Covid-19 Sentry

Contents

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

From Preprints

• Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp3 Papain-like Protease -
  The COVID-19 pandemic has emerged as the biggest life-threatening disease of this century. Whilst vaccination should provide a long-term solution, this is pitted against the constant threat of mutations in the virus rendering the current vaccines less effective. Consequently, small molecule antiviral agents would be extremely useful to complement the vaccination program. The causative agent of COVID-19 is a novel coronavirus, SARS-CoV-2, which encodes at least nine enzymatic activities that all have drug targeting potential. The papain-like protease (PLpro) contained in the nsp3 protein generates viral non-structural proteins from a polyprotein precursor, and cleaves ubiquitin and ISG protein conjugates. Here we describe the expression and purification of PLpro. We developed a protease assay that was used to screen a custom chemical library from which we identified Dihydrotanshinone I and Ro 08-2750 as compounds that inhibit PLpro in protease and isopeptidase assays and also inhibit viral replication in cell culture-based assays.
  🖺 Full Text HTML: Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp3 Papain-like Protease
• Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of nsp5 Main Protease -
  The coronavirus 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread around the world with unprecedented health and socio-economic effects for the global population. While different vaccines are now being made available, very few antiviral drugs have been approved. The main viral protease (nsp5) of SARS-CoV-2 provides an excellent target for antivirals, due to its essential and conserved function in the viral replication cycle. We have expressed, purified and developed assays for nsp5 protease activity. We screened the nsp5 protease against a custom chemical library of over 5,000 characterised pharmaceuticals. We identified calpain inhibitor I and three different peptidyl fluoromethylketones (FMK) as inhibitors of nsp5 activity in vitro, with IC50 values in the low micromolar range. By altering the sequence of our peptidomimetic FMK inhibitors to better mimic the substrate sequence of nsp5, we generated an inhibitor with a subnanomolar IC50. Calpain inhibitor I inhibited viral infection in monkey-derived Vero E6 cells, with an EC50 in the low micromolar range. The most potent and commercially available peptidyl-FMK compound inhibited viral growth in Vero E6 cells to some extent, while our custom peptidyl FMK inhibitor offered a marked antiviral improvement.
  🖺 Full Text HTML: Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of nsp5 Main Protease
• Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp12/7/8 RNA-dependent RNA Polymerase -
  The coronavirus disease 2019 (COVID-19) global pandemic has turned into the largest public health and economic crisis in recent history impacting virtually all sectors of society. There is a need for effective therapeutics to battle the ongoing pandemic. Repurposing existing drugs with known pharmacological safety profiles is a fast and cost-effective approach to identify novel treatments. The COVID-19 etiologic agent is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded positive-sense RNA virus. Coronaviruses rely on the enzymatic activity of the replication-transcription complex (RTC) to multiply inside host cells. The RTC core catalytic component is the RNA-dependent RNA polymerase (RdRp) holoenzyme. The RdRp is one of the key druggable targets for CoVs due to its essential role in viral replication, high degree of sequence and structural conservation and the lack of homologs in human cells. Here, we have expressed, purified and biochemically characterised active SARS-CoV-2 RdRp complexes. We developed a novel fluorescence resonance energy transfer (FRET)-based strand displacement assay for monitoring SARS-CoV-2 RdRp activity suitable for a high-throughput format. As part of a larger research project to identify inhibitors for all the enzymatic activities encoded by SARS-CoV-2, we used this assay to screen a custom chemical library of over 5000 approved and investigational compounds for novel SARS-CoV-2 RdRp inhibitors. We identified 3 novel compounds (GSK-650394, C646 and BH3I-1) and confirmed suramin and suramin-like compounds as in vitro SARS-CoV-2 RdRp activity inhibitors. We also characterised the antiviral efficacy of these drugs in cell-based assays that we developed to monitor SARS-CoV-2 growth.
  🖺 Full Text HTML: Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp12/7/8 RNA-dependent RNA Polymerase
• Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp13 Helicase -
  The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there is a need for therapeutics. Repurposing existing drugs represents a promising and potentially rapid opportunity to find novel antivirals against SARS-CoV-2. The virus encodes at least nine enzymatic activities that are potential drug targets. Here we have expressed, purified and developed enzymatic assays for SARS-CoV-2 nsp13 helicase, a viral replication protein that is essential for the coronavirus life cycle. We screened a custom chemical library of over 5000 previously characterised pharmaceuticals for nsp13 inhibitors using a FRET-based high-throughput screening (HTS) approach. From this, we have identified FPA-124 and several suramin-related compounds as novel inhibitors of nsp13 helicase activity in vitro. We describe the efficacy of these drugs using assays we developed to monitor SARS-CoV-2 growth in Vero E6 cells.
  🖺 Full Text HTML: Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp13 Helicase
• Identification of SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of the nsp14 RNA Cap Methyltransferase -
