interactions and potential therapeutic targets. Nonetheless, an increased understanding of host signaling networks regulated by post-translational modifications and their ensuing effect on the biochemical and cellular dynamics is critical to expanding the current knowledge on the host response to SARS-CoV-2 infections. Here, employing unbiased global transcriptomics, proteomics, acetylomics, phosphoproteomics, and exometabolome analysis of a lung-derived human cell line, we show that SARS-CoV-2 Norway/Trondheim-S15 strain induces time-dependent alterations in the induction of type I IFN response, activation of DNA damage response, dysregulated Hippo signaling, among others. We provide evidence for the interplay of phosphorylation and acetylation dynamics on host proteins and its effect on the altered release of metabolites, especially organic acids and ketone bodies. Together, our findings serve as a resource of potential targets that can aid in designing novel host-directed therapeutic strategies.
  🖺 Full Text HTML: MultiOMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells
• The Intestinal Microbiome, Dietary Habits, and Physical and Psychological Resilience in Postpartum Women -
  The population of postpartum women suffering from mental illness is increasing steadily, particularly under conditions of the COVID-19 pandemic. Identifying factors that contribute to resilience in postpartum women is urgently needed to decrease risks of poor physical and psychological functioning. Studies have linked variations in the intestinal microbiota to depression in clinical samples, but the impacts in postpartum women in a Japanese population are unknown. We conducted two studies to examine the links between intestinal microbiota, physical condition, and psychological state in nonclinical, postpartum Japanese women. Our results show that decreasing Lachnospira and alpha diversity of microbiome is related to high mental health risk (i.e., parenting stress and/or depression). Psychological resilience and physical conditions were associated with relative abundances of genera Blautia, Clostridium, Eggerthella. This study contributes to further understanding of the gut-brain axis mechanisms and supports proposals for interventions to enhance resilience in postpartum women.
  🖺 Full Text HTML: The Intestinal Microbiome, Dietary Habits, and Physical and Psychological Resilience in Postpartum Women
• A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile -
  Cellular immune defects associated with suboptimal responses to SARS-CoV-2 mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyzed antibody, B cell, CD4+ and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CI). The first two doses elicit weaker B cell and CD8+ T cell responses in HD than in CI, while CD4+ T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8+ T cell responses and enhances comparatively more Thelper (TH) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of TH cells in HD (TNF/IL-2 skewing), while others (CCR6, CXCR6, PD-1 and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieve robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure.
  🖺 Full Text HTML: A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile
• Future COVID-19 surges prediction based on SARS-CoV-2 mutations surveillance -
  COVID-19 has aptly revealed that airborne viruses such as SARS-CoV-2 with the ability to rapidly mutate, combined with high rates of transmission and fatality can cause a deadly world-wide pandemic in a matter of weeks. Apart from vaccines and post-infection treatment options, strategies for preparedness will be vital in responding to the current and future pandemics. Therefore, there is wide interest in approaches that allow predictions of increase in infections (surges) before they occur. We describe here real time genomic surveillance particularly based on mutation analysis, of viral proteins as a methodology for a priori determination of surge in number of infection cases. The full results are available for SARS-CoV-2 at http://pandemics.okstate.edu/covid19/, and are updated daily as new virus sequences become available. This approach is generic and will also be applicable to other pathogens.
  🖺 Full Text HTML: Future COVID-19 surges prediction based on SARS-CoV-2 mutations surveillance
• Immunogenicity and Protective Efficacy of a SARS-CoV-2 mRNA Vaccine Encoding Secreted Non-Stabilized Spike Protein in Mice -
  Establishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Here, we describe the preclinical studies of a SARS-CoV-2 mRNA encoding prefusion-unstabilized ectodomain spike protein encapsulated in lipid nanoparticles (LNP) “ChulaCov19”. In BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 g given 2 doses, 21 days apart, elicited robust neutralizing antibody (NAb) and T cells responses in a dose-dependent relationship. The geometric mean titer (GMT) of micro-virus neutralizing (micro-VNT) antibody against wild-type virus was 1,280, 11,762, 54,047, and 62,084, respectively. Higher doses induced better cross-neutralizing antibody against Delta and Omicron variants. This elicited specific immunogenicity was significantly higher than those induced by homologous prime-boost with inactivated (CoronaVac) or viral vector (AZD1222) vaccine. In heterologous prime-boost study, mice primed with either CoronaVac or AZD1222 vaccine and boosted with 5 g ChulaCov19 generated NAb 7-fold higher against wild-type virus (WT) and was also significantly higher against Omicron (BA.1 and BA.4/5) than homologous CoronaVac or AZD1222 vaccination. AZD1222-prime/mRNA-boost had mean spike-specific IFN-{gamma} positive T cells of 3,725 SFC/106 splenocytes, which was significantly higher than all groups except homologous ChulaCov19. Challenge study in human-ACE-2-expressing transgenic mice showed that ChulaCov19 at 1 g or 10 g protected mice from COVID-19 symptoms, prevented SARS-CoV-2 viremia, significantly reduced tissue viral load in nasal turbinate, brain, and lung tissues 99.9-100%, and without anamnestic of Ab response which indicated its protective efficacy. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or a boost vaccination and has entered clinical development.
  🖺 Full Text HTML: Immunogenicity and Protective Efficacy of a SARS-CoV-2 mRNA Vaccine Encoding Secreted Non-Stabilized Spike Protein in Mice
• Correcting COVID-19 Vaccine Misinformation in Ten Countries -
  What can be done to reduce misperceptions about COVID-19 vaccines? We present results from experiments conducted simultaneously on YouGov samples in ten countries (N = 10,600), which reveal that factual corrections consistently reduce false belief about the vaccines. Globally, exposure to corrections increases belief accuracy by .16 on a 4-point scale, while exposure to misinformation decreases belief accuracy by .09 on the same scale. Neither misinformation nor factual corrections affect intent-to-vaccinate or vaccine attitudes. We find modest evidence that the effects of fact-checks endure, with 39% of the original correction effect in the direction of greater accuracy still detectable two weeks after initial exposure. These findings illustrate both the possibilities and limitations of factual corrections. Across ten highly diverse populations, exposure to factual information reliably reduces belief in falsehoods about vaccines, but has minimal influence on subsequent behaviors and attitudes.
  🖺 Full Text HTML: Correcting COVID-19 Vaccine Misinformation in Ten Countries
• Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual. -

