Covid-19 Sentry

Contents

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

From Preprints

• Do People Use Games to Compensate for Psychological Needs During Crises? A Mixed-Methods Study of Gaming During COVID-19 Lockdowns -
  Do people use games to cope with adverse life events and crises? Research informed by self-determination theory proposes that people might compensate for thwarted basic psychological needs in daily life by seeking out games that satisfy those lacking needs. To test this, we conducted a preregistered mixed-method survey study (n = 285) on people’s gaming behaviours and need states during early stages of the COVID-19 pandemic (May 2020). We found qualitative evidence that gaming was an often actively sought out and successful means of replenishing particular needs, but one that could ‘backfire’ for some through an appraisal process discounting gaming as ‘unreal’. Meanwhile, contrary to our predictions, the quantitative data showed a “rich get richer, poor get poorer” pat- tern: need satisfaction in daily life positively correlated with need satisfaction in games. We derive methodological considerations and propose three potential explanations for this contradictory data pattern to pursue in future research.
  🖺 Full Text HTML: Do People Use Games to Compensate for Psychological Needs During Crises? A Mixed-Methods Study of Gaming During COVID-19 Lockdowns
• Validity Testing of the Conspiratorial Thinking and Anti-Expert Sentiment Scales during the COVID-19 Pandemic Across 24 Languages from a Large-Scale Global Dataset -
  In this study, we tested the validity across two scales addressing conspiratorial thinking that may influence behaviors related to public health and the COVID-19 pandemic. Using the COVIDiSTRESSII Global Survey data from 12,261 participants, we validated the 4-item Conspiratorial Thinking Scale and 3-item Anti-Expert Sentiment Scale across 24 languages and dialects that were used by at least 100 participants per language. We employed confirmatory factor analysis, measurement invariance test, and measurement alignment for internal consistency testing. To test convergent validity of the two scales, we assessed correlations with trust in seven agents related to government, science, and public health. Although scalar invariance was not achieved when measurement invariance test was conducted initially, we found that both scales can be employed in further international studies with measurement alignment. Moreover, both conspiratorial thinking and anti-expert sentiments were significantly and negatively correlated with trust in all agents. Findings from this study provide supporting evidence for the validity of both scales across 24 languages for future large-scale international research.
  🖺 Full Text HTML: Validity Testing of the Conspiratorial Thinking and Anti-Expert Sentiment Scales during the COVID-19 Pandemic Across 24 Languages from a Large-Scale Global Dataset
• Virtual Social Interaction and Loneliness Among Emerging Adults Amid the COVID-19 Pandemic -
  Many social activities moved online during the global COVID-19 pandemic, yet research investigating whether virtual social interactions facilitate social connectedness has been inconclusive. In this study, participants completed online questionnaires assessing objective social isolation, loneliness, mental health, and virtual social interactions. There was clear evidence for worsening mental health among emerging adults during the COVID-19 pandemic characterized by large increases in depressive symptoms (mean increase = 8.35, 95% CI [6.97, 9.73], t(118) = 118, p < .001), and large decrements in happiness (mean decrease = -0.71, 95% CI [-0.84, -0.57], t(118) = 10.09, p < .001) and social satisfaction (mean decrease = -0.81, 95% CI [-1.00,-0.62], t(115) = 8.28, p < .001) post-pandemic onset. In line with expectations, those living in larger households amid the pandemic reported lower levels of loneliness and higher levels of happiness. A negative association was found between household size (an index of objective social isolation) and loneliness, b = -3.01, t(79) = 2.60, p = .011, 95% CI [-5.32, -0.71], and a positive association was found between household size and happiness, b = 22.86, t(75) = 3.30, p = .001, 95% CI [9.06, 36.65]. However, contrary to expectations, there was no association between loneliness and frequency of virtual social interactions. There was also no association between frequency of virtual social interactions and either happiness or depression. More research investigating social connectedness in the context of virtual social interactions is warranted.
  🖺 Full Text HTML: Virtual Social Interaction and Loneliness Among Emerging Adults Amid the COVID-19 Pandemic
• Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs -

  Accurate stratification of patients with post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies. However, the natural history of long COVID is incompletely understood and characterized by an extremely wide range of manifestations that are difficult to analyze computationally. In addition, the generalizability of machine learning classification of COVID-19 clinical outcomes has rarely been tested. We present a method for computationally modeling PASC phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Our approach defines a nonlinear similarity function that maps from a feature space of phenotypic abnormalities to a matrix of pairwise patient similarity that can be clustered using unsupervised machine learning procedures. Using k-means clustering of this similarity matrix, we found six distinct clusters of PASC patients, each with distinct profiles of phenotypic abnormalities. There was a significant association of cluster membership with a range of pre-existing conditions and with measures of severity during acute COVID-19. Two of the clusters were associated with severe manifestations and displayed increased mortality. We assigned new patients from other healthcare centers to one of the six clusters on the basis of maximum semantic similarity to the original patients. We show that the identified clusters were generalizable across different hospital systems and that the increased mortality rate was consistently observed in two of the clusters. Semantic phenotypic clustering can provide a foundation for assigning patients to stratified subgroups for natural history or therapy studies on PASC.

  🖺 Full Text HTML: Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs
• Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative -

  Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p=5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.

  🖺 Full Text HTML: Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
• Antigenic evolution of SARS-CoV-2 in immunocompromised hosts -

  Prolonged infections of immunocompromised individuals have been proposed as a crucial source of new variants of SARS-CoV-2 during the COVID-19 pandemic. In principle, sustained within-host antigenic evolution in immunocompromised hosts could allow novel immune escape variants to emerge more rapidly, but little is known about how and when immunocompromised hosts play a critical role in pathogen evolution. Here, we use a simple mathematical model to understand the effects of immunocompromised hosts on the emergence of immune escape variants in the presence and absence of epistasis. We show that when the pathogen does not have to cross a fitness valley for immune escape to occur (no epistasis), immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level (epistasis), then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore facilitating rather than simply speeding up antigenic evolution. Our results suggest that better genomic surveillance of infected immunocompromised individuals and better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.