  The COVID-19 pandemic has presented itself as one of the most critical public health challenges of the century, with SARS-CoV-2 being the third member of the Coronaviridae family to cause fatal disease in humans. There is currently only one antiviral compound, remdesivir, that can be used for the treatment of COVID-19. In order to identify additional potential therapeutics, we investigated the enzymatic proteins encoded in the SARS-CoV-2 genome. In this study, we focussed on the viral RNA cap methyltransferases, which play a key role in enabling viral protein translation and facilitating viral escape from the immune system. We expressed and purified both the guanine-N7 methyltransferase nsp14, and the nsp16 2-O-methyltransferase with its activating cofactor, nsp10. We performed an in vitro high-throughput screen for inhibitors of nsp14 using a custom compound library of over 5,000 pharmaceutical compounds that have previously been characterised in either clinical or basic research. We identified 4 compounds as potential inhibitors of nsp14, all of which also show antiviral capacity in a cell based model of SARS-CoV-2 infection. Three of the 4 compounds also exhibited synergistic effects on viral replication with remdesivir.
  🖺 Full Text HTML: Identification of SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of the nsp14 RNA Cap Methyltransferase
• Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp15 Endoribonuclease -
  SARS-CoV-2 is responsible for COVID-19, a human disease that has caused over 2 million deaths, stretched health systems to near-breaking point and endangered the economies of countries and families around the world. Antiviral treatments to combat COVID-19 are currently lacking. Remdesivir, the only antiviral drug approved for the treatment of COVID-19, can affect disease severity, but better treatments are needed. SARS-CoV-2 encodes 16 non-structural proteins (nsp) that possess different enzymatic activities with important roles in viral genome replication, transcription and host immune evasion. One key aspect of host immune evasion is performed by the uridine-directed endoribonuclease activity of nsp15. Here we describe the expression and purification of nsp15 recombinant protein. We have developed biochemical assays to follow its activity, and we have found evidence for allosteric behaviour. We screened a custom chemical library of over 5000 compounds to identify nsp15 endoribonuclease inhibitors, and we identified and validated NSC95397 as an inhibitor of nsp15 endoribonuclease in vitro. Although NSC95397 did not inhibit SARS-CoV-2 growth in VERO E6 cells, further studies will be required to determine the effect of nsp15 inhibition on host immune evasion.
  🖺 Full Text HTML: Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp15 Endoribonuclease
• Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp14/nsp10 Exoribonuclease -
  SARS-CoV-2 is a coronavirus that emerged in 2019 and rapidly spread across the world causing a deadly pandemic with tremendous social and economic costs. Healthcare systems worldwide are under great pressure, and there is urgent need for effective antiviral treatments. The only currently approved antiviral treatment for COVID-19 is remdesivir, an inhibitor of viral genome replication. SARS-CoV-2 proliferation relies on the enzymatic activities of the non-structural proteins (nsp), which makes them interesting targets for the development of new antiviral treatments. With the aim to identify novel SARS-CoV-2 antivirals, we have purified the exoribonuclease/methyltransferase (nsp14) and its cofactor (nsp10) and developed biochemical assays compatible with high-throughput approaches to screen for exoribonuclease inhibitors. We have screened a library of over 5000 commercial compounds and identified patulin and aurintricarboxylic acid (ATA) as inhibitors of nsp14 exoribonuclease in vitro. We found that patulin and ATA inhibit replication of SARS-CoV-2 in a VERO E6 cell-culture model. These two new antiviral compounds will be valuable tools for further coronavirus research as well as potentially contributing to new therapeutic opportunities for COVID-19.
  🖺 Full Text HTML: Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp14/nsp10 Exoribonuclease
• TMPRSS2 and RNA-dependent RNA polymerase are effective targets of therapeutic intervention for treatment of COVID-19 caused by SARS-CoV-2 variants (B.1.1.7 and B.1.351) -
  SARS-CoV-2 is a causative agent of COVID-19 pandemic and the development of therapeutic interventions is urgently needed. So far, monoclonal antibodies and drug repositioning are the main methods for drug development and this effort was partially successful. Since the beginning of COVID-19 pandemic, the emergence of SARS-CoV-2 variants has been reported in many parts of the world and the main concern is whether the current vaccines and therapeutics are still effective against these variant viruses. The viral entry and viral RNA-dependent RNA polymerase (RdRp) are the main targets of current drug development, thus the inhibitory effects of TMPRSS2 and RdRp inhibitors were compared among the early SARS-CoV-2 isolate (lineage A) and the two recent variants (lineage B.1.1.7 and lineage B.1.351) identified in the UK and South Africa, respectively. Our in vitro analysis of viral replication showed that the drugs targeting TMPRSS2 and RdRp are equally effective against the two variants of concern.
  🖺 Full Text HTML: TMPRSS2 and RNA-dependent RNA polymerase are effective targets of therapeutic intervention for treatment of COVID-19 caused by SARS-CoV-2 variants (B.1.1.7 and B.1.351)
• Antibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape -
  An ideal anti-SARS-CoV-2 antibody would resist viral escape, have activity against diverse SARS-related coronaviruses, and be highly protective through viral neutralization and effector functions. Understanding how these properties relate to each other and vary across epitopes would aid development of antibody therapeutics and guide vaccine design. Here, we comprehensively characterize escape, breadth, and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD), including S309, the parental antibody of the late-stage clinical antibody VIR-7831. We observe a tradeoff between SARS-CoV-2 in vitro neutralization potency and breadth of binding across SARS-related coronaviruses. Nevertheless, we identify several neutralizing antibodies with exceptional breadth and resistance to escape, including a new antibody (S2H97) that binds with high affinity to all SARS-related coronavirus clades via a unique RBD epitope centered on residue E516. S2H97 and other escape-resistant antibodies have high binding affinity and target functionally constrained RBD residues. We find that antibodies targeting the ACE2 receptor binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency, but we identify one potent RBM antibody (S2E12) with breadth across sarbecoviruses closely related to SARS-CoV-2 and with a high barrier to viral escape. These data highlight functional diversity among antibodies targeting the RBD and identify epitopes and features to prioritize for antibody and vaccine development against the current and potential future pandemics.
  🖺 Full Text HTML: Antibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape
• Functional evaluation of proteolytic activation for the SARS-CoV-2 variant B.1.1.7: role of the P681H mutation -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent behind the current COVID-19 pandemic having emerged in Wuhan China in late 2019 from a yet to be determined animal reservoir. SARS-CoV-2 B.1.1.7, a variant identified in the UK in late 2020, contains a higher than typical level of point mutants across its genome, including P681H in the spike S1/S2 cleavage site. Here, we performed assays using fluorogenic peptides mimicking the S1/S2 sequence from Wuhan-Hu1 and B.1.1.7 and observed no definitive difference in furin cleavage between Wuhan-Hu1 and B.1.1.7 in vitro. We performed functional assays using pseudo-typed particles harboring SARS-CoV-2 spike proteins and observed no significant differences between Wuhan-Hu1, Wuhan-Hu1 P681H or B.1.1.7 spike-carrying pseudo-typed particles in VeroE6 or Vero-TMPRSS2 cells, despite the spikes containing P681H being more efficiently cleaved. Likewise, we or show no differences in cell-cell fusion assays using the spike P681H-expressing cells. Our findings suggest that while the introduction of P681H in the SARS-CoV-2 B.1.1.7 variant may increase spike cleavage by furin-like proteases, this does not significantly impact viral entry or cell-cell spread. We consider that other factors are at play to account for the increased in transmission and disease severity attributed to this variant of concern (VOC).
  🖺 Full Text HTML: Functional evaluation of proteolytic activation for the SARS-CoV-2 variant B.1.1.7: role of the P681H mutation
• Comparable environmental stability and disinfection profiles of the currently circulating SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 -
  The emergence of novel SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern with increased transmission dynamics has raised questions regarding stability and disinfection of these viruses. In this study, we analyzed surface stability and disinfection of the currently circulating SARS-CoV-2 variants B.1.1.7 and B.1.351 compared to the wildtype. Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Furthermore, we observed comparable surface stability on steel, silver, copper and face masks. Overall, our data support the application of currently recommended hygiene concepts to minimize the risk of B.1.1.7 and B.1.351 transmission.
  🖺 Full Text HTML: Comparable environmental stability and disinfection profiles of the currently circulating SARS-CoV-2 variants of concern B.1.1.7 and B.1.351
• SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney -
  COVID-19 (coronavirus disease 2019) caused SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of mycarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).
  🖺 Full Text HTML: SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney
• Health Protocol Sanctions in Sorong Mayor Regulation Number 17 of 2020 -
  This study aims to analyze the legal sanctions for public health protocols in Article 7 of Sorong Mayor’s Regulation Number 17 of 2020. The type of research used in this study is a type of juridical normative research which is analyzed qualitatively with a statutory approach. The results of this study indicate that the sanctions in the form of monetary fines as stipulated in Article 7 paragraph (2) letter a do not have a firm legal basis, and tend to have the potential to disrupt economic activities to improve people’s welfare, especially in the era of the COVID-19 pandemic.
  🖺 Full Text HTML: Health Protocol Sanctions in Sorong Mayor Regulation Number 17 of 2020
• Network meta-analysis of interventions to prevent person-to-person transmission of SARS-CoV-2 and COVID-19 -
  The evidence on the relative ranking of effectiveness measures to prevent the SARS-CoV-2 spread from person to person is crucial for policy decision making. We have conducted the network meta-analysis by extending recent meta-analysis to delineate the relative effectiveness of different preventive measures. We observed properly used N95 respirator provides the best protection against SARS-CoV-2 in overall as well as healthcare set-up. In community settings, social distancing offers the best risk reduction against SARS-CoV-2.
  🖺 Full Text HTML: Network meta-analysis of interventions to prevent person-to-person transmission of SARS-CoV-2 and COVID-19
• The impact of the COVID-19 pandemic on gastrointestinal infection trends in England, February - July 2020 -