  Prolonged infections in immunocompromised individuals may be a source for novel SARS-CoV-2 variants, particularly when both the immune system and antiviral therapy fail to clear the infection, thereby promoting adaptation. Here we describe an approximately 16-month case of SARS-CoV-2 infection in an immunocompromised individual. Following monotherapy with the monoclonal antibody Bamlanivimab, the individual9s virus was resistant to this antibody via a globally unique Spike amino acid variant (E484T) that evolved from E484A earlier in infection. With the emergence and spread of the Omicron Variant of Concern, which also contains Spike E484A, E484T may arise again as an antibody-resistant derivative of E484A.

  🖺 Full Text HTML: Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual.
• Regional correlations of COVID-19 in Spain -
  This paper analyzes the correlation between confirmed cases of COVID-19 and several geographic, meteorological and socioeconomic variables at the province level in Spain. The results indicate that there is a strong and robust negative relationship between average temperature and the rate of cases of COVID-19. The explanatory power of other geographic and socioeconomic variables is much lower. A parsimonious model including population density and temperature is able to explain 67% of variation in cases of COVID. However, the results are inconclusive regarding the existence of a relationship between changes in temperature and changes in COVID cases, casting doubts on the existence of a negative link between temperature and the spread of the virus.
  🖺 Full Text HTML: Regional correlations of COVID-19 in Spain
• Health System Resilience-enhancing Strategies for Managing Public Health Emergencies of International Concerns (PHEIC): Success and Challenges. A Systematic Review Protocol -

  Introduction Health system resilience is the ability to prepare, manage, and learn from a sudden and unpredictable extreme change which impacts health systems. Health systems globally have recently been affected by a number of catastrophic events, including natural disasters, and infectious disease epidemics. Understanding health system resilience has never been more essential until emerging global pandemics. Therefore, the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic. Methods The systematic review will be reported using the Preferred reporting items for systematic review and meta-analysis protocols guideline (PRISMA-P). Reporting data on health system building blocks and systematic searches on resilience enhancing strategies for the management of Public Health Emergencies of International Concerns (PHEIC) after the establishment of International Health Regulations (IHR) since managing PHEIC after the establishment of IHR in 2007 will be included. The search will be conducted in PubMed, Scopus, Web of Science, and Google Scholar. Discussion Health system resilience is key to coping with catastrophic events, such as the economic crisis and COVID-19 pandemic. The mapping of available literature towards the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic to improve the level of preparedness and response to similar public health emergencies in the future. Conclusion A protocol for a global review of health system resilience for pandemic management is described. This review will add to the body of knowledge about health systems enhancing research and policy formulation.

