Covid-19 Sentry

Contents

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

From Preprints

• Apropos of Universal Epitope Discovery for COVID-19 Vaccines: A Framework for Targeted Phage Display-Based Delivery and Integration of New Evaluation Tools -
  Targeted bacteriophage (phage) particles are potentially attractive yet inexpensive platforms for immunization. Herein, we describe targeted phage capsid display of an immunogenically relevant epitope of the SARS-CoV-2 Spike protein that is empirically conserved, likely due to the high mutational cost among all variants identified to date. This observation may herald an approach to developing vaccine candidates for broad-spectrum, towards universal, protection against multiple emergent variants of coronavirus that cause COVID-19.
  🖺 Full Text HTML: Apropos of Universal Epitope Discovery for COVID-19 Vaccines: A Framework for Targeted Phage Display-Based Delivery and Integration of New Evaluation Tools
• Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge -
  Early events in the host response to SARS-CoV-2 are thought to play a major role in determining disease severity. During pulmonary infection, the virus encounters both myeloid and epithelioid lineage cells that can either support or restrict pathogen replication as well as respond with host protective versus detrimental mediators. In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guerin (BCG) has been reported to confer non-specific resistance to unrelated pulmonary pathogens, a phenomenon attributed to the induction of long-lasting alterations within the myeloid cell compartment. Here we demonstrate that prior intravenous, but not subcutaneous, administration of BCG protects human-ACE2 transgenic mice against lethal challenge with SARS-CoV-2 and results in reduced viral loads in non-transgenic animals infected with an alpha variant. The observed increase in host resistance was associated with reductions in SARS-CoV-2-induced tissue pathology, inflammatory cell recruitment and cytokine production that multivariate analysis revealed to be only partially related to diminished viral load. We propose that this protection stems from BCG-induced alterations in the composition and function of the pulmonary cellular compartment that impact the innate response to the virus and the ensuing immunopathology.
  🖺 Full Text HTML: Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge
• (Machine) Learning the mutation signatures of SARS-CoV-2: a primer for predictive prognosis -
  Motivation: Continuous emergence of new variants through appearance, accumulation and disappearance of mutations in viruses is a hallmark of many viral diseases. SARS-CoV-2 and its variants have particularly exerted tremendous pressure on global healthcare system owing to their life threatening and debilitating implications. The sheer plurality of the variants and huge scale of genome sequence data available for Covid19 have added to the challenges of traceability of mutations of concern. The latter however provides an opportunity to utilize SARS-CoV-2 genomes and the mutations therein as “big data records” to comprehensively classify the variants through the (machine) learning of mutation patterns. The unprecedented sequencing effort and tracing of dis-ease outcomes provide an excellent ground for identifying important mutations by developing ma-chine learnt models or severity classifiers using mutation profile of SARS-CoV-2. This is expected to provide a significant impetus to the efforts towards not only identifying the mutations of concern but also exploring the potential of mutation driven predictive prognosis of SARS-CoV-2. Results: We describe how a graduated approach of building various severity specific machine learning classifiers, using only the mutation corpus of SARS- CoV-2 genomes, can potentially lead to the identification of important mutations and guide potential prognosis of infection. We demonstrate the applicability of model derived important mutations and use of Shapley values in order to identify the significant mutations of concern as well as for developing sparse models of outcome classification. A total of 77,284 outcome traced SARS-CoV-2 genomes were employed in this study which represented a total corpus of 30346 unique nucleotide mutations and 18647 amino acid mutations. Machine learning models pertaining to graduated classifiers of target outcomes namely “Asymptomatic, Mild, Symptomatic/Moderate, Severe and