  Objective: To establish the impact of the first six months of the COVID-19 outbreak response of gastrointestinal (GI) infection trends in England. Design: Retrospective ecological study using routinely collected national and regional surveillance data from eight Public Health England coordinated laboratory, outbreak and syndromic surveillance systems using key dates of UK governmental policy change to assign phases for comparison between 2020 and historic data. Results: Decreases in GI illness activity were observed across all surveillance indicators as COVID-19 cases began to peak. Compared to the 5-year average (2015-2019), during the first six months of the COVD-19 response, there was a 52% decrease in GI outbreaks reported (1,544 vs. 3,208 (95% CI: 2,938 - 3,478) and a 34% decrease in laboratory confirmed cases (27,859 vs. 42,495 (95% CI: 40,068 - 44,922). GI indicators began to rise during the first lockdown and lockdown easing, although all remained substantially lower than historic figures. Reductions in laboratory confirmed cases were observed across all age groups and both sexes, with geographical heterogeneity observed in diagnosis trends. Health seeking behaviour changed substantially, with attendances decreasing prior to lockdown across all indicators. Conclusions: There has been a marked change in trends of GI infections in the context of the COVID-19 pandemic. The drivers of this change are likely to be multifactorial; while changes in health seeking behaviour, pressure on diagnostic services and surveillance system ascertainment have undoubtably played a role there has likely been a true decrease in the incidence for some pathogens resulting from the control measures and restrictions implemented. This suggests that if some of these changes in behaviour such as improved hand hygiene were maintained, then we could potentially see sustained reductions in the burden of GI illness.

