Covid-19 Sentry

Contents

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

From Preprints

• Getting culturally appropriate health messages out in a hurry: Developing a communications campaign for COVID-19 testing in a Vietnamese-American community. -
  Background. Developing health communication materials can be time-consuming. During infectious disease outbreaks, health communication materials to limit the spread of the disease are needed promptly, which hampers the ability to get input from the target audience. This paper proposes a strategy to rapidly develop culturally appropriate communication materials with adequate community feedback. Context. Our strategy is illustrated using a communication campaign to encourage COVID-19 testing in a Vietnamese-American enclave in New Orleans. The community has a high vulnerability to COVID-19 infection due to their isolation from mainstream public health information and COVID-19 related stigma and discrimination. Programmatic elements. The project included community-based COVID-19 testing services and communication activities to increase awareness of the testing centers and encourage frequent testing. Our proposed strategy involves two main components: 1) use of a research team with existing trust relationship with the target community and that includes researchers from that community, and 2) use of a cultural broker and community-based gatekeepers. Free PCR tests were offered daily at a community-based health center. Another community-based organization promoted testing and issued referrals. We developed brochures and posters to increase awareness of the testing services. The cultural broker and community-based partners helped identify key message concepts that were salient for the target audience, as well as the objectives and content of the materials, which were then reviewed by the entire team. The entire team provided feedback on mock-ups of the materials and subsequent revisions. Finalized materials were placed at both partner organizations and at strategic locations throughout the community and supplemented with newspaper advertisements and community outreach. Discussion. During infectious disease outbreaks there is a need to rapidly develop new health communication materials. Our proposed strategy strikes a balance between the need to disseminate new materials with minimal delay and the need for community input by using a research team with an established trust relationship with the community, cultural brokers, and community-based gatekeepers. Effective planning for public health emergencies must start long before the crisis occurs. Collaborations between researchers and community leaders should be developed and nurtured, and community representatives should be involved throughout the entire project.
  🖺 Full Text HTML: Getting culturally appropriate health messages out in a hurry: Developing a communications campaign for COVID-19 testing in a Vietnamese-American community.
• Challenges faced by Madagascar’s protected area network during COVID-19 were very real -
  We appreciate Andrianambinina at al. engaging with our paper “Elevated fires during COVID-19 lockdown and the vulnerability of protected areas” published in Nature Sustainability in May 2022. In their response, Andrianambinina et al. question the extent to which protected area management in Madagascar was interrupted by the COVID-19 pandemic and our interpretation that the patterns we observe in excess fires are a result of this. They also question our use of the World Database on Protected Areas (WDPA) as the source of shape files for Madagascar’s protected areas. We respond to these points in turn.
  🖺 Full Text HTML: Challenges faced by Madagascar’s protected area network during COVID-19 were very real
• Neutralizing antibody responses and cellular responses against severe acute respiratory syndrome coronavirus 2 omicron subvariant BA.5 after an mRNA severe acute respiratory syndrome coronavirus 2 vaccine dose in kidney transplant recipients -
  We examined the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein IgG antibody and neutralizing antibody titers and cellular immunity in 73 uninfected recipients and 17 uninfected healthy controls who received three doses of a coronavirus 2019 mRNA vaccine. Neutralizing antibody titers were evaluated using GFP-carrying recombinant SARS-CoV-2 with spike protein of B.1.1, omicron BA.1, or BA.5. For cellular immunity, peripheral blood mononuclear cells were stimulated with peptides corresponding to spike protein antigens of B.1.1, BA.1, and BA.5; spike-specific CD4/CD8 memory T cells were evaluated using intracellular cytokine staining. The median IgG antibody titers were 7.8 AU/mL in recipients and 143.0 AU/mL in healthy controls (p < 0.0001). Neutralizing antibody titers against all three viral variants were significantly lower in recipients (p < 0.0001). The number of spike-specific CD8 + memory T cells significantly decreased in recipients (p < 0.0001). Twenty recipients and seven healthy controls additionally received a bivalent omicron-containing booster vaccine, and IgG antibody and neutralizing antibody titers increased in both groups; however, the increase was significantly lower in recipients. Recipients did not gain sufficient immunity with a third dose of vaccine, suggesting a need to explore methods other than vaccines.
  🖺 Full Text HTML: Neutralizing antibody responses and cellular responses against severe acute respiratory syndrome coronavirus 2 omicron subvariant BA.5 after an mRNA severe acute respiratory syndrome coronavirus 2 vaccine dose in kidney transplant recipients
• Genetic architecture and shared mechanisms of common ′neglected′ diseases -