Fatal” were built considering the TRIPOD guidelines for predictive prognosis. Shapley values for model linked important mutations were employed to select significant mutations leading to identification of less than 20 outcome driving mutations from each classifier. We additionally describe the significance of adopting a “temporal modeling approach” to benchmark the predictive prognosis linked with continuously evolving pathogens. A chronologically distinct sampling is important in evaluating the performance of models trained on “past data” in accurately classifying prognosis linked with genomes of future (observed with new mutations). We conclude that while machine learning approach can play a vital role in identifying relevant mutations, caution should be exercised in using the mutation signatures for predictive prognosis in cases where new mutations have accumulated along with the previously observed mutations of concern.
  🖺 Full Text HTML: (Machine) Learning the mutation signatures of SARS-CoV-2: a primer for predictive prognosis
• Strikingly different roles of SARS-CoV-2 fusion peptides uncovered by neutron scattering -
  Coronavirus disease-2019 (COVID-19), a lethal respiratory illness caused by the coronavirus SARS-CoV-2, emerged in the end of 2019 and has since spread aggressively across the globe. A thorough understanding of the molecular mechanisms of cellular infection by coronaviruses is therefore of utmost importance. A critical stage in infection is the fusion between viral and host membranes. Here, we present a detailed investigation of the role of the SARS-CoV-2 Spike protein, and the influence of calcium and cholesterol, in this fusion process. Structural information from specular neutron reflectometry and small angle neutron scattering, complemented by dynamics information from quasi-elastic and spin-echo neutron spectroscopy, revealed strikingly different functions encoded in the Spike fusion domain. Calcium drives the N-terminal of the Spike fusion domain to fully cross the host plasma membrane. Removing calcium however re-orients the protein to the lipid leaflet in contact with the virus, leading to significant changes in lipid fluidity and rigidity. In conjunction with other regions of the fusion domain which are also positioned to bridge and dehydrate viral and host membranes, the molecular events leading to cell entry by SARS-CoV-2 are proposed.
  🖺 Full Text HTML: Strikingly different roles of SARS-CoV-2 fusion peptides uncovered by neutron scattering
• Relationship between COVID-19 infection and neurodegeneration: Computational insight into interactions between the SARS-CoV-2 spike protein and the monoamine oxidase enzymes -
  Although COVID-19 has been primarily associated with pneumonia, recent data show that its causative agent, the SARS-CoV-2 coronavirus, can infect many vital organs beyond the lungs, including the heart, kidneys and the brain. The literature agrees that COVID-19 is likely to have long-term mental health effects on infected individuals, which signifies a need to understand the role of the virus in the pathophysiology of brain disorders that is currently unknown and widely debated. Our docking and molecular dynamic simulations show that the affinity of the spike protein from the wild type (WT) and the South African B.1.351 (SA) variant towards the MAO enzymes is comparable to that for its ACE2 receptor. This allows for the WT/SA***MAO complex formation, which changes MAO affinities for their neurotransmitter substrates, thus consequently impacting the rates of their metabolic conversion and misbalancing their levels. Knowing that this fine regulation is strongly linked with the etiology of various brain pathologies, these results are the first to highlight the possibility that the interference with the brain MAO catalytic activity is responsible for the increased neurodegenerative illnesses following a COVID-19 infection, thus placing a neurobiological link between these two conditions in the spotlight. Since the obtained insight suggests that a more contagious SA variant causes even larger disturbances, and with new and more problematic strains likely emerging in the near future, we firmly advise that the presented prospect of the SARS-CoV-2 induced neurological complications should not be ignored, but rather requires further clinical investigations to achieve an early diagnosis and timely therapeutic interventions.