  🖺 Full Text HTML: The impact of the COVID-19 pandemic on gastrointestinal infection trends in England, February - July 2020

From Clinical Trials

• Efficacy, Immunogenicity and Safety of Inactivated ERUCOV-VAC Compared With Placebo in COVID-19 - Condition:   COVID-19
  Interventions:   Biological: ERUCOV-VAC 3 µg/0.5 ml Vaccine;   Biological: ERUCOV-VAC 6 µg/0.5 ml Vaccine;   Other: Placebo
  Sponsors:   Health Institutes of Turkey;   Erciyes University Scientific Research Projects Coordination
  Recruiting

• A Nurse-Community Health Worker-Family Partnership Model: Addressing Uptake of COVID-19 Testing and Control Measures - Condition:   COVID-19
  Intervention:   Behavioral: Nurse-Community-Family Partnership Intervention
  Sponsor:   New York University
  Not yet recruiting

• A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ensovibep;   Drug: Placebo
  Sponsors:   Molecular Partners AG;   Novartis Pharmaceuticals;   Iqvia Pty Ltd;   Datamap;   SYNLAB Analytics & Services Switzerland AG;   Q2 Solutions
  Not yet recruiting

• Safety and Immunogenicity of the Inactivated Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine Compared to Placebo - Condition:   COVID-19 Vaccine
  Interventions:   Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 4 µg/0.5 ml Vaccine;   Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 6 µg/0.5 ml Vaccine;   Biological: Placebo
  Sponsor:   Kocak Farma
  Recruiting

• Study on Sequential Immunization of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine - Condition:   COVID-19
  Interventions:   Biological: recombinant Ad5 vectored COVID-19 vaccine;   Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19;   Biological: trivalent split influenza vaccine
  Sponsor:   Jiangsu Province Centers for Disease Control and Prevention
  Not yet recruiting

• Omega-3 Oil Use in COVID-19 Patients in Qatar - Condition:   COVID-19
  Intervention:   Drug: Omega 3 fatty acid
  Sponsor:   Hamad Medical Corporation
  Recruiting

• A Study to Test BI 767551 in People With Mild to Moderate Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: BI 767551 intravenous;   Drug: BI 767551 inhaled;   Drug: Placebo intravenous;   Drug: Placebo inhaled
  Sponsor:   Boehringer Ingelheim
  Not yet recruiting

• Tele-rehabilitation Program After Hospitalization for COVID-19 - Condition:   COVID-19 Pneumonia
  Interventions:   Other: TR;   Other: TSu
  Sponsors:   Istituti Clinici Scientifici Maugeri SpA;   Istituto Auxologico Italiano
  Recruiting

• The Effects of Web-Based Training for Covid-19 Patients on Symptom Management, Medication Compliance and Quality of Life - Condition:   COVID-19
  Intervention:   Other: intervention group
  Sponsor:   Eskisehir Osmangazi University
  Not yet recruiting

• ENO Breathe vs Usual Care in COVID-19 Recovery: An RCT - Condition:   COVID-19 Recovery
  Intervention:   Other: ENO Breathe group
  Sponsors:   Imperial College London;   Imperial College Healthcare NHS Trust
  Not yet recruiting

• SERUR: COVID-19 Serological Survey of Staff From the University Reims-Champagne Ardennes - Condition:   Covid19
  Intervention:   Diagnostic Test: Anti-SARS-CoV2 Serology
  Sponsor:   Université de Reims Champagne-Ardenne
  Completed

• Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Lyophilized Formulation 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

• Rehabilitation for Patients With Persistent Symptoms Post COVID-19 - Condition:   Covid19
  Intervention:   Other: Concentrated rehabilitation for patients with persistent symptoms post COVID-19
  Sponsors:   Western Norway University of Applied Sciences;   Helse-Bergen HF
  Recruiting

• Study of DS-5670a (COVID-19 Vaccine) in Japanese Healthy Adults and Elderly Subjects - Condition:   Covid19
  Interventions:   Biological: DS-5670a;   Biological: Placebo
  Sponsor:   Daiichi Sankyo Co., Ltd.
  Recruiting

• Study to Evaluate the Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate Against COVID-19 in Healthy Children <12 Years of Age - Condition:   SARS-CoV-2 Infection, COVID-19
  Interventions:   Biological: Biological/Vaccine: BNT162b2 10mcg;   Biological: BNT162b2 20mcg;   Biological: BNT162b2 30mcg
  Sponsors:   BioNTech SE;   Pfizer
  Recruiting

From PubMed

• ORF10-Cullin-2-ZYG11B complex is not required for SARS-CoV-2 infection - In order to understand the transmission and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to understand the functions of each of the gene products encoded in the viral genome. One feature of the SARS-CoV-2 genome that is not present in related, common coronaviruses is ORF10, a putative 38-amino acid protein-coding gene. Proteomic studies found that ORF10 binds to an E3 ubiquitin ligase containing Cullin-2, Rbx1, Elongin B, Elongin C, and ZYG11B…

• SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation - Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly…

• Drugs that inhibit TMEM16 proteins block SARS-CoV-2 Spike-induced syncytia - COVID-19 is a disease with unique characteristics including lung thrombosis¹, frequent diarrhoea², abnormal activation of the inflammatory response³ and rapid deterioration of lung function consistent with alveolar oedema⁴. The pathological substrate for these findings remains elusive. Here we show that the lungs of patients with COVID-19 contain infected pneumocytes with abnormal morphology and frequent multinucleation. Generation of these syncytia results from activation of the SARS-CoV-2…

• Identification of doxorubicin as a potential therapeutic against SARS-CoV-2 (COVID-19) protease: a molecular docking and dynamics simulation studies - After one year, the COVID-19 pandemic caused by SARS-CoV-2 is still the largest concern for the scientific community. Of the many recognized drug targets of SARS-CoV-2, the main protease is one of the most important target due to its function in viral replication. We conducted an in silico study with repurposing drugs of antibiotics class against virus protease and peptidase using AutoDock tool. The following significant binding energy interaction was observed with protease (PDB: 6LU7) like…

• Biomarkers of coagulation, endothelial function and fibrinolysis in critically-ill patients with COVID-19: A single-centre prospective longitudinal study - CONCLUSIONS: Longitudinal trajectories of clot lysis time, sTM, PAI-1, and plasminogen may have predictive ability for mortality in COVID-19.

• Pharmacokinetic and Pharmacodynamic Evaluation of Ravulizumab in Adults with Severe Coronavirus Disease 2019 - CONCLUSION: High levels of baseline C5 observed in patients with severe COVID-19 contribute to the growing body of evidence that suggests this disease is marked by amplification of terminal complement activation. Data from this preliminary pharmacokinetic/pharmacodynamic evaluation of 22 patients with severe COVID-19 show that the modified ravulizumab dosing regimen achieved immediate and complete terminal complement inhibition, which can be sustained for up to 22 days. These data support the…

• Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro - CONCLUSION AND IMPLICATIONS: Itraconazole-remdesivir and fluoxetine-remdesivir combinations are promising starting points for therapeutic options to control SARS-CoV-2 infection and severe progression of COVID-19.

• Vitamin D is a potential inhibitor of COVID-19: In silico molecular docking to the binding site of SARS-CoV-2 endoribonuclease Nsp15 - Novel coronavirus disease (COVID-19) has become a pandemic threat to public health. Vaccines and targeted therapeutics to prevent infections and stop virus proliferation are currently lacking. Endoribonuclease Nsp15 plays a vital role in the life cycle, including replication and transcription as well as virulence of the virus. Here, we investigated Vitamin D for its in silico potential inhibition of the binding sites of SARS-CoV-2 endoribonuclease Nsp15. In this study, we selected Remdesivir,…

• Virtual high throughput screening: Potential Inhibitors for SARS-CoV-2 PL(PRO) and 3CL(PRO) Proteases - The pandemic, COVID-19, has spread worldwide and affected millions of people. There is an urgent need, therefore, to find a proper treatment for the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent. This paper focuses on identifying inhibitors that target SARS-CoV-2 proteases, PL^(PRO) and 3CL^(PRO), which control the duplication and manages the life cycle of SARS-CoV-2. We have carried out detailed in silico Virtual high-throughput screening…

• Evidence that Maackia amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells with potential to inhibit SARS-CoV-2 infection and COVID-19 disease progression - COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 23 million confirmed COVID-19 cases that have cause over 800 thousand deaths worldwide as of August 19th, 2020. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface “spike” protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2…

• A novel anti-human IL-1R7 antibody reduces IL-18-mediated inflammatory signaling - Unchecked inflammation can result in severe diseases with high mortality, such as macrophage activation syndrome (MAS). MAS and associated cytokine storms have been observed in COVID-19 patients exhibiting systemic hyper-inflammation. Interleukin-18 (IL-18), a proinflammatory cytokine belonging to the IL-1 family, is elevated in both MAS and COVID-19 patients, and its level is known to correlate with the severity of COVID-19 symptoms. IL-18 binds its specific receptor IL-1 Receptor 5 (IL-1R5,…

• Silibinin as potential tool against SARS-Cov-2: In silico spike receptor-binding domain and main protease molecular docking analysis, and in vitro endothelial protective effects - The spread of SARS-CoV-2, along with the lack of targeted medicaments, encouraged research of existing drugs for repurposing. The rapid response to SARS-CoV-2 infection comprises a complex interaction of cytokine storm, endothelial dysfunction, inflammation, and pathologic coagulation. Thus, active molecules targeting multiple steps in SARS-CoV-2 lifecycle are highly wanted. Herein we explored the in silico capability of silibinin from Silybum marianum to interact with the SARS-CoV-2 main target…

