Covid-19 Sentry

Contents

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

From Preprints

• Report2: Impact of Covid-19 on young people aged 13-24 in the UK- preliminary findings -
  A brief follow on report (for Report 1, see https://psyarxiv.com/uq4rn/). This report presents data on parents and their children's well being as a result of the COVID-19 pandemic from our adult survey study. In addition to presenting additional data showing a potentially significant increase in anxiety and depression in young people aged 13-24, as a consequence of COVID-19. Data collection for our Adult Study (Wave 2) took place between 22nd April and was ended on Friday, May 1st, here we report headline figures for the impact of Covid-19 on parents and their children. We have described our methods in a separate report (https://psyarxiv.com/wxe2n) and released two reports on our mental health outcomes from wave 1 (https://psyarxiv.com/hb6nq, https://psyarxiv.com/ydvc7).
  🖺 Full Text HTML: Report2: Impact of Covid-19 on young people aged 13-24 in the UK- preliminary findings
• SARS-CoV-2 infection of circulating immune cells is not responsible for virus dissemination in severe COVID-19 patients -
  In late 2019 a novel coronavirus (SARS-CoV-2) emerged, and has since caused a global pandemic. Understanding the pathogenesis of COVID-19 disease is necessary to inform development of therapeutics, and management of infected patients. Using scRNAseq of blood drawn from SARS-CoV-2 patients, we asked whether SARS-CoV-2 may exploit immune cells as a 'Trojan Horse' to disseminate and access multiple organ systems. Our data suggests that circulating cells are not actively infected with SARS-CoV-2, and do not appear to be a source of viral dissemination.
  🖺 Full Text HTML: SARS-CoV-2 infection of circulating immune cells is not responsible for virus dissemination in severe COVID-19 patients
• BRD2 inhibition blocks SARS-CoV-2 infection in vitro by reducing transcription of the host cell receptor ACE2 -
  SARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted an unbiased CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. We found that the protein BRD2 is an essential node in the cellular response to SARS-CoV-2 infection. BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clinical trials potently block endogenous ACE2 expression and SARS-CoV-2 infection of human cells. BRD2 also controls transcription of several other genes induced upon SARS-CoV-2 infection, including the interferon response, which in turn regulates ACE2 levels. It is possible that the previously reported interaction between the viral E protein and BRD2 evolved to manipulate the transcriptional host response during SARS-CoV-2 infection. Together, our results pinpoint BRD2 as a potent and essential regulator of the host response to SARS-CoV-2 infection and highlight the potential of BRD2 as a novel therapeutic target for COVID-19.
  🖺 Full Text HTML: BRD2 inhibition blocks SARS-CoV-2 infection in vitro by reducing transcription of the host cell receptor ACE2
• Sterically-Confined Rearrangements of SARS-CoV-2 Spike Protein Control Cell Invasion -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious, and transmission involves a series of processes that may be targeted by vaccines and therapeutics. During transmission, host cell invasion is controlled by a large-scale conformational change of the Spike protein. This conformational rearrangement leads to membrane fusion, which creates transmembrane pores through which the viral genome is passed to the host. During Spike-protein-mediated fusion, the fusion peptides must be released from the core of the protein and associate with the host membrane. Interestingly, the Spike protein possesses many post-translational modifications, in the form of branched glycans that flank the surface of the assembly. Despite the large number of glycosylation sites, until now, the specific role of glycans during cell invasion has been unclear. Here, we propose that glycosylation is needed to provide sufficient time for the fusion peptides to reach the host membrane, otherwise the viral particle would fail to enter the host. To understand this process, an all-atom model with simplified energetics was used to perform thousands of simulations in which the protein transitions between the prefusion and postfusion conformations. These simulations indicate that the steric composition of the glycans induces a pause during the Spike protein conformational change. We additionally show that this glycan-induced delay provides a critical opportunity for the fusion peptides to capture the host cell. This previously-unrecognized role of glycans reveals how the glycosylation state can regulate infectivity of this pervasive pathogen.