  🖺 Full Text HTML: Antigenic evolution of SARS-CoV-2 in immunocompromised hosts
• Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting -
  SARS-CoV-2 is currently causing an unprecedented pandemic. While vaccines are massively deployed, we still lack effective large-scale antiviral therapies. In the quest for antivirals targeting conserved structures, we focused on molecules able to bind viral RNA secondary structures. Aminoglycosides are a class of antibiotics known to interact with the ribosomal RNA of both prokaryotes and eukaryotes and have previously been shown to exert antiviral activities by interacting with viral RNA. Here we show that the aminoglycoside geneticin is endowed with antiviral activity against all tested variants of SARS-CoV-2, in different cell lines and in a respiratory tissue model at non-toxic concentrations. The mechanism of action is an early inhibition of RNA replication and protein expression mediated by direct interaction with the -1 programmed ribosomal frameshift (PRF) signal. Using in silico modeling, we have identified a potential binding site of geneticin in the pseudoknot of frameshift RNA motif. Moreover, we have selected, through virtual screening, additional RNA binding compounds, interacting with the same site with increased potency.
  🖺 Full Text HTML: Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting
• ROLE OF DEEP LEARNING STRATEGIES IN DETECTING COVID-19 PNEUMONIA -
  In this chapter, we will describe the various deep learning strategies used in detecting COVID-19 pneumonia with the help of different models.
  🖺 Full Text HTML: ROLE OF DEEP LEARNING STRATEGIES IN DETECTING COVID-19 PNEUMONIA
• Vaccination shapes evolutionary trajectories of SARS-CoV-2 -
  The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, as well as antigenic changes that reduce the cross-immunity induced by previous infections or vaccinations. How this functional variation shapes the global evolutionary dynamics has remained unclear. Here we show that selection induced by vaccination impacts on the recent antigenic evolution of SARS-CoV-2; other relevant forces include intrinsic selection and antigenic selection induced by previous infections. We obtain these results from a fitness model with intrinsic and antigenic fitness components. To infer model parameters, we combine time-resolved sequence data, epidemiological records, and cross-neutralisation assays. This model accurately captures the large-scale evolutionary dynamics of SARS-CoV-2 in multiple geographical regions. In particular, it quantifies how recent vaccinations and infections affect the speed of frequency shifts between viral variants.Our results show that timely neutralisation data can be harvested to identify hotspots of antigenic selection and to predict the impact of vaccination on viral evolution.
  🖺 Full Text HTML: Vaccination shapes evolutionary trajectories of SARS-CoV-2
• Who believes in conspiracy theories? A meta-analysis on personality correlates -
  Conspiracy theories are ubiquitous (e.g., 9/11, COVID-19) and can have negative consequences (e.g., prejudice). Thus, there is an increasing need for evidence-based recommendations (e.g. possible target groups) with respect to interventions and prevention measures. Present Bayesian three-level meta-analysis (686 correlations, 127 independent samples) includes a synthesis of the extant literature with respect to 12 personality correlates and their relationship with conspiracy beliefs. On average, people who believe in pseudoscience, suffer from paranoia or schizotypy, are narcissistic or religious/spiritual and have relatively low cognitive ability, are more likely to believe in conspiracy theories. Heterogeneity was partially explained by the examined moderators and no strong evidence for publication bias was found. Implications for developing tailored interventions are discussed in the article.
  🖺 Full Text HTML: Who believes in conspiracy theories? A meta-analysis on personality correlates
• Safety and biodistribution of NanoligomersTM targeting SARS-CoV-2 genome for treatment of COVID-19 -
  As the world braces to enter its third year in the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to treatment of COVID-19 as an endemic disease. Here, we present a novel compound, called SBCoV202, that specifically and tightly binds the translation initiation site of RNA-dependent RNA polymerase within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, inhibiting viral replication. SBCoV202 is a Nanoligomer,TM a molecule that includes peptide nucleic acid sequences capable of binding viral RNA with single-base-pair specificity to accurately target the viral genome. The compound has been shown to be safe and nontoxic in mice, with favorable biodistribution, and has shown efficacy against SARS-CoV-2 in vitro. Safety and biodistribution were assessed after three separate administration methods, namely intranasal, intravenous, and intraperitoneal. Safety studies showed the Nanoligomer caused no outward distress, immunogenicity, or organ tissue damage, measured through observation of behavior and body weight, serum levels of cytokines, and histopathology of fixed tissue, respectively. SBCoV202 was evenly biodistributed throughout the body, with most tissues measuring Nanoligomer concentrations well above the compound KD of 3.37 nM. In addition to favorable availability to organs such as the lungs, lymph nodes, liver, and spleen, the compound circulated through the blood and was rapidly cleared through the renal and urinary systems. The favorable biodistribution and lack of immunogenicity and toxicity set Nanoligomers apart from other antisense therapies, while the adaptability of the nucleic acid sequence of Nanoligomers provides a defense against future emergence of drug resistance, making these molecules an attractive potential treatment for COVID-19.
  🖺 Full Text HTML: Safety and biodistribution of NanoligomersTM targeting SARS-CoV-2 genome for treatment of COVID-19
• Regulation of mRNA transcripts, protein isoforms, glycosylation and spatial localization of ACE2 and other SARS-CoV-2-associated molecules in human airway epithelium upon viral infection and type 2 inflammation -
  SARS-CoV-2 infection continues to pose a significant life threat, especially in patients with comorbidities. It remains unknown, if asthma or allergen- and virus-induced airway inflammation are risk factors or can constitute some forms of protection against COVID-19. ACE2 and other SARS-CoV-2-related host proteins are limiting factors of an infection, expression of which is regulated in a more complex way than previously anticipated. Hence, we studied the expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in house dust mite (HDM)-, interleukin-13 (IL-13)- and human rhinovirus (RV)-induced inflammation in the primary human bronchial airway epithelium of healthy subjects and patients with asthma. IL-13 decreased the expression of long ACE2 mRNA and glycosylation of full-length ACE2 protein via alteration of the N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. RV infection increased short ACE2 mRNA, but it did not influence its protein expression. HDM exposure did not affect ACE2 mRNA or protein. IL-13 and RV significantly regulated mRNA, but not protein expression of TMPRSS2 and NRP1. Regulation of ACE2 and other host proteins was similar in healthy and asthmatic epithelium, underlining the lack of intrinsic differences, but rather the dependence on the inflammatory milieu in the airways.
  🖺 Full Text HTML: Regulation of mRNA transcripts, protein isoforms, glycosylation and spatial localization of ACE2 and other SARS-CoV-2-associated molecules in human airway epithelium upon viral infection and type 2 inflammation
• Evasion of neutralizing antibodies by Omicron sublineage BA.2.75 -
  Towards the end of 2021, SARS-CoV-2 vaccine effectiveness was threatened by the emergence of the Omicron clade (B.1.1.529), with more than 30 mutations in spike. Recently, several sublineages of Omicron, including BA.2.12.1, BA.4, and BA.5, have demonstrated even greater immune evasion, and are driving waves of infections across the globe. One emerging sublineage, BA.2.75, is increasing in frequency in India and has been detected in at least 15 countries as of 19 July 2022. Relative to BA.2, BA.2.75 carries nine additional mutations in spike. Here we report the sensitivity of the BA.2.75 spike to neutralization by a panel of clinically-relevant and pre-clinical monoclonal antibodies, as well as by serum from blood donated in Stockholm, Sweden, before and after the BA.1/BA.2 infection wave. BA.2.75 does not show greater immune evasion than the currently-dominating BA.5 in our set of serum samples, and exhibits moderate susceptibility to tixagevimab and cilgavimab that form a widely used monoclonal antibody cocktail (Evusheld).
  🖺 Full Text HTML: Evasion of neutralizing antibodies by Omicron sublineage BA.2.75
• A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex -
  We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease.
  🖺 Full Text HTML: A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex
• The First Geographic Identification by Country of Sustainable Mutations of SARS-COV-2 Sequence Samples: Worldwide Natural Selection Trends -
  The high mutation rates of RNA viruses, coupled with short generation times and large population sizes, allow viruses to evolve rapidly and adapt to the host environment. The rapidity of viral mutation also causes problems in developing successful vaccines and antiviral drugs. With the spread of SARS-CoV-2 worldwide, thousands of mutations have been identified, some of which have relatively high incidences, but their potential impacts on virus characteristics remain unknown. The present study analyzed mutation patterns, SARS-CoV-2 AASs retrieved from the GISAID database containing 10,500,000 samples. Python 3.8.0 programming language was utilized to pre-process FASTA data, align to the reference sequence, and analyze the sequences. Upon completion, all mutations discovered were categorized based on geographical regions and dates. The most stable mutations were found in nsp1(8% S135R), nsp12(99.3% P323L), nsp16 (1.2% R216C), envelope (30.6% T9I), spike (97.6% D614G), and Orf8 (3.5% S24L), and were identified in the United States on April 3, 2020, and England, Gibraltar, and, New Zealand, on January 1, 2020, respectively. The study of mutations is the key to improving understanding of the function of the SARS-CoV-2, and recent information on mutations helps provide strategic planning for the prevention and treatment of this disease. Viral mutation studies could improve the development of vaccines, antiviral drugs, and diagnostic assays designed with high accuracy, specifically useful during pandemics. This knowledge helps to be one step ahead of new emergence variants.
  🖺 Full Text HTML: The First Geographic Identification by Country of Sustainable Mutations of SARS-COV-2 Sequence Samples: Worldwide Natural Selection Trends