• Reply letter to: Inhibition of SARS-CoV-2 replication using calcineurin inhibitors: Are concentrations required clinically achievable? - No abstract

• Analysis of glycosylation and disulfide bonding of wild-type SARS-CoV-2 spike glycoprotein - The SARS-CoV-2 coronavirus, the etiologic agent of COVID-19, uses its spike (S) glycoprotein anchored in the viral membrane to enter host cells. The S glycoprotein is the major target for neutralizing antibodies elicited by natural infection and by vaccines. Approximately 35% of the SARS-CoV-2 S glycoprotein consists of carbohydrate, which can influence virus infectivity and susceptibility to antibody inhibition. We found that virus-like particles produced by coexpression of SARS-CoV-2 S, M, E…

• Coagulation factors directly cleave SARS-CoV-2 spike and enhance viral entry - Coagulopathy is recognized as a significant aspect of morbidity in COVID-19 patients. The clotting cascade is propagated by a series of proteases, including factor Xa and thrombin. Other host proteases, including TMPRSS2, are recognized to be important for cleavage activation of SARS-CoV-2 spike to promote viral entry. Using biochemical and cell-based assays, we demonstrate that factor Xa and thrombin can also directly cleave SARS-CoV-2 spike, enhancing viral entry. A drug-repurposing screen…

From Patent Search

• 5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link

• USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link

• Peptides and their use in diagnosis of SARS-CoV-2 infection - - link

• A PROCESS FOR SUCCESSFUL MANAGEMENT OF COVID 19 POSITIVE PATIENTS - - link

• IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2 - IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2Insilico screening of antimycobacterial natural compounds with the potential to directly inhibit SARS COV2 relates to the composition for treating SARS-COV-2 comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. The composition also treats treating SARS, Ebola, Hepatitis-B and Hepatitis–C comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. - link

• 一种用于检测新型冠状病毒COVID-19的引物组及试剂盒 - 本发明涉及生物技术领域，特别是涉及一种用于检测冠状病毒的引物组及试剂盒，所述引物组包括以下中的一对或多对：外侧引物对：所述外侧引物对包括如SEQ ID NO:1所示的上游引物F3和如SEQ ID NO:2所示的下游引物B3；内侧引物对：所述内侧引物对包括如SEQ ID NO:3所示的上游引物FIP和如SEQ ID NO:4所示的下游引物BIP；环引物对：所述环引物对包括如SEQ ID NO:5所示的上游引物LF和如SEQ ID NO:6所示的下游引物LB。试剂盒包括所述引物组。本发明在一个管中整合了RT‑LAMP和CRISPR，能依据两次颜色变化检测病毒和各种靶标核酸。 - link

• 新冠病毒中和性抗体检测试剂盒 - 本发明提供一种新冠病毒中和性抗体检测试剂盒。所述试剂盒基于BAS‑HTRF技术，主要包含：生物素标记的hACE2、新冠病毒棘突蛋白RBD‑Tag1、能量供体Streptavidin‑Eu cryptate、能量受体MAb Anti‑Tag1‑d2和新冠病毒中和性抗体。本发明将BAS和HTRF两种技术相结合，用于筛选新型冠状病毒中和性抗体，3小时内即可实现筛选，且操作简单，无需经过多次洗板过程。BAS和HTRF联用大大提升了反应灵敏度，且两种体系都能最大限度地减少非特异的干扰，适用于血清样品的检测。该方法可实现高通量检测，对解决大批量样品的新冠病毒中和性抗体的检测具有重要意义。 - link

• Infektionsschutzmaske -

  Infektionsschutzmaske (1) zum Schutz vor Übertragung von Infektionskrankheiten mit einer Außen - und einer Innenseite (2,3) sowie Haltemitteln (5) zum Befestigen der Infektionsschutzmaske (1) am Kopf eines Maskenträgers, dadurch gekennzeichnet, dass an der Infektionsschutzmaske (1) mindestens eine Testoberfläche (6) zum Nachweis von Auslösern einer Infektionskrankheit derart angeordnet ist, dass diese bei korrekt angelegter Infektionsschutzmaske (1) mit der Ausatemluft des Maskenträgers unmittelbar in Kontakt gelangt.

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• Sars-CoV-2 vaccine antigens - - link

• SARS-COV-2 BINDING PROTEINS - - link