  🖺 Full Text HTML: Relationship between COVID-19 infection and neurodegeneration: Computational insight into interactions between the SARS-CoV-2 spike protein and the monoamine oxidase enzymes
• Epistasis at the SARS-CoV-2 RBD Interface and the Propitiously Boring Implications for Vaccine Escape -
  At the time of this writing, August 2021, potential emergence of vaccine escape variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a grave global concern. The interface between the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein and the host receptor (ACE2) overlap with the binding site of principal neutralizing antibodies (NAb), limiting the repertoire of viable mutations. Nonetheless, variants with multiple mutations in the RBD have rose to dominance. Non-additive, epistatic relationships among RBD mutations are apparent, and assessing the impact of such epistasis on the mutational landscape is crucial. Epistasis can substantially increase the risk of vaccine escape and cannot be completely characterized through the study of the wild type (WT) alone. We employed protein structure modeling using Rosetta to compare the effects of all single mutants at the RBD-NAb and RBD- ACE2 interfaces for the WT, Gamma (417T, 484K, 501Y), and Delta variants (452R, 478K). Overall, epistasis at the RBD surface appears to be limited and the effects of most multiple mutations are additive. Epistasis at the Delta variant interface weakly stabilizes NAb interaction relative to ACE2, whereas in the Gamma variant, epistasis more substantially destabilizes NAb interaction. These results suggest that the repertoire of potential escape mutations for the Delta variant is not substantially different from that of the WT, whereas Gamma poses a moderately greater risk for enhanced vaccine escape. Thus, the modest ensemble of mutations relative to the WT shown to reduce vaccine efficacy might constitute the majority of all possible escape mutations.
  🖺 Full Text HTML: Epistasis at the SARS-CoV-2 RBD Interface and the Propitiously Boring Implications for Vaccine Escape
• When Knowledge is Blinding: The Dangers of Being Certain About the Future -
  Despite much research on certainty and future thought, it remains unclear how certainty about the future influences the ways people think, feel, and act. Three studies (N = 1218) examined how certainty about the future impacts people’s cognition, affect, and behavior during two major events of future uncertainty; the COVID-19 pandemic and the 2020 U.S. Presidential Election. In Study 1, certainty about the future of COVID-19 predicted ignorance of medical information and lower objective knowledge about the virus. In line with these findings, in Study 2, certainty about the future of COVID-19 predicted endorsing riskier health behaviors. Turning to the 2020 Presidential Election, in Study 3, being certain that one’s preferred candidate would win the election predicted greater claims that the election was rigged (after the election) and identifying with Capitol insurrectionists. These findings introduce certainty about the future as a psychological phenomenon that entails intellectual blindness across diverging domains.
  🖺 Full Text HTML: When Knowledge is Blinding: The Dangers of Being Certain About the Future
• COVID-19 associated discrimination in Germany: Realistic and symbolic threats -
  The contribution focusses on Covid-19 associated discrimination (CAD) in Germany and asks whether immigrants from Asian origin are increasingly discriminated against during the COVID-19 pandemic and whether other immigrant groups face similar threats. Using data from the COVID-19 add-on-survey for CILS4EU-DE (CILS4COVID), we demonstrate that immigrants from Asian origin report an increasing CAD during the pandemic, which is more pronounced for respondents residing in administrative districts with a more dynamic COVID-19 situation. Similar results can be found for respondents originating from both American continents and from countries of the former Soviet Union. Given that COVID-19 was first reported in Asia, but with rather low number of infections later on, and the rather high infection rates on both American continents and in Russia, we conclude that CAD experienced by these groups might happen in a reaction to both realistic and symbolic threats posed by the virus.
  🖺 Full Text HTML: COVID-19 associated discrimination in Germany: Realistic and symbolic threats
• Inferring Transmission Fitness Advantage of SARS-CoV-2 Variants of Concern in Wastewater Using Digital PCR -

