Covid-19 Sentry

Contents

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

From Preprints

• Mixed Attention with Deep Supervision for Delineation of COVID Infection in Lung CT -

  The COVID-19 pandemic, with its multiple variants, has placed immense pressure on the global healthcare system. An early effective screening and grading become imperative towards optimizing the limited available resources of the medical facilities. Computed tomography (CT) provides a significant non-invasive screening mechanism for COVID-19 infection. An automated segmentation of the infected volumes in lung CT is expected to significantly aid in the diagnosis and care of patients. However, an accurate demarcation of lesions remains problematic due to their irregular structure and location(s) within the lung. A novel deep learning architecture, Mixed Attention Deeply Supervised Network (MiADS-Net), is proposed for delineating the infected regions of the lung from CT images. Incorporating dilated convolutions with varying dilation rates, into a mixed attention framework, allows capture of multi-scale features towards improved segmentation of lesions having different sizes and textures. Mixed attention helps prioritise relevant feature maps to be probed, along with those regions containing crucial information within these maps. Deep supervision facilitates discovery of robust and discriminatory characteristics in the hidden layers at shallower levels, while overcoming the vanishing gradient. This is followed by estimating the severity of the disease, based on the ratio of the area of infected region in each lung with respect to its entire volume. Experimental results, on three publicly available datasets, indicate that the MiADS-Net outperforms several state-of-the-art architectures in the COVID-19 lesion segmentation task; particularly in defining structures involving complex geometries.

  🖺 Full Text HTML: Mixed Attention with Deep Supervision for Delineation of COVID Infection in Lung CT
• Suicide deaths during the COVID-19 pandemic in the United States, by region, March 1, 2020-June 30, 2022 -

  Introduction: There were concerns that suicide deaths might increase due to Covid-19 pandemic-related stressors. Previous research demonstrated that suicide deaths actually decreased in 2020 in the US. An update covering 2021-2022 with regional data is warranted. Methods: Observational cohort, US and regional data. Expected monthly deaths were modeled using pre-pandemic US and regional data (2015-2020). Mortality data was accessed from CDC public reporting. Results: We find that suicide deaths in the United States were below expected levels throughout the pandemic period (March 1, 2020-June 30,2022) with >4,100 fewer suicide deaths than would have been expected to occur during the study period. Stratifying suicide mortality by US Census Bureau region yielded statistically significant decreases from expected suicide deaths in all regions except the Midwest, (which recorded no significant change in suicide deaths during the overall pandemic period). Conclusion: Suicide mortality is down in the US since the pandemic began, through June 30, 2022. Possible explanations include an early 9coming together9 effect; Later, increased access to mental health resources and a greater focus on mental health in the media may have reduced stigma and barriers in seeking necessary psychiatric care.

  🖺 Full Text HTML: Suicide deaths during the COVID-19 pandemic in the United States, by region, March 1, 2020-June 30, 2022
• Development of a Novel Medium Throughput Flow-Cytometry Based Micro-Neutralisation Test for SARS-CoV-2 with Applications in Clinical Vaccine Trials and Antibody Screening -