From Clinical Trials

• Puerto Rico COVID-19 Vaccine Uptake Study - Condition:   COVID-19
  Intervention:   Other: Educational intervention
  Sponsors:   University of Puerto Rico;   National Institutes of Health (NIH);   National Institute on Minority Health and Health Disparities (NIMHD)
  Recruiting

• Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity - Condition:   COVID-19
  Intervention:   Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors
  Sponsor:   Central Hospital, Nancy, France
  Not yet recruiting

• Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients - Condition:   Severe COVID-19
  Interventions:   Biological: Coronavirus-2-specific T cells;   Other: standard of care (SOC)
  Sponsors:   George Papanicolaou Hospital;   General Hospital Of Thessaloniki Ippokratio
  Recruiting

• Beta-glucans for Hospitalised Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: MC 3x3;   Drug: Placebo
  Sponsors:   Concentra Educacion e Investigación Biomédica;   Wohlstand Pharmaceutical
  Not yet recruiting

• A Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa - Condition:   COVID-19
  Intervention:   Drug: Molnupiravir 200 mg
  Sponsors:   University of Witwatersrand, South Africa;   Bill and Melinda Gates Foundation
  Not yet recruiting

• Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities - Condition:   COVID-19
  Interventions:   Behavioral: Full Intervention;   Other: Enhanced Usual Care
  Sponsors:   Kaiser Permanente;   Patient-Centered Outcomes Research Institute;   Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
  Recruiting

• Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough - Condition:   Post COVID-19
  Intervention:   Drug: Montelukast Sodium Tablets
  Sponsor:   Assiut University
  Completed