  🖺 Full Text HTML: Health System Resilience-enhancing Strategies for Managing Public Health Emergencies of International Concerns (PHEIC): Success and Challenges. A Systematic Review Protocol

From Clinical Trials

• Booster Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Interventions:   Biological: SARS-CoV-2 subunit protein recombinant vaccine;   Biological: Active Comparator
  Sponsors:   PT Bio Farma;   Faculty of Medicine Universitas Padjadjaran;   Faculty of Medicine Universitas Udayana
  Recruiting

• A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine SCTV01E-1 in Population Aged Above 18 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E-1 on D0;   Biological: SCTV01E-1 on D28;   Biological: SCTV01E-1 on D150;   Biological: SCTV01E on D0;   Biological: SCTV01E on D28;   Biological: SCTV01E on D150;   Biological: SCTV01E-1 on D120;   Biological: SCTV01E on D120
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Novel Parameter LIT/N That Predicts Survival in COVID-19 ICU Patients - Condition:   COVID-19 Pneumonia
  Intervention:   Diagnostic Test: the LIT test
  Sponsors:   Gazi University;   Oxford MediStress
  Completed

• Efficacy and Safety of ES16001 in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ES16001 40 mg;   Drug: ES16001 80 mg;   Drug: ES16001 160 mg;   Drug: Placebo
  Sponsor:   Genencell Co. Ltd.
  Recruiting

• Multidisciplinary Day-hospital Versus Waiting List Management of Post-COVID-19 Persistent Symptoms (ECHAP-COVID) - Condition:   Post COVID-19 Condition
  Intervention:   Behavioral: Personalized multidisciplinary day-hospital intervention
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Efficacy and Safety Evaluation of Paxlovid for COVID-19: a Real-world Case-control Study - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: standard-of-care plus Paxlovid;   Drug: standard-of-care
  Sponsor:   Ruijin Hospital
  Recruiting

• The Impact of a Web-based Psychoeducation Programme With a Motivational AI Chatbot on Covid-19 Vaccine Hesitancy - Conditions:   Vaccine Hesitancy;   COVID-19
  Interventions:   Behavioral: AI-driven Vaccine Communicator;   Behavioral: Self-learning of COVID-19 vaccine knowledge
  Sponsor:   The Hong Kong Polytechnic University
  Not yet recruiting

• CArdiac REhabilitation for Building Exertional heArt Rate for Chronotropic Incompetence in Long COVID-19 - Conditions:   Long COVID;   COVID-19
  Intervention:   Behavioral: Cardiac Rehabilitation
  Sponsor:   University of California, San Francisco
  Not yet recruiting

• COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study - Conditions:   COVID-19;   Kidney Transplant
  Intervention:   Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   PPD;   Johns Hopkins University;   Sanofi Pasteur, a Sanofi Company
  Not yet recruiting

• HRQOL of Life After ECMO Due to COVID-19. - Conditions:   ARDS;   COVID-19 Pneumonia;   Extracorporeal Membrane Oxygenation
  Intervention:   Other: Phone Interview
  Sponsor:   Medical University of Vienna
  Recruiting

• Safety and Immunogenicity of COVID-19 Vaccine, AdCLD-CoV19-1 - Conditions:   COVID-19;   Vaccines
  Intervention:   Biological: AdCLD-CoV19-1
  Sponsors:   International Vaccine Institute;   Cellid Co., Ltd.
  Not yet recruiting

• Smartphone Intervention for Overdose and COVID-19 - Conditions:   Substance Use Disorders;   Overdose;   COVID-19
  Intervention:   Device: iThrive WI Intervention
  Sponsors:   University of Wisconsin, Madison;   National Institute on Drug Abuse (NIDA)
  Not yet recruiting