  Quantifying neutralising capacity of circulating SARS-COV-2 antibodies is critical in evaluating protective humoral immune responses generated post-infection/post-vaccination. Here we describe a novel medium-throughput flow cytometry-based micro-neutralisation test to evaluate Neutralising Antibody (NAb) responses against live SARS-CoV-2 Wild Type and Variants of Concern (VOC) in convalescent/vaccinated populations. Flow Cytometry-Based Micro-Neutralisation Test (Micro-NT) was performed in 96-well plates using clinical isolates WT-B, WT-B.177.18 and/or VOCs Beta and Omicron. Plasma samples (All Ireland Infectious Diseases (AIID) Cohort) were serially diluted (8 points, half-log) from 1/20 and pre-incubated with SARS-CoV-2 (1h, 37°C). Virus-plasma mixture were added onto VERO E6/VERO E6 TMPRSS2 cells for 18h. Percentage infected cells was analysed by automated flow cytometry following trypsinisation, fixation and SARS-CoV-2 Nucleoprotein intracellular staining. Half-maximal Neutralisation Titres (NT50) were determined using four-parameter logistic regression. Our assay was compared to Plaque Reduction Neutralisation Test (PRNT) and validated against WHO anti-SARS-CoV-2 Immunoglobulin Standards. Using WHO Standards with low, medium or high anti-SARS-CoV-2 IgG, both Micro-NT and PRNT achieved comparable NT50 values. Micro-NT was found to be highly reproducible (inter-assay CV of 11.64%). Screening 190 convalescent samples and 11 COVID-19 naive controls (AIID cohort) we demonstrated that Micro-NT has broad dynamic range differentiating NT50s <1/20 to >1/5000. We could also characterise immune-escape VOC observing up to 10-fold reduction in NT50 against SARS-CoV-2 Beta variant. Our flow cytometry-based Micro-NT is a robust and reliable assay to quantify NAb titres, and has been selected as an endpoint in clinical trials. It has higher throughput (96 well format versus 12 well) and reduced infection time (18h vs 48-96h) compared to the gold standard PRNT.