  Throughout the global COVID-19 pandemic, SARS-CoV-2 genetic variants of concern (VOCs) have repeatedly and independently arisen. VOCs are characterized by increased transmissibility, increased virulence, or reduced neutralization by antibodies obtained from prior infection or vaccination. Tracking the introduction and transmission of VOCs relies on sequencing, typically whole-genome sequencing of clinical samples. Wastewater surveillance is increasingly used to track the introduction and spread of SARS-CoV-2 variants through sequencing approaches. Here, we adapt and apply a rapid, high-throughput method for detection and quantification of the frequency of two deletions characteristic of the B.1.1.7, B.1.351, and P.1 VOCs in wastewater. We further develop a statistical approach to analyze temporal dynamics in drop-off RT-dPCR assay data to quantify transmission fitness advantage, providing data similar to that obtained from clinical samples. Digital PCR assays targeting signature mutations in wastewater offer near real-time monitoring of SARS-CoV-2 VOCs and potentially earlier detection and inference on transmission fitness advantage than clinical sequencing.

  🖺 Full Text HTML: Inferring Transmission Fitness Advantage of SARS-CoV-2 Variants of Concern in Wastewater Using Digital PCR
• Cultural Consumption and Covid-19: Evidence from the Taking Part and COVID-19 Cultural Participation Monitor surveys -
  How did cultural consumption change during the Covid-19 pandemic? Whilst the impact of the pandemic on cultural production has been given significant attention, work on consumption has seen less attention (Roberts 2020 on leisure time notwithstanding). This paper addresses this gap in the literature by presenting a comparative analysis of two, nationally representative, surveys of cultural activity in England. The analysis demonstrates that, when cultural consumption moved online and to digital modes of delivery and engagement as a result of the pandemic, there was no discernible transformation in the stratification of cultural participation in England. The majority of the population, characterised by the absence of participation in formal, and often state-funded, cultural forms, saw no change to their patterns of engagement. Where cultural consumption did increase, this was among the small minority of people who were already highly engaged. This minority maps closely onto pre-existing inequalities identified by existing research on cultural consumption, in England and beyond. For cultural consumption and the stratification of taste, it seems that the ‘new normal’ of pandemic life was much like the ‘old normal’ of an art and cultural audience characterised by significant inequality.
  🖺 Full Text HTML: Cultural Consumption and Covid-19: Evidence from the Taking Part and COVID-19 Cultural Participation Monitor surveys
• The People’s Vaccine: Intellectual Property, Access to Essential Medicines, and the Coronavirus COVID-19 -
  This paper explores intellectual property and access to essential medicines in the context of the coronavirus COVID-19 public health crisis. It considers policy solutions to counteract vaccine nationalism and profiteering by pharmaceutical companies and vaccine developers. This paper considers the campaign for the development of a People’s Vaccine led by the People’s Vaccine Alliance, UNAIDS, Oxfam and Public Citizen. The WHO has established the ACT Accelerator in order to boost research, development, and deployment of COVID-19 technologies. However, the operation of COVAX thus far has been falling short of its original ambitions. The Medicines Patent Pool has expanded its jurisdiction to include the sharing of intellectual property related to COVID-19. Meanwhile, Costa Rica has proposed a COVID-19 Technology Access Pool – an idea for a new institutional structure which has been taken up by the WHO. In the context of the coronavirus public health crisis, there has also been discussion of the use of compulsory licensing and crown use to counteract profiteering and anti-competitive behavior. There has been a push by Universities Allied for Essential Medicines (UAEM) and others for the public licensing of COVID-19 technologies developed with government funding. The Open COVID Pledge has been taken by a number of intellectual property owners. In response to the assertion of proprietary rights in respect of COVID-19 technologies, the open movement has championed the development of Open Science models of science. India and South Africa have put forward a waiver proposal in the TRIPS Council to enable countries to take action in respect of COVID-19 without fear of retribution under trade laws. While the United States has been willing to support a TRIPS Waiver for vaccines, there remain a number of opponents to a TRIPS Waiver – including the European Union, Germany, Japan, and Switzerland. This paper makes the case that international intellectual property law should accommodate a People’s Vaccine.
  🖺 Full Text HTML: The People’s Vaccine: Intellectual Property, Access to Essential Medicines, and the Coronavirus COVID-19
• Localized and Whole-Room Effects of Portable Air Filtration Units on Aerosol Particle Deposition and Concentration in a Classroom Environment -

  In indoor environments with limited ventilation, recirculating portable air filtration (PAF) units may reduce COVID-19 infection risk via not only the direct aerosol route (i.e., inhalation) but also via an indirect aerosol route (i.e., contact with the surface where particles deposited). We systematically investigated the impact of PAF units in a mock classroom, as a supplement to background ventilation, on localized and whole-room surface deposition and particle concentration. Fluorescently tagged particles with a volumetric mean diameter near two micrometers were continuously introduced into the classroom environment via a breathing simulator with a prescibed inhalation-exhalation waveform. Deposition velocities were inferred on >50 horizontal and vertical surfaces throughout the classroom, while aerosol concentrations were spatially monitored via optical particle spectrometry. Results revealed a particle decay rate consistent with expectations based upon the reported clean air delivery rates of the PAF units. Additionally, the PAF units reduced peak concentrations by a factor of around 2.5 compared to the highest concentrations observed and led to a statistically significant reduction in deposition velocities for horizontal surfaces >2.5 m from the aerosol source. Our results not only confirm PAF units can reduce particle concentrations but also demonstrate that they may lead to reduced particle deposition throughout an indoor environment when properly positioned.

  🖺 Full Text HTML: Localized and Whole-Room Effects of Portable Air Filtration Units on Aerosol Particle Deposition and Concentration in a Classroom Environment
• National Excess Mortality from Sub-National data: Method and Application for Argentina -

  Currently, many countries have not yet reported 2020 or 2021 mortality data to allow an estimate of excess mortality during the COVID-19 pandemic. However, some countries have sub-national mortality data, at the state, province or city level. I present a simple method to allow estimation of national level mortality and excess mortality from sub- national data, using the case of Argentina and projecting excess mortality up to July 2021.