• Topical Antibacterial Agents for Prevention of COVID-19 - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Drug: Neosporin;   Other: Vaseline
  Sponsors:   Yale University;   Bill and Melinda Gates Foundation
  Not yet recruiting

• **NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - Condition:   COVID-19 Pandemic
  Interventions:   Drug: Placebo;   Drug: Experimental drug
  Sponsor:   Medesis Pharma SA
  Recruiting

• Safety and Immunogenicity of Recombinant COVID-19 Vaccine (Sf9 Cell) as a Booster - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: Recombinant COVID-19 Vaccine (Sf9 Cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsor:   WestVac Biopharma Co., Ltd.
  Recruiting

• Safety and Immunogenicity of Recombinant COVID-19 Variant Vaccine (Sf9 Cell) as a Booster - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: Recombinant COVID-19 variant Vaccine (Sf9 Cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: mRNA COVID-19 vaccine (Moderna);   Biological: Viral Vector COVID-19 vaccine (AstraZeneca)
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection - Conditions:   COVID-19;   Rehabilitation
  Interventions:   Other: Respiratory training with the use of resistance set on respiratory muscle trainer;   Other: Respiratory training without resistance set on respiratory muscle trainer
  Sponsor:   Medical University of Bialystok
  Recruiting

• Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention - Condition:   Post-acute COVID-19 Syndrome
  Intervention:   Behavioral: PACS Coping and Recovery (PACS-CR) Intervention
  Sponsor:   VA Office of Research and Development
  Not yet recruiting

• Mineralocorticoid Use in COVID-19 Patients - Conditions:   COVID-19;   ARDS
  Intervention:   Drug: Fludrocortisone Acetate 0.1 MG
  Sponsor:   Ain Shams University
  Completed

• Xanthohumol as an Adjuvant Therapy in Critically Ill COVID-19 Patients - Condition:   COVID-19 Respiratory Infection
  Intervention:   Biological: Xanthohumol - prenylated chalcone extracted from female inflorescences of hop cones (Humulus lupus). Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/
  Sponsor:   Medical University of Lublin
  Suspended

From PubMed

• Self-Masked Aldehyde Inhibitors of Human Cathepsin L Are Potent Anti-CoV-2 Agents - Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of compounds, self-masked…

• In Vitro Evaluation and Mitigation of Niclosamide’s Liabilities as a COVID-19 Treatment - Niclosamide, an FDA-approved oral anthelmintic drug, has broad biological activity including anticancer, antibacterial, and antiviral properties. Niclosamide has also been identified as a potent inhibitor of SARS-CoV-2 infection in vitro , generating interest in its use for the treatment or prevention of COVID-19. Unfortunately, there are several potential issues with using niclosamide for COVID-19, including low bioavailability, significant polypharmacology, high cellular toxicity, and unknown…

• Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2 - Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor….

• Exploration of molecular targets and mechanisms of Chinese medicinal formula Acacia Catechu -Scutellariae Radix in the treatment of COVID-19 by a systems pharmacology strategy - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In China, the Acacia catechu (AC)-Scutellariae Radix (SR) formula has been widely used for pulmonary infection in clinical practice for several centuries. However, the potential role and mechanisms of this formula against COVID-19 remains unclear. The present study was designed to dissect the active ingredients, molecular targets, and the therapeutic mechanisms of AC-SR formula in the…

• The global succinylation of SARS-CoV-2-infected host cells reveals drug targets - SARS-CoV-2, the causative agent of the COVID-19 pandemic, undergoes continuous evolution, highlighting an urgent need for development of novel antiviral therapies. Here we show a quantitative mass spectrometry-based succinylproteomics analysis of SARS-CoV-2 infection in Caco-2 cells, revealing dramatic reshape of succinylation on host and viral proteins. SARS-CoV-2 infection promotes succinylation of several key enzymes in the TCA, leading to inhibition of cellular metabolic pathways. We…

• Ubiquitination of SARS-CoV-2 NSP6 and ORF7a Facilitates NF-κB Activation - Patients with severe coronavirus disease 2019 tend to have high levels of proinflammatory cytokines, which eventually lead to cytokine storm and the development of acute respiratory distress syndrome. However, the detailed molecular mechanisms of proinflammatory cytokine production remain unknown. Here, we screened severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes and found that nonstructural protein 6 (NSP6) and open reading frame 7a (ORF7a) activated the NF-κB pathway. NSP6…