  🖺 Full Text HTML: Development of a Novel Medium Throughput Flow-Cytometry Based Micro-Neutralisation Test for SARS-CoV-2 with Applications in Clinical Vaccine Trials and Antibody Screening
• A deep generative model of the SARS-CoV-2 spike protein predicts future variants -
  SARS-CoV-2 has demonstrated a robust ability to adapt in response to environmental pressures—increasing viral transmission and evading immune surveillance by mutating its molecular machinery. While viral sequencing has allowed for the early detection of emerging variants, methods to predict mutations before they occur remain limited. This work presents SpikeGPT2, a deep generative model based on ProtGPT2 and fine-tuned on SARS-CoV-2 spike (S) protein sequences deposited in the NIH Data Hub before May 2021. SpikeGPT2 achieved 88.8% next-residue prediction accuracy and successfully predicted amino acid substitutions found only in a held-out set of spike sequences deposited on or after May 2021, to which SpikeGPT2 was never exposed. When compared to several other methods, SpikeGPT2 achieved the best performance in predicting such future mutations. SpikeGPT2 also predicted several novel variants not present in the NIH SARS-CoV-2 Data Hub. A binding affinity analysis of all 54 generated substitutions identified 5 (N439A, N440G, K458T, L492I, and N501Y) as predicted to simultaneously increase S/ACE2 affinity, and decrease S/tixagevimab+cilgavimab affinity. Of these, N501Y has already been well-described to increase transmissibility of SARS-CoV-2. These findings indicate that SpikeGPT2 and other similar models may be employed to identify high-risk future variants before viral spread has occurred.
  🖺 Full Text HTML: A deep generative model of the SARS-CoV-2 spike protein predicts future variants
• Discovery of highly potent small molecule pan-coronavirus fusion inhibitors -
  The unprecedented pandemic of COVID-19, caused by a novel coronavirus, SARS-CoV-2, has led to massive human suffering, death, and economic devastation worldwide. The virus is mutating fast to more transmissible and infectious variants. The Delta variant (B.1.617.2), initially identified in India, and the omicron variant (BA.4 and BA.5) have spread worldwide. In addition, recently alarming antibody evasive SARS-CoV-2 subvariants, BQ and XBB, have been reported. These new variants may pose a substantial challenge to controlling the spread of this virus. Therefore, the continued development of novel drugs having pan-coronavirus inhibition to treat and prevent infection of COVID-19 is urgently needed. These drugs will be critically important in dealing with new pandemics that will emerge in the future. We report the discovery of several highly potent small molecule pan-coronavirus inhibitors. One of which, NBCoV63, showed low nM potency against SARS-CoV-2 (IC50: 55 nM), SARS-CoV (IC50: 59 nM), and MERS-CoV (IC50: 75 nM) in pseudovirus-based assays with excellent selectivity indices (SI: as high as > 900) demonstrating its pan-coronavirus inhibition. NBCoV63 showed equally effective antiviral potency against SARS-CoV-2 mutant (D614G) and several variants of concerns (VOCs) such as B.1.617.2 (Delta), B.1.1.529/BA.1 and BA.4/BA.5 (Omicron) and K417T/E484K/N501Y (Gamma). NBCoV63 also showed similar efficacy profiles to Remdesivir against authentic SARS-CoV-2 (Hong Kong strain) and two of its variants (Delta and Omicron) by plaque reduction in Calu3 cells. Additionally, we show that NBCoV63 inhibits virus-mediated cell-to-cell fusion in a dose-dependent manner. Furthermore, the Absorption, distribution, metabolism, and excretion (ADME) data of NBCoV63 demonstrated drug-like properties.
  🖺 Full Text HTML: Discovery of highly potent small molecule pan-coronavirus fusion inhibitors
• Cell division tracing combined with single-cell transcriptomics reveals new cell types and differentiation paths in the regenerating mouse lung -
  Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of new therapeutic approaches for lung diseases. We combined new mouse models that allow diphtheria toxin (DTA)-mediated depletion of specific epithelial cell types and GFP-labeling of dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncovered new cell types, some of which likely represent epithelial precursors, propose goblet cells as progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also found that DTA-expressing cells can persist in the lung, express specific inflammatory factors, and resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to defined epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions.
  🖺 Full Text HTML: Cell division tracing combined with single-cell transcriptomics reveals new cell types and differentiation paths in the regenerating mouse lung
• A Systematic Survey of Reversibly Covalent Dipeptidyl Inhibitors of the SARS-CoV-2 Main Protease -
  SARS-CoV-2 is the coronavirus pathogen of the currently prevailing COVID-19 pandemic. It relies on its main protease (MPro) for replication and pathogenesis. MPro is a demonstrated target for the development of antivirals for SARS-CoV-2. Past studies have systematically explored tripeptidyl inhibitors such as nirmatrelvir as MPro inhibitors. However, dipeptidyl inhibitors especially those with a spiro residue at their P2 position have not been systematically investigated. In this work, we synthesized about 30 reversibly covalent dipeptidyl MPro inhibitors and characterized them on in vitro enzymatic inhibition potency, structures of their complexes with MPro, cellular MPro inhibition potency, antiviral potency, cytotoxicity, and in vitro metabolic stability. Our results indicated that MPro has a flexible S2 pocket that accommodates dipeptidyl inhibitors with a large P2 residue and revealed that dipeptidyl inhibitors with a large P2 spiro residue such as (S)-2-azaspiro[4,4]nonane-3-carboxylate and (S)-2-azaspiro[4,5]decane-3-carboxylate have optimal characteristics. One compound MPI60 containing a P2 (S)-2-azaspiro[4,4]nonane-3-carboxylate displayed high antiviral potency, low cellular cytotoxicity, and high in vitro metabolic stability and can be potentially advanced to further preclinical tests.
  🖺 Full Text HTML: A Systematic Survey of Reversibly Covalent Dipeptidyl Inhibitors of the SARS-CoV-2 Main Protease
• Higher Angiotensin I Converting Enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease. -
  The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of death in the elderly. Cognitive decline due to Alzheimer’s disease (AD) is frequent in the geriatric population disproportionately affected by the COVID-19 pandemic. Interestingly, central nervous system (CNS) manifestations have been reported in SARS-CoV-2-infected patients. In this study, we investigated the levels of Angiotensin I Converting Enzyme 2 (ACE2), the main entry receptor of SARS-COV-2 in cells, in postmortem parietal cortex samples from two independent AD cohorts, totalling 142 persons. Higher concentrations of ACE2 protein and mRNA were found in individuals with a neuropathological diagnosis of AD compared to age-matched healthy control subjects. Brain levels of soluble ACE2 were inversely associated with cognitive scores (p = 0.02), markers of pericytes (PDGFR{beta}, p=0.02 and ANPEP, p = 0.007) and caveolin1 (p = 0.03), but positively correlated with soluble amyloid-{beta} peptides (A{beta}) concentrations (p = 0.01) and insoluble phospho-tau (S396/404, p = 0.002). No significant differences in ACE2 were observed in the 3xTgAD mouse model of tau and A{beta} neuropathology. Results from immunofluorescence and Western blots showed that ACE2 protein is mainly localized in neurons in the human brain but predominantly in microvessels in the mouse brain. The present data show that an AD diagnosis is associated with higher levels of soluble ACE2 in the human brain, which might contribute to a higher risk of CNS SARS-CoV-2 infection.
  🖺 Full Text HTML: Higher Angiotensin I Converting Enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease.
• Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology. -
  Aging is the primary risk factor for most neurodegenerative diseases, and recently coronavirus disease 2019 (COVID-19) has been associated with severe neurological manifestations that can eventually impact neurodegenerative conditions in the long-term. The progressive accumulation of senescent cells in vivo strongly contributes to brain aging and neurodegenerative co-morbidities but the impact of virus-induced senescence in the aetiology of neuropathologies is unknown. Here, we show that senescent cells accumulate in physiologically aged brain organoids of human origin and that senolytic treatment reduces inflammation and cellular senescence; for which we found that combined treatment with the senolytic drugs dasatinib and quercetin rejuvenates transcriptomic human brain aging clocks. We further interrogated brain frontal cortex regions in postmortem patients who succumbed to severe COVID-19 and observed increased accumulation of senescent cells as compared to age-matched control brains from non-COVID-affected individuals. Moreover, we show that exposure of human brain organoids to SARS-CoV-2 evoked cellular senescence, and that spatial transcriptomic sequencing of virus-induced senescent cells identified a unique SARS-CoV-2 variant-specific inflammatory signature that is different from endogenous naturally-emerging senescent cells. Importantly, following SARS-CoV-2 infection of human brain organoids, treatment with senolytics blocked viral retention and prevented the emergence of senescent corticothalamic and GABAergic neurons. Furthermore, we demonstrate in human ACE2 overexpressing mice that senolytic treatment ameliorates COVID-19 brain pathology following infection with SARS-CoV-2. In vivo treatment with senolytics improved SARS-CoV-2 clinical phenotype and survival, alleviated brain senescence and reactive astrogliosis, promoted survival of dopaminergic neurons, and reduced viral and senescence-associated secretory phenotype gene expression in the brain. Collectively, our findings demonstrate SARS-CoV-2 can trigger cellular senescence in the brain, and that senolytic therapy mitigates senescence-driven brain aging and multiple neuropathological sequelae caused by neurotropic viruses, including SARS-CoV-2.
  🖺 Full Text HTML: Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology.
• Benchmarking of analytical combinations for COVID-19 outcome prediction using single-cell RNA sequencing data -
  The advances of single-cell transcriptomic technologies have led to increasing use of single-cell RNA sequencing (scRNA-seq) data in large-scale patient cohort studies. The resulting high-dimensional data can be summarised and incorporated into patient outcome prediction models in several ways, however, there is a pressing need to understand the impact of analytical decisions on such model quality. In this study, we evaluate the impact of analytical choices on model choices, ensemble learning strategies and integration approaches on patient outcome prediction using five scRNA-seq COVID-19 datasets. First, we examine the difference in performance between using each single-view feature space versus multi-view feature space. Next, we survey multiple learning platforms from classical machine learning to modern deep learning methods. Lastly, we compare different integration approaches when combining datasets is necessary. Through benchmarking such analytical combinations, our study highlights the power of ensemble learning, consistency among different learning methods and robustness to dataset normalisation when using multiple datasets as the model input.
  🖺 Full Text HTML: Benchmarking of analytical combinations for COVID-19 outcome prediction using single-cell RNA sequencing data
• The Benefits of Living with Close Others: A Longitudinal Examination of Mental Health Before and During a Global Stressor -
  For better or worse, the people we live with may exert a powerful influence on our mental health, perhaps especially during times of stress. The COVID-19 pandemic—a large-scale stressor that prompted health recommendations to stay home to reduce disease spread—provided a unique context for examining how the people we share our homes with may shape our mental health. A seven-wave longitudinal study assessed mental health month-to-month before and during the pandemic (February through September, 2020) in two diverse samples of U.S. adults (N = 656; N = 544). Pre-registered analyses demonstrated that people living with close others (children and/or romantic partners) experienced better well-being before and during the pandemic’s first six months. These groups also experienced unique increases in ill-being during the pandemic’s onset, but parents’ ill-being also recovered more quickly. These findings highlight the crucial protective function of close relationships for mental health both generally and amidst a pandemic.
  🖺 Full Text HTML: The Benefits of Living with Close Others: A Longitudinal Examination of Mental Health Before and During a Global Stressor
• Debriefing works: Successful retraction of misinformation following a fake news study -
  In recent years there has been an explosion of research on misinformation, often involving experiments where participants are presented with fake news stories and subsequently debriefed. In order to avoid potential harm to participants or society, to is imperative that we establish whether debriefing procedures remove any lasting influence of misinformation. In the current study, we followed-up 1547 participants one week after they had been exposed to fake news stories about COVID-19 and then provided with a detailed debriefing. We found that false memories and beliefs for previously-seen fake stories declined sharply from the original study, suggesting that the debrief was effective. Moreover, the debriefing also resulted in reduced false memories and beliefs for novel fake stories, suggesting a broader impact on participants’ willingness to accept misinformation. Effects of misinformation on planned health behaviours observed in the original study were also eliminated at follow-up. Our findings suggest that when a careful and thorough debriefing procedure is followed, researchers can safely and ethically conduct misinformation research on sensitive topics.
  🖺 Full Text HTML: Debriefing works: Successful retraction of misinformation following a fake news study
• Effecting behaviour change using an artificial intelligence chatbot: A pilot randomised controlled study -
  Chatbots have the potential to effect large-scale behaviour change because they are accessible through social media, flexible, scalable, and automatically gather data. Yet research on the feasibility and effectiveness of chatbot-administered behaviour change interventions is sparse. There is no guarantee that established behaviour change interventions are effective when implemented in chatbots given the unique human-machine interaction dynamics. In this pilot study, we test whether an advanced, natural language processing-based chatbot can effect behaviour change using animations embedded in conversations with users. Specifically, we evaluated whether the chatbot could increase understanding and intentions to adopt protective behaviours during the pandemic in a real world cohort. We randomised 59 participants from culturally and linguistically diverse populations to three groups, receiving either a compassion intervention, an exponential growth intervention or no intervention. We measured participants’ attitudes about leaving the house for different reasons and their intentions to get tested if they experienced symptoms. We found that the chatbot reduced uncertainty about appropriate COVID-19 protective behaviours and that the exponential growth bias intervention increased participants’ likelihood of getting tested. This study provides preliminary evidence that chatbots augmented with animations can spark behaviour change, with potential for applications in diverse and underrepresented groups, highlighting the need for further research on this topic.
  🖺 Full Text HTML: Effecting behaviour change using an artificial intelligence chatbot: A pilot randomised controlled study
• When is a “small effect” actually large and impactful? -
  Reporting of effect sizes is standard practice in psychology and psychiatry research. However, interpretation of these effect sizes can be meaningless or misleading – in particular, the evaluation of specific effect sizes as “small”, “medium” and “large” can be inaccurate depending on the research context. A real-world example of this is research into the mental health of children and young people during the Covid-19 pandemic. Evidence suggests that clinicians and services are struggling with increased demand, yet population studies looking at the difference in mental health before and during the pandemic report effect sizes that are deemed “small”. In this short review we utilise simulations to demonstrate that a relatively small shift in mean scores on mental health measures can indicate a large shift in the number of cases of anxiety and depression when scaled up to an entire population. This shows that “small” effect sizes can in some contexts be large and impactful.
  🖺 Full Text HTML: When is a “small effect” actually large and impactful?
• Post-pandemic modeling of COVID-19: Waning immunity determines recurrence frequency -

  There are many factors in the current phase of the COVID-19 pandemic that signal the need for new modeling ideas. In fact, most traditional infectious disease models do not address adequately the waning immunity, in particular as new emerging variants have been able to brake the immune shield acquired either by previous infection by a different strain of the virus, or by inoculation of vaccines not effective for the current variant. Furthermore, in a post-pandemic landscape in which reporting is no longer a default, it is impossible to have reliable quantitative data at the population level. Our contribution to COVID-19 post-pandemic modeling is a simple mathematical predictive model along the age-distributed population framework, that can take into account the waning immunity in a transparent and easily controllable manner. Numerical simulations show that under static conditions, the model produces periodic solutions that are qualitatively similar to the reported data, with the period determined by the immunity waning profile. Evidence from the mathematical model indicates that the immunity dynamics is the main factor in the recurrence of infection spikes, however, irregular perturbation of the transmission rate, due to either mutations of the pathogen or human behavior, may result in suppression of recurrent spikes, and irregular time intervals between consecutive peaks. The spike amplitudes are sensitive to the transmission rate and vaccination strategies, but also to the skewness of the profile describing the waning immunity, suggesting that these factors should be taken into consideration when making predictions about future outbreaks.

  🖺 Full Text HTML: Post-pandemic modeling of COVID-19: Waning immunity determines recurrence frequency

From Clinical Trials

• Digital Tools to Expand COVID-19 Testing in Exposed Individuals in Cameroon - Condition:   COVID-19
  Intervention:   Other: Digital based contact tracing
  Sponsors:   Elizabeth Glaser Pediatric AIDS Foundation;   Find
  Recruiting

• Evaluation of the Outcome of COVID-19 Patients Discharged Home on Oxygen Therapy - Condition:   COVID-19
  Intervention:   Other: Phone satisfaction questionnaire
  Sponsor:   Centre Hospitalier René Dubos
  Not yet recruiting

• Postural Changes and Severe COVID-19 - Condition:   COVID-19
  Intervention:   Behavioral: Postural interventions based on pulmonary imaging
  Sponsor:   Wuhan Union Hospital, China
  Recruiting

• Efficacy and Safety of Jaktinib in Patients With COVID-19 Pneumonia. - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Jaktinib;   Drug: Placebo
  Sponsor:   First Affiliated Hospital of Zhejiang University
  Not yet recruiting

• A Chatbot to Enhance COVID-19 Knowledge - Condition:   COVID-19
  Interventions:   Device: chatbot;   Other: Printed educational booklet
  Sponsor:   Sun Yat-sen University
  Not yet recruiting

• Awaken Prone Positioning Ventinlation in COVID-19 Patients - Condition:   COVID-19
  Intervention:   Procedure: Awaken prone positioning ventilation
  Sponsor:   Southeast University, China
  Enrolling by invitation

• Effect of a Traditional Chinese Medicine Formulation on COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: Traditional Chinese Medicine Formulation;   Other: Placebo Treatment
  Sponsor:   First Affiliated Hospital Xi’an Jiaotong University
  Not yet recruiting

• Study of SHEN26 Capsule in Patients With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SHEN26 dose 1;   Drug: SHEN26 dose 2;   Drug: SHEN26 placebo
  Sponsor:   Shenzhen Kexing Pharmaceutical Co., Ltd.
  Recruiting

• Study on the Safety and Efficacy of Meplazumab for Injection Patients COVID-19 - Condition:   COVID-19
  Interventions:   Biological: Meplazumab foe injection;   Other: Normal saline
  Sponsor:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
  Not yet recruiting

• Study on the Safety and Efficacy of Meplazumab for Injection in Severe Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Biological: Meplazumab for injection;   Other: Normal saline
  Sponsor:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
  Not yet recruiting