  🖺 Full Text HTML: National Excess Mortality from Sub- National data: Method and Application for Argentina
• Waning immunity of the BNT162b2 vaccine: A nationwide study from Israel -

  Background: Starting December 2020, Israel began a mass vaccination campaign against coronavirus administering the Pfizer BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no SARS-CoV-2 infections, a resurgent COVID-19 outbreak initiated mid June 2021. Possible reasons for the breakthrough were reduced vaccine effectiveness against the Delta variant, and waning immunity. The aim of this study was to quantify the extent of waning immunity using Israel national-database. Methods: Data on all PCR positive test results between July 11-31, 2021 of Israeli residents who became fully vaccinated before June 2021 were used in this analysis. Infection rates and severe COVID-19 outcomes were compared between individuals who were vaccinated in different time periods using a Poisson regression, stratifying by age group and adjusting for possible confounding factors. Results: The rates of both documented SARS-CoV-2 infections and severe COVID-19 exhibit a statistically significant increase as time from second vaccine dose elapsed. Elderly individuals (60+) who received their second dose in March 2021 were 1.6 (CI: [1.3, 2]) times more protected against infection and 1.7 (CI: [1.0, 2.7]) times more protected against severe COVID-19 compared to those who received their second dose in January 2021. Similar results were found for different age groups. Conclusions: These results indicate a strong effect of waning immunity in all age groups after six months. Quantifying the effect of waning immunity on vaccine effectiveness is critical for policy makers worldwide facing the dilemma of administering booster vaccinations.

  🖺 Full Text HTML: Waning immunity of the BNT162b2 vaccine: A nationwide study from Israel
• Barrier gesture relaxation during vaccination campaign in France: modelling impact of waning immunity -

  Non-pharmaceutical interventions have been implemented intermittently for more than a year in most countries of the world to mitigate COVID-19 epidemic. In France, while the vaccination campaign is progressing, the French government has decided to remove many public health restrictions such as business closure, lockdowns and curfews. Nonetheless, social distancing, mask wearing, and hand washing (also called barrier gestures) are still recommended. We utilize an age-structured compartmental SEIR model that takes into account SARS-CoV-2 waning immunity, vaccination, and increased transmissibility from variants of concern, to estimate if barrier gestures can be relaxed without causing a resurgence of severe infections. This model assumes that susceptibility to infection is a function of immunity status, which depends on initial infection severity and vaccination status. It is calibrated on confirmed COVID-19 cases from the French surveillance database, and accounts for changes in contact behaviors due to implementation of nation-wide public health policies. We study partial and full relaxation of barrier gestures occurring from August to December 2021 under various immunity duration assumptions. Maintaining application of barrier gestures appears essential to avoid a resurgence of severe infections that would exceed health care capacities, while surmounting vaccine hesitancy represents the key to consider their relaxation. Immunity duration assumptions significantly influence the short-term dynamic of the epidemic which should be considered for further modelling.

  🖺 Full Text HTML: Barrier gesture relaxation during vaccination campaign in France: modelling impact of waning immunity

From Clinical Trials

• A Phase III Study to Evaluate the Efficacy and Safety of Proxalutamide (GT0918) in Hospitalized Subjects With COVID-19 - Condition:   Covid19
  Interventions:   Drug: GT0918;   Drug: Standard of care;   Drug: Matching placebo
  Sponsor:   Suzhou Kintor Pharmaceutical Inc,
  Not yet recruiting

• A Study of PF-07321332/Ritonavir in Non-hospitalized Low-Risk Adult Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PF-07321332;   Drug: Ritonavir;   Drug: Placebo
  Sponsor:   Pfizer
  Not yet recruiting

• Developing and Testing a COVID-19 Vaccination Acceptance Intervention - Condition:   COVID-19 Vaccination
  Intervention:   Behavioral: Moving to COVID-19 Vaccine Acceptance Intervention
  Sponsors:   VA Office of Research and Development;   VA Bedford Healthcare System
  Not yet recruiting

• Andrographis Paniculata vs Boesenbergia Rotunda vs Control in Asymptomatic COVID-19 - Condition:   Covid19
  Interventions:   Drug: Andrographis Paniculata;   Drug: Boesenbergia;   Other: Standard supportive treatment
  Sponsors:   Mahidol University;   Ministry of Health, Thailand
  Not yet recruiting