  🖺 Full Text HTML: Sterically-Confined Rearrangements of SARS-CoV-2 Spike Protein Control Cell Invasion
• Azithromycin Plus Zinc Sulfate Rapidly and Synergistically Suppresses IκBα-Mediated In Vitro Human Airway Cell ACE2 Expression for SARS-CoV-2 Entry -
  Large-scale efforts have been persistently undertaken for medical prophylaxis and treatment of COVID-19 disasters worldwide. A variety of novel viral spike protein-targeted vaccine preparations have recently been clinically distributed based on accelerated approval. We revisited the early but inconclusive clinical interest in the combination of azithromycin and zinc sulfate repurposing with safety advantages. In vitro proof of concept was provided for rapid and synergistic suppression of ACE2 expression following treatments in human airway cells, Calu-3 and H322M. The two representative ACE2-expressing human airway cells indicate the upper and lower respiratory tracts. Prophylactic and early therapeutic roles of azithromycin combined with zinc are proposed for virus cellular entry prevention potential bridging to effective antibody production.
  🖺 Full Text HTML: Azithromycin Plus Zinc Sulfate Rapidly and Synergistically Suppresses IκBα-Mediated In Vitro Human Airway Cell ACE2 Expression for SARS-CoV-2 Entry
• A trans-complementation system for SARS-CoV-2 -
  The biosafety level-3 (BSL-3) requirement to culture severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a bottleneck for research and countermeasure development. Here we report a trans-complementation system that produces single-round infectious SARS-CoV-2 that recapitulates authentic viral replication. We demonstrate that the single-round infectious SARS-CoV-2 can be used at BSL-2 laboratories for high-throughput neutralization and antiviral testing. The trans-complementation system consists of two components: a genomic viral RNA containing a deletion of ORF3 and envelope gene, and a producer cell line expressing the two deleted genes. Trans-complementation of the two components generates virions that can infect naive cells for only one round, but does not produce wild-type SARS-CoV-2. Hamsters and K18-hACE2 transgenic mice inoculated with the complementation-derived virions exhibited no detectable disease, even after intracranial inoculation with the highest possible dose. The results suggest that the trans-complementation platform can be safely used at BSL-2 laboratories for research and countermeasure development.
  🖺 Full Text HTML: A trans-complementation system for SARS-CoV-2
• Experimental re-infected cats do not transmit SARS-CoV-2 -
  SARS-CoV-2 is the causative agent of COVID-19 and responsible for the current global pandemic. We and others have previously demonstrated that cats are susceptible to SARS-CoV-2 infection and can efficiently transmit the virus to naive cats. Here, we address whether cats previously exposed to SARS-CoV-2 can be re-infected with SARS-CoV-2. In two independent studies, SARS-CoV-2-infected cats were re-challenged with SARS-CoV-2 at 21 days post primary challenge (DPC) and necropsies performed at 4, 7 and 14 days post-secondary challenge (DP2C). Sentinels were co-mingled with the re-challenged cats at 1 DP2C. Clinical signs were recorded, and nasal, oropharyngeal, and rectal swabs, blood, and serum were collected and tissues examined for histologic lesions. Viral RNA was transiently shed via the nasal, oropharyngeal and rectal cavities of the re-challenged cats. Viral RNA was detected in various tissues of re-challenged cats euthanized at 4 DP2C, mainly in the upper respiratory tract and lymphoid tissues, but less frequently and at lower levels in the lower respiratory tract when compared to primary SARS-CoV-2 challenged cats at 4 DPC. Histologic lesions that characterized primary SARS-CoV-2 infected cats at 4 DPC were absent in the re-challenged cats. Naive sentinels co-housed with the re-challenged cats did not shed virus or seroconvert. Together, our results indicate that cats previously infected with SARS-CoV-2 can be experimentally re-infected with SARS-CoV-2; however, the levels of virus shed was insufficient for transmission to co-housed naive sentinels. We conclude that SARS-CoV-2 infection in cats induces immune responses that provide partial, non-sterilizing immune protection against reinfection.