  The authors have withdrawn this manuscript owing to the paper being rewritten with a stronger focus on COVID-19 upon request from UK Biobank and to comply more clearly with the primary care data usage agreement. An updated version will be re-uploaded as soon as possible. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding authors.

  🖺 Full Text HTML: Genetic architecture and shared mechanisms of common ′neglected′ diseases
• Health inequalities in SARS-CoV-2 infection during the second wave in England: REACT-1 study -

  Abstract Background The rapid spread of SARS-CoV-2 infection caused high levels of hospitalisation and deaths in late 2020 and early 2021 during the second wave in England. Severe disease during this period was associated with marked health inequalities across ethnic and sociodemographic subgroups. Methods We analysed risk factors for test-positivity for SARS-CoV-2, based on self-administered throat and nose swabs in the community during rounds 5 to 10 of the REal-time Assessment of Community Transmission-1 (REACT-1) study between 18 September 2020 and 30 March 2021. Results Compared to white ethnicity, people of Asian and black ethnicity had a higher risk of infection during rounds 5 to 10, with odds of 1.46 (1.27, 1.69) and 1.35 (1.11, 1.64) respectively. Among ethnic subgroups, the highest and the second-highest odds were found in Bangladeshi and Pakistan participants at 3.29 (2.23, 4.86) and 2.15 (1.73, 2.68) respectively when compared to British whites. People in larger (compared to smaller) households had higher odds of infection. Health care workers with direct patient contact and care home workers showed higher odds of infection compared to other essential/key workers. Additionally, the odds of infection among participants in public-facing activities or settings were greater than among those not working in those activities or settings. Interpretation Planning for future severe waves of respiratory pathogens should include policies to reduce inequality in risk of infection by ethnicity, household size, and occupational activity.