• Efficacy of PJS-539 for Adult Patients With COVID-19. - Conditions:   Covid19;   COVID-19 Pneumonia
  Interventions:   Drug: PJS-539 Dose 1;   Drug: PJS-539 Dose 2;   Drug: Placebo
  Sponsors:   Hospital do Coracao;   Covicept
  Not yet recruiting

• Enhancing COVID Rehabilitation With Technology - Condition:   Covid19
  Interventions:   Behavioral: NexJ Connected Wellness;   Other: Usual Care
  Sponsors:   University of Ottawa;   Canadian Institutes of Health Research (CIHR);   Ottawa Hospital Research Institute
  Not yet recruiting

• Phase I/II Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells) in Children and Adolescents - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Other: Placebo control
  Sponsors:   WestVac Biopharma Co., Ltd.;   West China Hospital
  Not yet recruiting

• Treatment of Covid-19 With a Herbal Compound, Xagrotin - Condition:   Covid19
  Intervention:   Combination Product: Xagrotin
  Sponsors:  
  Biomad AS;   Directorate of health of Sulaimani, Iraq -KRG
  Completed

• Philippine Trial to Determine Efficacy and Safety of Favipiravir for COVID-19 - Condition:   Covid19
  Interventions:   Combination Product: Favipiravir + Standard of Care;   Procedure: Standard of Care
  Sponsors:   University of the Philippines;   Department of Health, Philippines
  Recruiting

• Evaluation of the Effects of Bradykinin Antagonists on Pulmonary Manifestations of COVID-19 Infections (AntagoBrad- Cov Study). - Condition:   Covid19
  Interventions:   Drug: C1 Inhibitor Human;   Drug: Icatibant Injection;   Other: Placebo
  Sponsor:   GCS Ramsay Santé pour l’Enseignement et la Recherche
  Completed

• Combination of Dietary Supplements Curcumin, Quercetin and Vitamin D for Early Symptoms of COVID-19 - Condition:   Covid19
  Interventions:   Drug: Standard of care;   Dietary Supplement: combination of curcumin, quercetin and Vitamin D
  Sponsor:   Ayub Teaching Hospital
  Not yet recruiting

• Evaluation of Safety and Immunogenicity of a Novel Vaccine for Prevention of Covid-19 in Adults Previously Immunized - Condition:   Covid19
  Intervention:   Biological: A vaccine composed of a recombinant S1 antigen
  Sponsors:   Hospital do Coracao;   Farmacore Biotecnologia Ltda
  Withdrawn

• Phase 3 Clinical Study Evaluating Nitric Oxide Nasal Spray (NONS) Efficacy To Treat and Prevent the Exacerbation of Infection in Individuals With Documented Asymptomatic or Mild COVID-19 - Condition:   Covid19
  Intervention:   Drug: to be given as a treatment
  Sponsor:  
  Salmaniya Medical Complex
  Recruiting

• Changing of Prostate Specific Antigen Value in Patients With Covid-19 - Conditions:   Covid19;   Prostate Specific Antigen
  Intervention:   Other: PSA value
  Sponsor:   Saglik Bilimleri Universitesi
  Recruiting

• Evolution of Protective Immunization Against COVID-19 Among Hospital Workers in Health Care Facilities - Condition:   Covid19
  Intervention:   Other: Blood sample
  Sponsor:  
  Assistance Publique Hopitaux De Marseille
  Recruiting

From PubMed

• Updated pharmacological effects of Lonicerae japonicae flos, with a focus on its potential efficacy on coronavirus disease-2019 (COVID-19) - Lonicerae japonicae flos (LJF), known as Jin Yin Hua in Chinese, is one of the most commonly used traditional Chinese herbs and nutraceuticals. Nowadays, LJF is broadly applied in an array of afflictions, such as fever, sore throat, flu infection, cough, and arthritis, with the action mechanism to be elucidated. Here, we strove to summarize the main phytochemical components of LJF and review its updated pharmacological effects, including inhibition of inflammation, pyrexia, viruses, and…

• SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K/AKT/mTOR signaling - BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced inflammatory responses are largely responsible for the death of novel coronavirus disease 2019 (COVID-19) patients. However, the mechanism by which SARS-CoV-2 triggers inflammatory responses remains unclear. Here, we aimed to explore the regulatory role of SARS-CoV-2 spike protein in infected cells and attempted to elucidate the molecular mechanism of SARS-CoV-2-induced inflammation.

• An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis - Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), was the most significant infectious disease killer globally until the advent of COVID-19. Mtb has evolved to persist in its intracellular environment, evade host defenses, and has developed resistance to many anti-tubercular drugs. One approach to solving resistance is identifying existing approved drugs that will boost the host immune response to Mtb. These drugs could then be repurposed as adjunctive host-directed…

• The Use of Lectins as Tools to Combat SARS-CoV-2 - CONCLUSION: even with the development of effective vaccines, new cases of viral infection with the same virus, or new outbreaks with different viruses can occur; so, the development of new treatments should not be discarded. moreover, the discussions made in this work are relevant regarding the anti-viral properties of lectins.

• In vivo active organometallic-containing antimycotic agents - Fungal infections represent a global problem, notably for immunocompromised patients in hospital, COVID-19 patient wards and care home settings, and the ever-increasing emergence of multidrug resistant fungal strains is a sword of Damocles hanging over many healthcare systems. Azoles represent the mainstay of antifungal drugs, and their mode of action involves the binding mode of these molecules to the fungal lanosterol 14α-demethylase target enzyme. In this study, we have prepared and…

• A computational study on hydroxychloroquine binding to target proteins related to SARS-COV-2 infection - COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed a global health emergency. Repurposing of existing drugs can be a rapid and effective strategy to fight the infection. Clinical trials have reported reduction or elimination of viral load when patients were treated with the anti-malarial drug Hydroxychloroquine (HCQ). To understand the molecular mechanism of action for effective repurposing of this drug we have carried out in silico…

• Evaluation of a multi-species SARS-CoV-2 surrogate virus neutralization test - Assays to measure SARS-CoV-2-specific neutralizing antibodies are important to monitor seroprevalence, to study asymptomatic infections and to reveal (intermediate) hosts. A recently developed assay, the surrogate virus- neutralization test (sVNT) is a quick and commercially available alternative to the “gold standard” virus neutralization assay using authentic virus, and does not require processing at BSL-3 level. The assay relies on the inhibition of binding of the receptor binding domain (RBD)…

• Identification of Natural Inhibitors Against SARS-CoV-2 Drugable Targets Using Molecular Docking, Molecular Dynamics Simulation, and MM-PBSA Approach - The present study explores the SARS-CoV-2 drugable target inhibition efficacy of phytochemicals from Indian medicinal plants using molecular docking, molecular dynamics (MD) simulation, and MM-PBSA analysis. A total of 130 phytochemicals were screened against SARS-CoV-2 Spike (S)-protein, RNA-dependent RNA polymerase (RdRp), and Main protease (M^(pro)). Result of molecular docking showed that Isoquercetin potentially binds with the active site/protein binding site of the Spike, RdRP, and Mpro…

• An overview of potential inhibitors targeting non-structural proteins 3 (PL(pro) and Mac1) and 5 (3CL(pro)/M(pro)) of SARS-CoV-2 - There is an urgent need to develop effective treatments for the coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid spread of SARS-CoV-2 has resulted in a global pandemic that has not only affected the daily lives of individuals but also had a significant impact on the global economy and public health. Although extensive research has been conducted to identify inhibitors targeting SARS-CoV-2, there are still no effective…

• DAMPening COVID-19 Severity by Attenuating Danger Signals - COVID-19 might lead to multi-organ failure and, in some cases, to death. The COVID-19 severity is associated with a “cytokine storm.” Danger-associated molecular patterns (DAMPs) are proinflammatory molecules that can activate pattern recognition receptors, such as toll-like receptors (TLRs). DAMPs and TLRs have not received much attention in COVID-19 but can explain some of the gender-, weight- and age-dependent effects. In females and males, TLRs are differentially expressed, likely…

• In Silico Identification of MicroRNAs targeting the Key nucleator of Stress Granules, G3BP: Promising Therapeutics for SARS-CoV-2 Infection - Stress granules (SGs) are non-membrane ribonucleoprotein condensates formed in response to environmental stress conditions via liquid-liquid phase separation (LLPS). SGs are involved in the pathogenesis of aging and aging-associated diseases, cancers, viral infection, and several other diseases. GTPase-activating protein (SH3 domain)-binding protein 1 and 2 (G3BP1/2) is a key component and commonly used marker of SGs. Recent studies have shown that SARS-CoV-2 nucleocapsid protein via…