  🖺 Full Text HTML: Experimental re-infected cats do not transmit SARS-CoV-2
• Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions -
  SARS-CoV-2 has emerged as a major threat to global public health, resulting in global societal and economic disruptions. Here, we investigate the intramolecular and intermolecular RNA interactions of wildtype (WT) and a mutant ({Delta}382) SARS-CoV-2 virus in cells using high throughput structure probing on Illumina and Nanopore platforms. We identified twelve potentially functional structural elements within the SARS-CoV-2 genome, observed that identical sequences can fold into divergent structures on different subgenomic RNAs, and that WT and {Delta}382 virus genomes can fold differently. Proximity ligation sequencing experiments identified hundreds of intramolecular and intermolecular pair-wise interactions within the virus genome and between virus and host RNAs. SARS-CoV-2 binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2'-O-methylated. 2'-O-methylation sites in the virus genome are enriched in the untranslated regions and are associated with increased pair-wise interactions. SARS-CoV-2 infection results in a global decrease of 2'-O-methylation sites on host mRNAs, suggesting that binding to snoRNAs could be a pro-viral mechanism to sequester methylation machinery from host RNAs towards the virus genome. Collectively, these studies deepen our understanding of the molecular basis of SARS-CoV-2 pathogenicity, cellular factors important during infection and provide a platform for targeted therapy.
  🖺 Full Text HTML: Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions
• An all-solid-state heterojunction oxide transistor for the rapid detection of biomolecules and SARS-CoV-2 spike S1 protein -
  Solid-state transistor sensors that can detect biomolecules in real time are highly attractive for emerging bioanalytical applications. However, combining cost-effective manufacturing with high sensitivity, specificity and fast sensing response, remains challenging. Here we develop low-temperature solution-processed In2O3/ZnO heterojunction transistors featuring a geometrically engineered tri-channel architecture for rapid real-time detection of different biomolecules. The sensor combines a high electron mobility channel, attributed to the quasi-two-dimensional electron gas (q2DEG) at the buried In2O3/ZnO heterointerface, in close proximity to a sensing surface featuring tethered analyte receptors. The unusual tri-channel design enables strong coupling between the buried q2DEG and the minute electronic perturbations occurring during receptor-analyte interactions allowing for robust, real-time detection of biomolecules down to attomolar (aM) concentrations. By functionalizing the tri-channel surface with SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) antibody receptors, we demonstrate real-time detection of the SARS-CoV-2 spike S1 protein down to attomolar concentrations in under two minutes.
  🖺 Full Text HTML: An all-solid-state heterojunction oxide transistor for the rapid detection of biomolecules and SARS-CoV-2 spike S1 protein
• The impact of Spike mutations on SARS-CoV-2 neutralization -
  Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike. Antibodies from SARS-CoV-2 infection neutralize the virus by focused targeting of Spike and there is limited serum cross-neutralization of the closely-related SARS-CoV. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, 501Y.V2 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus or the current vaccines will remain effective against virus variants. In this study we evaluate neutralization of a series of mutated Spike pseudotypes including a B.1.1.7 Spike pseudotype. The analyses of a panel of Spike-specific monoclonal antibodies revealed that the neutralizing activity of some antibodies was dramatically reduced by Spike mutations. In contrast, polyclonal antibodies in the serum of patients infected in early 2020 remained active against most mutated Spike pseudotypes. The majority of serum samples were equally able to neutralize the B.1.1.7 Spike pseudotype, however potency was reduced in a small number of samples (3 of 36) by 5-10-fold. This work highlights that changes in the SARS-CoV-2 Spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.
  🖺 Full Text HTML: The impact of Spike mutations on SARS-CoV-2 neutralization
• The effect of eviction moratoria on the transmission of SARS-CoV-2 -

  Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here we model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical metropolitan area. We recreate a range of urban epidemic trajectories and project the course of the epidemic under two counterfactual scenarios, one in which a strict moratorium on evictions is in place and enforced, and another in which evictions are allowed to resume at baseline or increased rates. We find, across scenarios, that evictions lead to significant increases in infections. Applying our model to Philadelphia using locally-specific parameters shows that the increase is especially profound in models that consider realistically heterogenous cities in which both evictions and contacts occur more frequently in poorer neighborhoods. Our results provide a basis to assess municipal eviction moratoria and show that policies to stem evictions are a warranted and important component of COVID-19 control.

  🖺 Full Text HTML: The effect of eviction moratoria on the transmission of SARS-CoV-2
• Rapid protection from COVID-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine -
  The ongoing pandemic of Coronavirus disease 2019 (COVID-19) continues to exert a significant burden on health care systems worldwide. With limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against SARS-CoV-2. Here, we generated a single dose, fast-acting vesicular stomatitis virus-based vaccine derived from the licensed Ebola virus (EBOV) vaccine rVSV-ZEBOV, expressing the SARS-CoV-2 spike protein and the EBOV glycoprotein (VSV-SARS2-EBOV). Rhesus macaques vaccinated intramuscularly (IM) with a single dose of VSV-SARS2-EBOV were protected within 10 days and did not show signs of COVID-19 pneumonia. In contrast, IN vaccination resulted in limited immunogenicity and enhanced COVID-19 pneumonia compared to control animals. While IM and IN vaccination both induced neutralizing antibody titers, only IM vaccination resulted in a significant cellular immune response. RNA sequencing data bolstered these results by revealing robust activation of the innate and adaptive immune transcriptional signatures in the lungs of IM-vaccinated animals only. Overall, the data demonstrates that VSV-SARS2-EBOV is a potent single-dose COVID-19 vaccine candidate that offers rapid protection based on the protective efficacy observed in our study.
  🖺 Full Text HTML: Rapid protection from COVID-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine
• mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants -
  To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected nearly 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease-2019 (COVID-19) including two novel mRNA-based vaccines. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S), receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.
  🖺 Full Text HTML: mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
• Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera -
  Recently, a new SARS-CoV-2 lineage called B.1.1.7 has emerged in the United Kingdom that was reported to spread more efficiently than other strains. This variant has an unusually large number of mutations with 10 amino acid changes in the spike protein, raising concerns that its recognition by neutralizing antibodies may be affected. Here, we investigated SARS-CoV-2-S pseudoviruses bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein with sera of 16 participants in a previously reported trial with the mRNA-based COVID-19 vaccine BNT162b2. The immune sera had equivalent neutralizing titers to both variants. These data, together with the combined immunity involving humoral and cellular effectors induced by this vaccine, make it unlikely that the B.1.1.7 lineage will escape BNT162b2-mediated protection.
  🖺 Full Text HTML: Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera
• Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine -
  Vaccine development against the SARS-CoV-2 virus focuses on the principal target of the neutralizing immune response, the spike (S) glycoprotein. Adenovirus-vectored vaccines offer an effective platform for the delivery of viral antigen, but it is important for the generation of neutralizing antibodies that they produce appropriately processed and assembled viral antigen that mimics that observed on the SARS-CoV-2 virus. Here, we describe the structure, conformation and glycosylation of the S protein derived from the adenovirus-vectored ChAdOx1 nCoV-19/AZD1222 vaccine. We demonstrate native-like post-translational processing and assembly, and reveal the expression of S proteins on the surface of cells adopting the trimeric prefusion conformation. The data presented here confirms the use of ChAdOx1 adenovirus vectors as a leading platform technology for SARS-CoV-2 vaccines.
  🖺 Full Text HTML: Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine

From Clinical Trials

• APT™ T3X on the COVID-19 Contamination Rate - Condition:   COVID-19
  Interventions:   Drug: Tetracycline hydrochloride 3%;   Drug: Placebo
  Sponsors:   University of Nove de Julho;   Santa Casa de Misericórdia de Porto Alegre
  Not yet recruiting

• A Study of ORTD-1 in Patients Hospitalized With COVID-19 Related Pneumonia - Condition:   COVID-19
  Interventions:   Drug: ORTD-1 low dose;   Drug: ORTD-1 mid dose;   Drug: ORTD-1 high dose;   Other: Vehicle control
  Sponsor:   Oryn Therapeutics, LLC
  Recruiting

• Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Doxycycline Tablets;   Drug: Rivaroxaban 15Mg Tab;   Combination Product: Hydroxychloroquine and Azithromycin
  Sponsor:   Yaounde Central Hospital
  Recruiting

• The Effect of Deep Breathing Exercise on Dyspnea, Anxiety and Quality of Life in Patients Treated for COVID-19 - Condition:   COVID-19
  Intervention:   Behavioral: Deep Breathing Exercise with Triflo
  Sponsor:   Ankara University
  Not yet recruiting

• Pilot Study of Cefditoren Pivoxil in COVID-19 Patients With Mild to Moderate Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Cefditoren pivoxil 400mg
  Sponsor:   Meiji Pharma Spain S.A.
  Recruiting

• A Real World Study of Bamlanivimab in Participants With Mild-to-moderate Coronavirus Disease 2019 (COVID-19) - Condition:   COVID-19
  Intervention:   Drug: Bamlanivimab
  Sponsors:   Eli Lilly and Company;   AbCellera Biologics Inc.
  Not yet recruiting

• Study to Evaluate the Effects of AT-527 in Non-Hospitalized Adult Patients With Mild or Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: AT-527;   Drug: Placebo
  Sponsors:   Hoffmann-La Roche;   Atea Pharmaceuticals, Inc.
  Not yet recruiting

• Dexamethasone for COVID-19 - Condition:   Covid19
  Intervention:   Drug: Dexamethasone
  Sponsor:   University of Oklahoma
  Not yet recruiting

• Efficacy and Safety of DWJ1248 With Remdesivir in Severe COVID-19 Patients - Condition:   Severe COVID-19
  Interventions:   Drug: DWJ1248 with Remdesivir;   Drug: Placebo with Remdesivir
  Sponsor:   Daewoong Pharmaceutical Co. LTD.
  Not yet recruiting

• Assessment of Efficacy and Safety of Therapy With COVID-19 Convalescent Plasma in Subjects With Severe COVID-19 (IPCO) - Condition:   Severe COVID-19
  Intervention:   Biological: COVID-19 convalescent plasma
  Sponsor:   University of Erlangen-Nürnberg Medical School
  Recruiting

• Mesenchymal Stem Cells Therapy in Patients With COVID-19 Pneumonia - Condition:   Coronavirus Disease 2019 (COVID-19) Pneumonia
  Intervention:   Other: Mesenchymal stem cells
  Sponsor:   Kanuni Sultan Suleyman Training and Research Hospital
  Completed

• Study to Evaluate the Lot Consistency, Safety, Tolerability, and Immunogenicity of BNT162b2 Against COVID-19 in Healthy Adults - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Intervention:   Biological: BNT162b2
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• The (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial) - Condition:   Covid19
  Interventions:   Drug: Ivermectin 0.6mg/kg/day;   Drug: Ivermectin 1.0mg/kg/day;   Drug: Placebo;   Drug: Hydroxychloroquine
  Sponsor:   Corpometria Institute
  Not yet recruiting

• To Evaluate SCTA01 Treatment of High-risk Outpatients With COVID-19 - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Drug: SCTA01;   Other: Placebo
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Study of Adalimumab or Placebo in Patients With Mild to Moderate COVID-19 - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: Adalimumab;   Drug: Placebo
  Sponsors:   Ology Bioservices;   Pharm-Olam, LLC;   Chemical, Biological, Radiological, and Nuclear Medical
  Not yet recruiting

From PubMed

• Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2 - Hydroxychloroquine, used to treat malaria and some autoimmune disorders, potently inhibits viral infection of SARS coronavirus (SARS-CoV-1) and SARS-CoV-2 in cell-culture studies. However, human clinical trials of hydroxychloroquine failed to establish its usefulness as treatment for COVID-19. This compound is known to interfere with endosomal acidification necessary to the proteolytic activity of cathepsins. Following receptor binding and endocytosis, cathepsin L can cleave the SARS-CoV-1 and...