• Bright Light Therapy for Post-COVID-19 Fatigue - Condition:   Post COVID-19 Condition
  Interventions:   Device: Bright light therapy;   Device: Dim red light therapy
  Sponsor:   Chinese University of Hong Kong
  Not yet recruiting

• Oropharyngeal Immunoprophylaxis With High Polyphenolic Olive Oil as Clinical Spectrum Mitigating Factor in COVID-19. - Condition:   COVID-19
  Intervention:   Dietary Supplement: High polyphenolic olive oil. (Early harvest olive oil).
  Sponsor:   Hospital General Nuestra Señora del Prado
  Completed

• A Randomized, Phase I Study of DNA Vaccine OC-007 as a Booster Dose of COVID-19 Vaccine - Conditions:   COVID-19 Respiratory Infection;   COVID-19 Vaccine Adverse Reaction
  Interventions:   Biological: DNA vaccine OC-007;   Other: Placebo
  Sponsor:   Matti Sällberg
  Not yet recruiting

• Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19 - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: FB2001;   Drug: FB2001 placebo
  Sponsor:   Frontier Biotechnologies Inc.
  Recruiting

• UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients - Conditions:   Mesenchymal Stem Cell;   COVID-19 Pneumonia
  Interventions:   Biological: umbilical cord mesenchymal stem cells;   Drug: paxlovid
  Sponsor:   Shanghai East Hospital
  Recruiting

From PubMed

• Antiviral Potential of Melissa officinalis L.: A Literature Review - The use of synthetic drugs has increased in recent years; however, herbal medicine is yet more trusted among a huge population worldwide; This could be due to minimal side effects, affordable prices, and traditional beliefs. Lemongrass (Melissa officinalis) has been widely used for reducing stress and anxiety, increasing appetite and sleep, reducing pain, healing wounds, and treating poisonous insect bites and bee stings for a long time. Today, research has shown that this plant can also fight…

• Broad-Spectrum Cyclopropane-Based Inhibitors of Coronavirus 3C-like Proteases: Biochemical, Structural, and Virological Studies - The advent of SARS-CoV-2, the causative agent of COVID-19, and its worldwide impact on global health, have provided the impetus for the development of effective countermeasures that can be deployed against the virus, including vaccines, monoclonal antibodies, and direct-acting antivirals (DAAs). Despite these efforts, the current paucity of DAAs has created an urgent need for the creation of an enhanced and diversified portfolio of broadly acting agents with different mechanisms of action that…

• Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19 - This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolising enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is…

• PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection - CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).

• Identification of Natural Products Inhibiting SARS-CoV-2 by Targeting Viral Proteases: A Combined in Silico and in Vitro Approach - In this study, an integrated in silico-in vitro approach was employed to discover natural products (NPs) active against SARS-CoV-2. The two SARS-CoV-2 viral proteases, i.e., main protease (M^(pro)) and papain-like protease (PL^(pro)), were selected as targets for the in silico study. Virtual hits were obtained by docking more than 140,000 NPs and NP derivatives available in-house and from commercial sources, and 38 virtual hits were experimentally validated in vitro using two enzyme-based…

• Potential of plant extracts in targeting SARS-CoV-2 main protease: an in vitro and in silico study - The deaths caused by the covid-19 pandemic have recently decreased due to a worldwide effort in vaccination campaigns. However, even vaccinated people can develop a severe form of the disease that requires ICU admission. As a result, the search for antiviral drugs to treat these severe cases has become a necessity. In this context, natural products are an interesting alternative to synthetic medicines used in drug repositioning, as they have been consumed for a long time through traditional…

• Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants - As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C(60) fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit…

• Detailed Insights into the Inhibitory Mechanism of New Ebselen Derivatives against Main Protease (M^pro) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) - SARS-CoV-2 main protease (M^(pro)/3CL(pro)) is a crucial target for therapeutics, which is responsible for viral polyprotein cleavage and plays a vital role in virus replication and survival. Recent studies suggest that 2-phenylbenzisoselenazol-3(2H)-one (ebselen) is a potent covalent inhibitor of M^(pro), which affects its enzymatic activity and virus survival. Herein, we synthesized various ebselen derivatives to understand the mechanism of M^(pro) inhibition by ebselen. Using ebselen…

• SARS-CoV-2 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses - SARS-CoV-2 infection can trigger strong inflammatory responses and cause severe lung damage in COVID-19 patients with critical illness. However, the molecular mechanisms by which the infection induces excessive inflammatory responses are not fully understood. Here, we report that SARS-CoV-2 infection results in the formation of viral Z-RNA in the cytoplasm of infected cells and thereby activates the ZBP1-RIPK3 pathway. Pharmacological inhibition of RIPK3 by GSK872 or genetic deletion of MLKL…

• D614G SARS-CoV-2 Pseudovirus Infectivity and Binding of Spike Protein to the ACE2 Receptor Inversely Correlates with Serum SARS-CoV-2-Specific IgG Levels - Understanding the functional characteristics of antibodies produced against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will assist in the determination of disease outcomes for this virus. In this study, the ability of antibodies to inhibit viral entry into the host cell through the interaction of the receptor binding domain of the viral spike protein and the angiotensin-converting enzyme 2 receptor on the human cell surface was investigated. The SARS-CoV-2 IgG levels in 20…

• Discovery of Natural Bisbenzylisoquinoline Analogs from the Library of Thai Traditional Plants as SARS-CoV-2 3CL^Pro Inhibitors: In Silico Molecular Docking, Molecular Dynamics, and In Vitro Enzymatic Activity - The emergence of SARS-CoV-2 in December 2019 has become a global issue due to the continuous upsurge in patients and the lack of drug efficacy for treatment. SARS-CoV-2 3CL^(Pro) is one of the most intriguing biomolecular targets among scientists worldwide for developing antiviral drugs due to its relevance in viral replication and transcription. Herein, we utilized computer-assisted drug screening to investigate 326 natural products from Thai traditional plants using structure-based virtual…

• Discovery of All-d-Peptide Inhibitors of SARS-CoV-2 3C-like Protease - During the replication process of SARS-CoV-2, the main protease of the virus [3-chymotrypsin-like protease (3CL^(pro))] plays a pivotal role and is essential for the life cycle of the pathogen. Numerous studies have been conducted so far, which have confirmed 3CL^(pro) as an attractive drug target to combat COVID-19. We describe a novel and efficient next-generation sequencing (NGS) supported phage display selection strategy for the identification of a set of SARS-CoV-2 3CL^(pro) targeting…

• High Throughput Screening for Drugs that Inhibit 3C-Like Protease in SARS-CoV-2 - The SARS coronavirus 2 (SARS-CoV-2) pandemic remains a major problem in many parts of the world and infection rates remain at extremely high levels. This high prevalence drives the continued emergence of new variants, and possibly ones that are more vaccine-resistant and that can drive infections even in highly vaccinated populations. The high rate of variant evolution makes clear the need for new therapeutics that can be clinically applied to minimize or eliminate the effects of COVID-19. With…

• Relationship between behavioral inhibition/activation system and Internet addiction among Chinese college students: The mediating effects of intolerance of uncertainty and self-control and gender differences - CONCLUSIONS: These findings extend our understanding of how BIS/BAS influence Internet addiction among college students and suggest that not only should training approaches based on intolerance of uncertainty and self-control be fully considered, but different intervention programs should be focused on gender sensitivity to maximize the intervention effect.

• miR-615 facilitates porcine epidemic diarrhea virus replication by targeting IRAK1 to inhibit type III interferon expression - Porcine epidemic diarrhea virus (PEDV) in the Coronavirus family is a highly contagious enteric pathogen in the swine industry, which has evolved mechanisms to evade host innate immune responses. The PEDV-mediated inhibition of interferons (IFNs) has been linked to the nuclear factor-kappa B (NF-κB) pathway. MicroRNAs (miRNAs) are involved in virus-host interactions and IFN-I regulation. However, the mechanism by which the PEDV regulates IFN during PEDV infection has not yet been investigated in…

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