• Recent Progress in the Development of Opaganib for the Treatment of Covid-19 - The Covid-19 pandemic driven by the SARS-CoV-2 virus continues to exert extensive humanitarian and economic stress across the world. Although antivirals active against mild disease have been identified recently, new drugs to treat moderate and severe Covid-19 patients are needed. Sphingolipids regulate key pathologic processes, including viral proliferation and pathologic host inflammation. Opaganib (aka ABC294640) is a first-in-class clinical drug targeting sphingolipid metabolism for the…

• A computational evaluation of FDA medicines’ ability to inhibit hypoxia-inducible factor prolyl hydroxylase-2 (PHD-2) for acute respiratory distress syndrome - COVID-19 infection is associated with a significant fatality rate in individuals suffering from severe acute respiratory distress syndrome (ARDS). Among the several possibilities, inhibition of hypoxia-inducible factor prolyl hydroxylase-2 or prolyl hydroxylase domain-containing protein 2 (PHD2) in a hypoxia-independent way is a prospective therapeutic target for the treatment of ARDS. Vadadustat, Roxadustat, Daprodustat, Desidustat, and Enarudustat are the available clinical trial inhibitors….

• Targeting the Conserved Sequence of the Substrate for the Proteinase of Severe-Acute-Respiratory-Syndrome-Coronavirus-2 (SARS-CoV-2) Using Nano-Networks: Efficacy, Stability, and No Cytotoxicity - Herein, we designed a nano peptide that contains three important motifs for targeting the chemotrypsin-like cysteine protease (3CL^(pro)) which is the enzyme responsible for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) replication. The novel nano peptide contains the Nap Phe-Phe motif that is responsible for peptide self-assembly, an octapeptide (Ser-Ala-Val-Leu-Gln-Ser-Gly-Phe) motif where the enzyme recognizes the substrate and induces enzyme sensitivity, and a tetrapeptide…

• Inhibiting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants: Targeting the Spike and Envelope Proteins Using Nanomaterial Like Peptides - Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant death, economic crisis, and the world to almost completely shut down. This present study focused on targeting the novel SARS-CoV-2 envelope protein, which has not been frequently mutating, and the S protein with a much larger peptide capable of inhibiting virus-mammalian cell attraction. In doing so, molecular dynamics software was used here to model six peptides…

• Complement C3 activation in the ICU: Disease and therapy as Bonnie and Clyde - Patients in the intensive care unit (ICU) often straddle the divide between life and death. Understanding the complex underlying pathomechanisms relevant to such situations may help intensivists select broadly acting treatment options that can improve the outcome for these patients. As one of the most important defense mechanisms of the innate immune system, the complement system plays a crucial role in a diverse spectrum of diseases that can necessitate ICU admission. Among others, myocardial…

• Application of emetine in SARS-CoV-2 treatment: regulation of p38 MAPK signaling pathway for preventing emetine-induced cardiac complications - Emetine is one of the most highly potent anti-SARS-CoV-2 agents ever identified. In addition to having strong anti-SARS-CoV-2 activities, emetine has other valuable therapeutic effects such as strong anti-inflammatory and anti-arterial pulmonary hypertension (APH) properties, which are suitable for the treatment of COVID-19. Its proper concomitant therapeutic effect has led researchers to test this compound in clinical trials to combat COVID-19. However, due to the risks of cardiac…

• The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint - The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to…

• Molnupiravir for the treatment of COVID-19 - Molnupiravir (MK-4482, EIDD-2801) is a promising broad-spectrum experimental antiviral developed by Merck & Co. It is a nucleoside analogue prodrug that undergoes rapid conversion into nucleoside triphosphate (NTP) by intracellular metabolic processes. NTP inhibits viral polymerase by acting as an alternative substrate. Molnupiravir was initially developed to treat influenza and Venezuelan equine encephalitis virus (VEEV) infection as it exerts its antiviral activity by inhibiting RNA-dependent…

• COVID-19 vaccine hesitancy in Africa: a scoping review - CONCLUSIONS: Our review demonstrated the contextualized and multifaceted reasons inhibiting or encouraging vaccine uptake in African countries. This evidence is key to operationalizing interventions based on facts as opposed to assumptions. Our paper provided important considerations for addressing the challenge of COVID-19 vaccine hesitancy and blunting the impact of the pandemic in Africa.

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