  🖺 Full Text HTML: Health inequalities in SARS-CoV-2 infection during the second wave in England: REACT-1 study
• Questions of ethics during the Covid-19 pandemic emerging from problems of data fraud and health risks -
  In more than two years of the global health crisis of the Covid-19 pandemic, ethical issues regarding health data have been emerging quickly to the central focus of the global scientific community. Many papers have been retracted because of data problems, including those from prestigious journals. For example, two papers in The Lancet and the New England Journal of Medicine (NEJM) were retracted due to concerns regarding the veracity of datasets. Elisabeth Bik, an academic image sleuth, has found that 4% of more than 20000 biomedical papers she checked contained problematic image duplications; her efforts have led to at least 172 retractions. When the lives and well-being of countless people are at stake, and all eyes are on science, such mistakes could be (and have been) disruptive toward public trust, which might further fuel conspiracy theories, science-denying, and anti-vax attitudes. We require health data of good ethical standards, but who will be responsible if such standards are not met?
  🖺 Full Text HTML: Questions of ethics during the Covid-19 pandemic emerging from problems of data fraud and health risks
• What a world-class research paper taught us -
  Our research lab back then published a review paper in HSSComms on January 18, 2022. That paper presented the principles and systemic thinking endorsing the foundational concepts of this collaborative platform. Only two months after our publication, a group of scientists from Sweden published another paper evaluating scientific advice regarding the COVID-19 pandemic, an extremely hot topic and highly debatable throughout the pandemic. The Swedish paper has taught us something invaluable, which we would like to share here with the community.
  🖺 Full Text HTML: What a world-class research paper taught us
• Call for papers: Science lessons from the COVID-19 pandemic -
  The SM3D Portal invites colleagues to provide their perspectives, assessments, and analyses on science’s involvement in coping with the epidemic to the “Science lessons from the COVID-19 pandemic” collection. The collection is intended to supplement academic efforts to generate insightful lessons from the COVID-19 catastrophe and to create measures to safeguard our communities from future pandemics.
  🖺 Full Text HTML: Call for papers: Science lessons from the COVID-19 pandemic
• COVID-19 made some population groups more miserable than others -
  The COVID-19 pandemic has brought a lot of suffering to many people across the whole world. The disease not only directly devastated people’s health but also disrupted normal lifestyles and increased the risk of mental health issues [1,2]. A recent study by Kim et al. (2022) published in the Journal of Personalized Medicine (IF 3.508, according to JCR 2022) [3] revealed that the prevalence of stress, depression, and suicidal attempts did not change significantly during the COVID-19 pandemic compared to before. However, the 19- to 39-year-old group in the 2020 group had a higher rate of depression. The study employed data from the Korea National Health and Nutrition Examination Survey in 2019 and 2020, with a sample of >=19-year-old 11,873 participants. The research sample is highly representative of the Korean population.
  🖺 Full Text HTML: COVID-19 made some population groups more miserable than others
• Tetherin restricts SARS-CoV-2 replication despite antagonistic effects of Spike and ORF7a -
  SARS-CoV-2 infection induces interferon-stimulated genes, one of which encodes Tetherin, a transmembrane protein inhibiting the release of various enveloped viruses from infected cells. Previous studies revealed that SARS-CoV encodes two Tetherin antagonists: the Spike protein (S) inducing lysosomal degradation of Tetherin, and ORF7a altering its glycosylation. SARS-CoV-2 ORF7a has also been shown to antagonize Tetherin. Therefore, we here investigated whether SARS-CoV-2 S is also a Tetherin antagonist and compared the abilities and mechanisms of S and ORF7a in counteracting Tetherin. SARS-CoV and SARS-CoV-2 S reduced Tetherin cell surface levels in a cell type-dependent manner, possibly related to the basal protein levels of Tetherin. In HEK293T cells, under conditions of high exogenous Tetherin expression, SARS-CoV-2 S and ORF7a reduced total Tetherin levels much more efficiently than the respective counterparts derived from SARS-CoV. Nevertheless, ORF7a from both strains was able to alter Tetherin glycosylation. The ability to decrease total protein levels of Tetherin was conserved among S proteins from different SARS-CoV-2 variants (D614G, Cluster 5, , {gamma}, {delta}, o). While SARS-CoV-2 S and ORF7a both colocalized with Tetherin, only ORF7a directly interacted with the restriction factor. Despite the presence of two Tetherin antagonists, however, SARS-CoV-2 replication in Caco-2 cells was further enhanced upon Tetherin knockout. Altogether, our data show that endogenous Tetherin restricts SARS-CoV-2 replication, and that the antiviral activity of Tetherin is partially counteracted by two viral antagonists with differential and complementary modes of action, S and ORF7a.
  🖺 Full Text HTML: Tetherin restricts SARS-CoV-2 replication despite antagonistic effects of Spike and ORF7a
• The Human Microglia Atlas (HuMicA) Unravels Changes in Homeostatic and Disease-Associated Microglia Subsets across Neurodegenerative Conditions -
  Dysregulated microglia activation, leading to neuroinflammation, is currently considered to be of major relevance in the development and progression of neurodegenerative diseases. The initial M1/M2 dual activation classification for microglia is now considered outdated. Even the "disease-associated microglia" (DAM) phenotype, firstly described in mice, has proven insufficient to precisely represent the multitude of microglia phenotypes in pathology. In this study, we have constructed a transcriptomic atlas of human brain immune cells by integrating single-nucleus (sn)RNA-seq datasets from multiple neurodegenerative conditions. Sixteen datasets were included, comprising 295 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) dataset included 60,557 nuclei and revealed 11 microglial subpopulations distributed across all pathological and healthy conditions. Among these, we identified four different homeostatic clusters as well as pathological phenotypes. These included two stages of early and late activation of the DAM phenotype and the disease-inflammatory macrophage (DIM) phenotype, which was recently described in mice, and is also present in human microglia, as indicated by our analysis. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution to the establishment of pathological phenotypes. Our analysis showed overall depletion of four substates of homeostatic microglia, and expansion of niche subpopulations within the DAM and DIM spectrum across distinct neurodegenerative pathologies. The HuMicA is an invaluable resource tool used to support further advances in the study of microglia biology through healthy and disease settings.
  🖺 Full Text HTML: The Human Microglia Atlas (HuMicA) Unravels Changes in Homeostatic and Disease-Associated Microglia Subsets across Neurodegenerative Conditions
• Frequency of Atypical Pulmonary Manifestations of COVID-19 Patients on Chest CTscan: A cross-sectional study -

  Background: Chest CT examination is significant in COVID-19 diagnosis due to its high sensitivity. Although typical chest CT findings have been discussed thoroughly in the literature throughout the pandemic, we aimed to investigate the prevalence of the atypical conclusions during the start of the Omicron variant insurgency and compare the results to studies conducted before its outbreak. Methods: 606 confirmed COVID-19 cases were included in this study based on inclusion and exclusion criteria during January and February 2022. Demographic information of patients, including age and sex, was recorded. The computed tomography (CT) examination was carried out using a 100-slice scanner (Philips Brilliance 6 CT Scanner). One radiology attending and one resident evaluated SARSCoV- 2 RT-PCR-positive patients for atypical pulmonary CT findings. The obtained data were evaluated using R software version 4.1.1. Results: 55% of patients were female, and the median age was 56 (IQR: 42, 69 59% of patients had atypical findings on their pulmonary CT examination. These findings showed that pleural abnormalities were the most frequent atypicalfindings, with pleural thickening being the most common (17%). The double halo sign represented the least frequent atypical sign (0.2%). Conclusion: Atypical findings were more prevalent in this study than its predecessors, while we acknowledge that other factors, such as study design and patient population, could have impacted it. The presence of atypical signs generally was not correlated with specific demographic groups, while some of these signs were more frequent in some groups.

  🖺 Full Text HTML: Frequency of Atypical Pulmonary Manifestations of COVID-19 Patients on Chest CTscan: A cross-sectional study
• Lower Urinary Tract Symptoms in a prospective cohort of COVID-19 survivors -

  Purpose: To analyze the prevalence of lower urinary tract symptoms (LUTS) in patients who survived moderate and severe forms of COVID-19 and the risk factors for LUTS six months after hospital discharge. Materials and Methods: In this prospective cohort study, patients were evaluated six months after being hospitalized due to COVID-19. LUTS were assessed using the International Prostate Symptom Score. General health was assessed through the Hospital Anxiety and Depression Scale and the EQ5D-L5 scale, which evaluates mobility, ability to perform daily activities, pain and discomfort and completed a self-perception health evaluation. Results: Of 255 participants, 54.1% were men and the median age was 57.3 [44.3 / 66.6] years. Pre-existing comorbidities included diabetes (35.7%), hypertension (54.5%), obesity (30.2%) and physical inactivity (65.5%). 124 (48.6%) had a hospital stay >15 days, 181 (71.0%) were admitted to an ICU and 124 (48.6%) needed mechanical ventilation. Median IPSS score was 6 [3-11] and did not differ between men and women. Moderate to severe LUTS affected 108 (42.4%) patients (40.6% men and 44.4% women; p=0.610). Nocturia (58.4%) and frequency (45.9%) were the most prevalent symptoms and urgency was the only symptom that affected men (29.0%) and women (44.4%) differently (p=0.013). LUTS significantly impacted the quality of life of 60 (23.5%) patients with women more severely affected (p=0.004). Preexisting diabetes, hypertension and self-perception of worse general health were associated with LUTS. Conclusions: LUTS are highly prevalent and bothersome six months after hospitalization due to COVID-19. Assessment of LUTS may help ensure appropriate diagnosis and treatment in these patients.

  🖺 Full Text HTML: Lower Urinary Tract Symptoms in a prospective cohort of COVID-19 survivors
• Graphical Learning and Causal Inference for Drug Repurposing -

  Abstract Gene expression profiles that connect drug perturbations, disease gene expression signatures, and clinical data are important for discovering potential drug repurposing indications. However, the current approach to gene expression reversal has several limitations. First, most methods focus on validating the reversal expression of individual genes. Second, there is a lack of causal approaches for identifying drug repurposing candidates. Third, few methods for passing and summarizing information on a graph have been used for drug repurposing analysis, with classical network propagation and gene set enrichment analysis being the most common. Fourth, there is a lack of graph-valued association analysis, with current approaches using real-valued association analysis one gene at a time to reverse abnormal gene expressions to normal gene expressions. To overcome these limitations, we propose a novel causal inference and graph neural network (GNN)-based framework for identifying drug repurposing candidates. We formulated a causal network as a continuous constrained optimization problem and developed a new algorithm for reconstructing large-scale causal networks of up to 1,000 nodes. We conducted large-scale simulations that demonstrated good false positive and false negative rates. To aggregate and summarize information on both nodes and structure from the spatial domain of the causal network, we used directed acyclic graph neural networks (DAGNN). We also developed a new method for graph regression in which both dependent and independent variables are graphs. We used graph regression to measure the degree to which drugs reverse altered gene expressions of disease to normal levels and to select potential drug repurposing candidates. To illustrate the application of our proposed methods for drug repurposing, we applied them to phase I and II L1000 connectivity map perturbational profiles from the Broad Institute LINCS, which consist of gene-expression profiles for thousands of perturbagens at a variety of time points, doses, and cell lines, as well as disease gene expression data under-expressed and over-expressed in response to SARS-CoV-2.

  🖺 Full Text HTML: Graphical Learning and Causal Inference for Drug Repurposing
• Loss of severe respiratory syncytial virus infection-associated antibody function during the peak of the COVID-19 pandemic mitigation measures -

  Studies have linked reduced respiratory syncytial virus-specific Fc-mediated phagocytic function and complement deposition to more severe infection. This study shows a loss of these functions during the first year of COVID-19 pandemic. These findings corroborate other data supporting a general waning of RSV antibody functions in absence of viral circulation.

  🖺 Full Text HTML: Loss of severe respiratory syncytial virus infection-associated antibody function during the peak of the COVID-19 pandemic mitigation measures

From Clinical Trials

• Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients - Condition:   COVID-19
  Intervention:   Dietary Supplement: Freeze-dried Mare Milk (Saumal)
  Sponsor:   Asfendiyarov Kazakh National Medical University
  Not yet recruiting

• Effects of Exercise Training on Patients With Long COVID-19 - Condition:   Long COVID-19
  Intervention:   Behavioral: Exercise training
  Sponsor:   Guangdong Provincial People’s Hospital
  Recruiting

• A Phase 2/3 Open-Label Study to Evaluate the Safety and Immunogenicity of an XBB.1.5 (Omicron Subvariant) SARS CoV-2 rS Vaccine. - Condition:   COVID-19
  Interventions:   Biological: XBB.1.5 Vaccine (Booster);   Biological: XBB.1.5 Vaccine (single dose)
  Sponsor:   Novavax
  Not yet recruiting

• A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults - Condition:   COVID-19
  Interventions:   Biological: mRNA-CR-04 vaccine 10μg;   Biological: mRNA-CR-04 vaccine 30μg;   Biological: mRNA-CR-04 vaccine 100μg;   Drug: Placebo
  Sponsor:   GlaxoSmithKline
  Not yet recruiting

• A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine;   Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)
  Sponsor:   Novavax
  Not yet recruiting

• Non-ventilated Prone Positioning in the COVID-19 Population - Conditions:   COVID-19;   Proning;   Oxygenation;   Length of Stay
  Interventions:   Other: Proning group;   Other: Control group
  Sponsor:   Baylor St. Luke’s Medical Center
  Completed

• HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19 - Conditions:   COVID-19;   Delirium;   Critical Illness
  Interventions:   Combination Product: Active HD-tDCS;   Combination Product: Sham HD-tDCS
  Sponsors:   Suellen Andrade;   City University of New York
  Completed

• RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms - Conditions:   Long COVID-19;   Long COVID
  Interventions:   Drug: Paxlovid 25 day dosing;   Drug: Paxlovid 15 day dosing;   Drug: Control
  Sponsor:   Kanecia Obie Zimmerman
  Not yet recruiting

• A Study on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults - Condition:   SARS-CoV-2
  Interventions:   Biological: CV0701 Bivalent High dose;   Biological: CV0701 Bivalent Medium dose;   Biological: CV0701 Bivalent Low dose;   Biological: CV0601 Monovalent High dose;   Biological: Control vaccine
  Sponsors:   GlaxoSmithKline;   CureVac
  Not yet recruiting

• RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms - Conditions:   Long COVID;   Long Covid19;   Long Covid-19
  Interventions:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham
  Sponsor:   Duke University
  Not yet recruiting

• Directed Topical Drug Delivery for Treatment for PASC Hyposmia - Condition:   Post Acute Sequelae Covid-19 Hyposmia
  Interventions:   Drug: Beclomethasone;   Other: Placebo;   Device: Microsponge
  Sponsor:   Duke University
  Not yet recruiting

• RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms - Conditions:   Long COVID;   Long Covid19;   Long Covid-19
  Interventions:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham
  Sponsor:   Duke University
  Not yet recruiting

• Impact of COVID-19 on Sinus Augmentation Surgery - Condition:   Bone Loss
  Interventions:   Procedure: Sinus lift in patients with positive COVID-19 history;   Procedure: Sinus lift with negative COVID-19 history
  Sponsor:   Cairo University
  Completed

• Telerehabilitation for Post COVID-19 Condition - Conditions:   Long COVID;   Chronic Fatigue Syndrome
  Intervention:   Other: Telerehabilitation program based on cardiorespiratory principles
  Sponsors:   Université de Sherbrooke;   Hotel Dieu Hospital
  Completed

• Immunogenicity and Safety of Concomitant Administration of Bivalent COVID-19 Vaccines With Influenza Vaccines - Conditions:   Immune Response;   Safety
  Interventions:   Biological: bivalent BNT162b2 mRNA original/omicron BA.4-5 vaccine;   Biological: quadrivalent influenza vaccine
  Sponsors:   Catholic Kwandong University;   Korea University Guro Hospital
  Active, not recruiting

From PubMed

• Novel computational and drug design strategies for inhibition of monkeypox virus and Babesia microti: molecular docking, molecular dynamic simulation and drug design approach by natural compounds - CONCLUSION: These advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further in vitro and in vivo…

• Reflections on access to care for heavy menstrual bleeding: Past, present, and in times of the COVID-19 pandemic - The symptom of heavy menstrual bleeding (HMB) affects at least a quarter of reproductive-age menstruators. However, given the variance in diagnosing the underlying causes, barriers, and inequity in access to care for HMB, and therefore reporting of HMB, this figure is likely to be a gross underestimate. HMB can have a detrimental impact on quality of life. From the limited reports available it is estimated that around 50%-80% of people with HMB do not seek care for this debilitating symptom, and…

• Inhibition by components of Glycyrrhiza uralensis of 3CLpro and HCoV-OC43 proliferation - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). 3CLpro is a key enzyme in coronavirus proliferation and a treatment target for COVID-19. In vitro and in silico, compounds 1-3 from Glycyrrhiza uralensis had inhibitory activity and binding affinity for 3CLpro. These compounds decreased HCoV-OC43 cytotoxicity in RD cells. Moreover, they inhibited viral growth by reducing the amounts of the necessary proteins (M, N,…

• An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen - The threat to global health caused by three highly pathogenic human coronaviruses (HCoV), SARS-CoV-2, MERS-CoV and SARS-CoV, calls for the development of pan-HCoV therapeutics and vaccines. This study reports the design and engineering of a recombinant protein designated HR1LS. It contains 3 linked molecules, each consisting of three structural domains, including a heptad repeat 1 (HR1), a central helix (CH), and a stem helix (SH) region, in the S2 subunit of SARS-CoV-2 spike (S) protein. It was…

• Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation - NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2’O-methyl-transferase (2’O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM…

• Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease - Recently, geraniin has been identified as a potent antiviral agent targeting SARS-CoV-2 main protease (Mpro). Considering the potential of geraniin in COVID-19 treatment, a stringent validation for its Mpro inhibition is necessary. Herein, we rigorously evaluated the in vitro inhibitory effect of geraniin on Mpro using the fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data indicate that…

• Crystal structures of main protease (M^pro) mutants of SARS-CoV-2 variants bound to PF-07304814 - There is an urgent need to develop effective antiviral drugs to prevent the viral infection caused by constantly circulating SARS-CoV-2 as well as its variants. The main protease (M^(pro)) of SARS-CoV-2 is a salient enzyme that plays a vital role in viral replication and serves as a fascinating therapeutic target. PF-07304814 is a covalent inhibitor targeting SARS-CoV-2 M^(pro) with favorable inhibition potency and drug-like properties, thus making it a promising drug candidate for the treatment…

• Direct blue 53, a biological dye, inhibits SARS-CoV-2 infection by blocking ACE2 and spike interaction in vitro and in vivo - COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of pivotal importance to slow down the epidemic swiftly. In this study, we identified five azo compounds as effective antiviral drugs to SARS-CoV-2, and mechanism study revealed their targets for impeding viral particles’ ability to bind to host receptors. Direct Blue 53, which displayed the strongest inhibitory impact, inhibited five…

• Chicoric Acid Presented NLRP3-Mediated Pyroptosis through Mitochondrial Damage by PDPK1 Ubiquitination in an Acute Lung Injury Model - Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells were…

• Therapeutic effects of tea polyphenol-loaded nanoparticles coated with platelet membranes on LPS-induced lung injury - Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles…

• Combination of Chinese herbal medicine and conventional western medicine for coronavirus disease 2019: a systematic review and meta-analysis - CONCLUSIONS: Potentially, CHM listed in this study, as an adjunctive therapy, combining with CWM is an effective and safe therapy mode for COVID-19. However, more high-quality RCTs are needed to draw more accurate conclusions.

• SARS-CoV-2 main protease targeting potent fluorescent inhibitors: Repurposing thioxanthones - The coronavirus disease, COVID-19, is the major focus of the whole world due to insufficient treatment options. It has spread all around the world and is responsible for the death of numerous human beings. The future consequences for the disease survivors are still unknown. Hence, all contributions to understand the disease and effectively inhibit the effects of the disease have great importance. In this study, different thioxanthone based molecules, which are known to be fluorescent compounds,…

• Identification of a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection - We previously identified GAPDH as one of the cyclic adenosine diphosphoribose (cADPR)’s binding proteins and found that GAPDH participates in cADPR-mediated Ca^(2+) release from ER via ryanodine receptors (RyRs). Here we aimed to chemically synthesize and pharmacologically characterize novel cADPR analogues. Based on the simulated cADPR-GAPDH complex structure, we performed the structure-based drug screening, identified several small chemicals with high docking scores to cADPR’s binding pocket…

• Discovery and evaluation of active compounds from Xuanfei Baidu formula against COVID-19 via SARS-CoV-2 M^pro - CONCLUSION: Acteoside is regarded as a representative active natural compound in XFBD to inhibit replication of SARS-CoV-2, which provides the antiviral evidence and some insights into the identification of SARS-CoV-2 M^(pro) natural inhibitors.

• Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2 - CONCLUSION: Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.

From Patent Search