• Modeling the structure of the frameshift-stimulatory pseudoknot in SARS-CoV-2 reveals multiple possible conformers - The coronavirus causing the COVID-19 pandemic, SARS-CoV-2, uses -1 programmed ribosomal frameshifting (-1 PRF) to control the relative expression of viral proteins. As modulating -1 PRF can inhibit viral replication, the RNA pseudoknot stimulating -1 PRF may be a fruitful target for therapeutics treating COVID-19. We modeled the unusual 3-stem structure of the stimulatory pseudoknot of SARS-CoV-2 computationally, using multiple blind structural prediction tools followed by μs-long molecular...

• Fighting the storm: could novel anti-TNFalpha and anti-IL-6 C. sativa cultivars tame cytokine storm in COVID-19? - The main aspects of severe COVID-19 disease pathogenesis include hyper-induction of proinflammatory cytokines, also known as 'cytokine storm', that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There remains no effective treatment for these complications. Out of all cytokines, TNFα and IL-6 play crucial roles in cytokine storm pathogenesis and are likely responsible for the...

• Purinergic Signaling of ATP in COVID-19 Associated Guillain-Barre Syndrome - Declared as a global public health emergency, coronavirus disease 2019 (COVID-19) is presented as a disease of the respiratory tract, although severe cases can affect the entire organism. Several studies have shown neurological symptoms, ranging from dizziness and loss of consciousness to cerebrovascular and neurodegenerative diseases. In this context, Guillain-Barré syndrome, an immune-mediated inflammatory neuropathy, has been closely associated with critical cases of infection with "severe...

• Mass spectrometry reveals potential of beta-lactams as SARS-CoV-2 M(pro) inhibitors - The main viral protease (Mpro) of SARS-CoV-2 is a nucleophilic cysteine hydrolase and a current target for anti-viral chemotherapy. We describe a high-throughput solid phase extraction coupled to mass spectrometry Mpro assay. The results reveal some β-lactams, including penicillin esters, are active site reacting Mpro inhibitors, thus highlighting the potential of acylating agents for Mpro inhibition.

• Evaluation of the efficacy and safety of inhaled magnesium sulphate in combination with standard treatment in patients with moderate or severe COVID-19: A structured summary of a study protocol for a randomised controlled trial - OBJECTIVES: Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered...

• What coronavirus 3C-like protease tells us: From structure, substrate selectivity, to inhibitor design - The emergence of a variety of coronaviruses (CoVs) in the last decades has posed huge threats to human health. Especially, the ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 70 million infections and over 1.6 million of deaths worldwide in the past few months. None of the efficacious antiviral agents against human CoVs have been approved yet. 3C-like protease (3CL^(pro) ) is an attractive target...

• Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19 - We describe the cytokine profiles of a large cohort of hospitalized patients with moderate to critical COVID-19, focusing on IL-6, sIL2R, and IL-10 levels before and after receiving immune modulating therapies, namely, tocilizumab and glucocorticoids. We also discuss the possible roles of sIL2R and IL-10 as markers of ongoing immune dysregulation after IL-6 inhibition. We performed a retrospective chart review of adult patients admitted to a tertiary care center with moderate to critical...

• Natural agents modulating ACE-2: A review of compounds with potential against SARS-CoV-2 infections - One of the biggest challenges of public health worldwide is reducing the number of events and deaths related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The angiotensin-converting enzyme 2 (ACE2), a carboxypeptidase that degrades angiotensin II into angiotensin 1-7, has been identified as a potent receptor for SARSCoV-2. In the last decades, ACE inhibition has assumed a central role in reducing cardiovascular and renal events. However, with the advent of COVID-19,...