• In silico molecular docking of SARS-CoV-2 surface proteins with microbial non-ribosomal peptides: identification of potential drugs - Outbreak of COVID-19 by SARS-CoV-2 infection caused severe acute respiratory syndrome that has been declared a public health emergency of international concern. To control infections, there is urgent need to develop an effective therapeutic strategy. COVID-19 viral spike glycoprotein and proteases play major role in viral entry and mediating virus replication and spread and thus can serve as potential antiviral drug target. Being highly specific, efficacious and safe, peptides hold their place…

• In silico screening of FDA approved drugs against ACE2 receptor: potential therapeutics to inhibit the entry of SARS-CoV-2 to human cells - An unknown coronavirus that emerged sometime at the end of 2019 in China, the novel SARS-CoV-2, now called COVID-19, has spread all over the world. Several efforts have been made to prevent or treat this disease, though not with success. The initiation of COVID-19 viral infection involves specific binding of SARS-CoV-2 to the host surface of the receptor, ACE2. The ACE2- SARS-CoV-2 complex then gets transferred into the endosomes where the endosomal acidic proteases cleave the S protein present…

• Digital PCR can augment the interpretation of RT-qPCR Cq values for SARS-CoV-2 diagnostics - Coronavirus disease 2019 (COVID-19) is an infectious, acute respiratory disease caused mainly by person-to-person transmission of the coronavirus SARS-CoV-2. Its emergence has caused a world-wide acute health crisis, intensified by the challenge of reliably identifying individuals likely to transmit the disease. Diagnosis is hampered by the many unknowns surrounding this disease, including those relating to infectious viral burden. This uncertainty is exacerbated by disagreement surrounding the…

• In vitro data suggest that Indian variant B.1.617 of SARS-CoV-2 escapes neutralization by both receptor affinity and immune evasion - CONCLUSION: Our data suggest that the newly emerged SARS-CoV-2 variant B.1.617, as well as the better-studied variants B.1.351 and P.1 (all containing a mutation at position E484) display increased transmissibility both due their higher affinity for the cell receptor ACE2 and their ability to partially bypass immunity generated against the wild-type virus. For variant B.1.36 (with a point mutation at position N440), only increased affinity seems to play a role.

From Patent Search

• Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link

• SARS-COV-2 BINDING PROTEINS - - link

• A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS - - link

• IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION - - link

• Deep Learning Based System For Detection of Covid-19 Disease of Patient At Infection Risk. - - link

• 자외선살균등 - 본 발명은 사람의 의복이나 사용한 마스크 등에 부착하여 있다 호흡기로 유입되어 감염을 유발할 수 있는 COVID-19와 같은 유해균류를 간편하게 살균하기 위한 휴대용 자와선살균등에 관한 것이다. 반감기가 길고 인체에 유해한 오존을 발생하지 않으면서 탁월한 살균능력이 있는 250~265nm(최적은 253.7nm) 파장의 자외선을 발광하는 자외선램프를 본 발명의 막대형의 자외선살균등 광원으로 사용하고 비광원부를 손으로 잡고 의복이나 사용한 마스크 등 유해균류가 부착되었을 것으로 의심되는 곳에 자외선을 조사하여 간편하게 유해균류를 살균하므로써 감염을 예방하기 위한 휴대용 자외선살균등에 관함 것이다. - link

• Protein chip and kit for detecting the SARS-CoV-2 S antigen - - link

• 桑黄和百蕊草复方作为新型冠状病毒治疗药物或抗病毒制剂的用途 - 本发明公开了桑黄和百蕊草复方作为新型冠状病毒治疗药物或抗病毒制剂的用途。本发明提供了桑黄和百蕊草的应用：在制备治疗新型冠状病毒所致疾病的药物中的应用；在制备治疗新型冠状病毒感染的药物中的应用；在制备预防新型冠状病毒所致疾病的药物中的应用；在制备预防新型冠状病毒感染的药物中的应用；在制备新型冠状病毒抑制剂中的应用。发明人在前期研究发现桑黄和百蕊草具有抗新冠病毒的作用效果。进一步的，将百蕊草提取物与桑黄提取物组合使用，组合药物的毒性并没有增加，同时百蕊草有很强的抗炎作用，桑黄具有调节人体免疫力作用，这种组合药物对于治疗新冠肺炎病人是理想的选择药物。 - link