• Phase One Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of MSP008-22 in Healthy Adult Volunteers - Condition:   COVID-19
  Interventions:   Drug: MSP008-22;   Other: Placebo
  Sponsor:   Godavari Biorefineries Limited
  Not yet recruiting

• A Study to Evaluate the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine - Conditions:   COVID-19;   Influenza
  Interventions:   Drug: CIC Vaccine;   Drug: qNIV Vaccine;   Drug: SARS-CoV-2 rS Vaccine;   Drug: Influenza Vaccine
  Sponsor:   Novavax
  Not yet recruiting

• Self-proning and Repositioning in COVID-19 Outpatients at Risk of Complicated Illness - Conditions:   COVID-19;   COVID-19 Pneumonia;   Proning;   Hospitalization;   Death;   Outpatient;   Complication
  Intervention:   Other: Self-proning
  Sponsors:   Unity Health Toronto;   Applied Health Research Centre
  Recruiting

From PubMed

• BDA-410 inhibits SARS-CoV-2 main protease activity and viral replication in mammalian cells - No abstract

• The SARS-CoV-2 envelope protein disrupts barrier function in an in vitro human blood-brain barrier model - Patients with coronavirus disease 2019 (COVID-19) have been frequently reported to exhibit neurological manifestations and disruption of the blood-brain barrier (BBB). Among the risk factors for BBB breakdown, the loss of endothelial cells and pericytes has caused widespread concern. Recent studies have revealed that severe acute respiratory syndrome coronavirus 2 envelope (S2E) protein caused cell death. We tested the hypothesis that the S2E protein alone could induce BBB dysfunction. The S2E…

• Differential effect of SARS-CoV-2 infection on stress granule formation in Vero and Calu-3 cells - Stress granule formation is induced by numerous environmental stressors, including sodium arsenite treatment and viral infection. Accordingly, stress granules can inhibit viral propagation and function as part of the antiviral host response to numerous viral infections. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antagonizes stress granule formation, in part, via interaction between SARS-CoV-2 nucleocapsid (N) protein and Ras-GTPase-activating SH3-domain-binding protein 1…

• Dexamethasone, but Not Vitamin D or A, Dampens the Inflammatory Neutrophil Response to Protect At-risk COVID-19 Patients - Dexamethasone (DEX) was the first drug shown to save lives of critically ill coronavirus disease 2019 (COVID-19) patients suffering from respiratory distress. A hyperactivated state of neutrophils was found in COVID-19 patients compared to non-COVID pneumonia cases. Given the beneficial effects of DEX in COVID-19 patients, we investigated the effects of DEX and of other immunomodulatory drugs vitamin D3 (VD3) and retinoic acid (RA) on neutrophil function. DEX, but not VD3 or RA, significantly…

• Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by lactoferricin - In addition to vaccines, there is an urgent need for supplemental antiviral therapeutics to dampen the persistent COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The transmembrane protease serine 2 (TMPRSS2), that is responsible for proteolytic priming of the SARS-CoV-2 spike protein, appears as a rational therapeutic target. Accordingly, selective inhibitors of TMPRSS2 represent potential tools for prevention and treatment of COVID-19. Previously,…

• New Chemicals Suppressing SARS-CoV-2 Replication in Cell Culture - Candidates to being inhibitors of the main protease (Mpro) of SARS-CoV-2 were selected from the database of Voronezh State University using molecular modeling. The database contained approximately 19,000 compounds represented by more than 41,000 ligand conformers. These ligands were docked into Mpro using the SOL docking program. For one thousand ligands with best values of the SOL score, the protein-ligand binding enthalpy was calculated by the PM7 quantum-chemical method with the COSMO solvent…

• Dual Inhibition of HIV-1 and Cathepsin L Proteases by Sarcandra glabra - The COVID-19 pandemic continues to impose a huge threat on human health due to rapid viral mutations. Thus, it is imperative to develop more potent antivirals with both prophylactic and treatment functions. In this study, we screened for potential antiviral compounds from Sarcandra glabra (SG) against Cathepsin L and HIV-1 proteases. A FRET assay was applied to investigate the inhibitory effects and UPLC-HRMS was employed to identify and quantify the bioactive components. Furthermore, molecular…

• Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2 - The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a pandemic and has inflicted enormous damage on the lives of the people and economy of many countries worldwide. However, therapeutic agents against SARS-CoV-2 remain unclear. SARS-CoV-2 has a spike protein (S protein), and cleavage of the S protein is essential for viral entry. Nattokinase is produced by Bacillus subtilis var. natto and is beneficial to human health….

• Impact of Clarified Apple Juices with Different Processing Methods on Gut Microbiota and Metabolomics of Rats - The consumption of processed foods has increased compared to that of fresh foods in recent years, especially due to the coronavirus disease 2019 pandemic. Here, we evaluated the health effects of clarified apple juices (CAJs, devoid of pectin and additives) processed to different degrees, including not-from-concentrate (NFC) and from-concentrate (FC) CAJs. A 56-day experiment including a juice-switch after 28 days was designed. An integrated analysis of 16S rRNA sequencing and untargeted…

• Antiviral Activity of N₁,N₃-Disubstituted Uracil Derivatives against SARS-CoV-2 Variants of Concern - Despite the widespread use of the COVID-19 vaccines, the search for effective antiviral drugs for the treatment of patients infected with SARS-CoV-2 is still relevant. Genetic variability leads to the continued circulation of new variants of concern (VOC). There is a significant decrease in the effectiveness of antibody-based therapy, which raises concerns about the development of new antiviral drugs with a high spectrum of activity against VOCs. We synthesized new analogs of uracil derivatives…

• Anti-Inflammatory Activity of CIGB-258 against Acute Toxicity of Carboxymethyllysine in Paralyzed Zebrafish via Enhancement of High-Density Lipoproteins Stability and Functionality - Background: Hyperinflammation is frequently associated with the chronic pain of autoimmune disease and the acute death of coronavirus disease (COVID-19) via a severe cytokine cascade. CIGB-258 (Jusvinza^(®)), an altered peptide ligand with 3 kDa from heat shock protein 60 (HSP60), inhibits the systemic inflammation and cytokine storm, but the precise mechanism is still unknown. Objective: The protective effect of CIGB-258 against inflammatory stress of N-ε-carboxymethyllysine (CML) was tested to…

• Targeting the SARS-CoV-2 HR1 with Small Molecules as Inhibitors of the Fusion Process - The rapid and global propagation of the novel human coronavirus that causes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of this virus. In this paper, we studied the spike protein S2 domain of SARS-CoV-2 as it is the most conserved component and controls the crucial fusion process of SARS-CoV-2 as a target for different databases of small organic compounds. Our in silico methodology, based on…

• Autophagy Dysregulation in Metabolic Associated Fatty Liver Disease: A New Therapeutic Target - Metabolic associated fatty liver disease (MAFLD) is one of the most common causes of chronic liver disease worldwide. To date, there is no FDA-approved treatment, so there is an urgent need to determine its pathophysiology and underlying molecular mechanisms. Autophagy is a lysosomal degradation pathway that removes damaged organelles and misfolded proteins after cell injury through endoplasmic reticulum stress or starvation, which inhibits apoptosis and promotes cell survival. Recent studies…

• The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism? - Ritonavir is the most potent cytochrome P450 (CYP) 3A4 inhibitor in clinical use and is often applied as a booster for drugs with low oral bioavailability due to CYP3A4-mediated biotransformation, as in the treatment of HIV (e.g., lopinavir/ritonavir) and more recently COVID-19 (Paxlovid or nirmatrelvir/ritonavir). Despite its clinical importance, the exact mechanism of ritonavir-mediated CYP3A4 inactivation is still not fully understood. Nonetheless, ritonavir is clearly a potent…

• Heparan Sulfate and Sialic Acid in Viral Attachment: Two Sides of the Same Coin? - Sialic acids and heparan sulfates make up the outermost part of the cell membrane and the extracellular matrix. Both structures are characterized by being negatively charged, serving as receptors for various pathogens, and are highly expressed in the respiratory and digestive tracts. Numerous viruses use heparan sulfates as receptors to infect cells; in this group are HSV, HPV, and SARS-CoV-2. Other viruses require the cell to express sialic acids, as is the case in influenza A viruses and…

From Patent Search