• An in silico analysis of Ibuprofen enantiomers in high concentrations of sodium chloride with SARS-CoV-2 main protease - 2020 will be remembered worldwide for the outbreak of Coronavirus disease (COVID-19), which quickly spread until it was declared as a global pandemic. The main protease (Mpro) of SARS-CoV-2, a key enzyme in coronavirus, represents an attractive pharmacological target for inhibition of SARS-CoV-2 replication. Here, we evaluated whether the anti-inflammatory drug Ibuprofen, may act as a potential SARS-CoV-2 Mpro inhibitor, using an in silico study. From molecular dynamics (MD) simulations, we also...

• Molecular docking and simulation studies of natural compounds of Vitex negundo L. against papain-like protease (PL(pro)) of SARS CoV-2 (coronavirus) to conquer the pandemic situation in the world - The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is β-coronavirus that is responsible for the pandemic coronavirus disease 2019 (COVID-19) all over the world. The rapid spread of the novel SARS CoV-2 worldwide is raising a significant global public health issue with nearly 61.86 million people infected and 1.4 million deaths. To date, no specific drugs are available for the treatment of COVID-19. The inhibition of proteases essential for the proteolytic treatment of viral...

• Withanolides from Withania somnifera as an immunity booster and their therapeutic options against COVID-19 - Traditionally, Withania somnifera is widely used as an immune booster, anti-viral, and for multiple medicinal purposes. The present study investigated the withanolides as an immune booster and anti-viral agents against the coronavirus-19. Withanolides from Withania somnifera were retrieved from the open-source database, their targets were predicted using DIGEP-Pred, and the protein-protein interaction was evaluated. The drug-likeness score and intestinal absorptivity of each compound were also...

• Potential health benefits of zinc supplementation for the management of COVID-19 pandemic - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the Coronavirus Disease 2019 (COVID-19). The COVID-19 pandemic has created unimaginable and unprecedented global health crisis. Since the outbreak of COVID-19, millions of dollars have been spent, hospitalization overstretched with increasing morbidity and mortality. All these have resulted in unprecedented global economic catastrophe. Several drugs and vaccines are currently being evaluated, tested,...

• Compounds of Citrus medica and Zingiber officinale for COVID-19 inhibition: in silico evidence for cues from Ayurveda - CONCLUSION: In silico studies suggest that the phytochemical compounds in C. medica and Z. officinale may have good potential in reducing viral load and shedding of SARS-CoV-2 in the nasal passages. Further studies are recommended to test its efficacy in humans for mitigating the transmission of COVID-19.

• Factual insights of the allosteric inhibition mechanism of SARS-CoV-2 main protease by quercetin: an in silico analysis - SARS-CoV-2 main protease (M^(pro)) cleaves the viral polypeptide 1a and 1ab in a site-specific ((L-Q|(S, A, G)) manner and produce functional enzymes for mediating viral replication. Numerous studies have reported synthetic competitive inhibitors against this target enzyme but increase in substrate concentration often reduces the effectiveness of such inhibitors. Allosteric inhibition by natural compound can provide safe and effective treatment by alleviating this limitation. Present study deals...

From Patent Search

• COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS - - link

• A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof - - link

• Covid 19 - Chewing Gum - - link

• STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19 - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - link

• Fahrzeuglüftungssystem und Verfahren zum Betreiben eines solchen Fahrzeuglüftungssystems -

  Die Erfindung betrifft ein Fahrzeuglüftungssystem (1) zum Belüften einer Fahrgastzelle (2) eines Fahrzeugs (3), mit einem Umluftpfad (5). Die Erfindung ist gekennzeichnet durch eine wenigstens abschnittsweise in einen Umluftansaugbereich (4) des Umluftpads (5) hineinreichende Sterilisationseinrichtung (6), wobei die Sterilisationseinrichtung (6) dazu eingerichtet ist von einem aus der Fahrgastzelle (2) entnommenen Luftstrom getragene Schadstoffe zu inaktivieren und/oder abzutöten.

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• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• "AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2." - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - link

• Mund-Nasen-Bedeckung -

  Mund-Nasen-Bedeckung (1), wobei die Mund-Nasen-Bedeckung (1) mindestens an einem Ohr eines Trägers magnetisch befestigbar ist.

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• Haptens, hapten conjugates, compositions thereof and method for their preparation and use - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - link