Covid-19 Sentry

Contents

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

From Preprints

• Elite Messaging and Social Exclusion Shapes Asian American Partisan Attitudes During Times of Pandemic -
  Extending theories of social exclusion and elite messaging, we argue that Trump’s targeted rhetoric toward Asian Americans during the COVID-19 pandemic pushes the racial group, largely “Independent” or nonpartisan affiliated, to lean more towards the Democratic Party. This article supports this claim by combining social media (Study 1) and survey data (Study 2) analysis. Tracing 1.4 million tweets, we find that Trump’s rhetoric has popularized racially charged coronavirus-related terms and that exclusionary, anti-Asian attitudes have increased in the U.S. since the pandemic began. Next, by analyzing repeated cross-sectional weekly surveys of Asian Americans from July 2019 to May 2020 (n=12,907), we find that the group has leaned more towards the Democratic Party since Trump first made inflammatory remarks towards Asian Americans. Whites, Blacks, and Latina/os, on the other hand, exhibited little and less consistent change in these democratic-related attitudes. Our findings suggest that experiences with social exclusion that are driven by elite sources further cement Asian Americans as Democrats.
  🖺 Full Text HTML: Elite Messaging and Social Exclusion Shapes Asian American Partisan Attitudes During Times of Pandemic
• Identification, crystallization and epitope determination of public TCR shared and expanded in COVID-19 patients -
  T cells play pivotal roles in protective immunity against SARS-CoV-2 infection. Follicular helper T (Tfh) cells mediate the production of antigen-specific antibodies; however, T cell receptor (TCR) clonotypes used by SARS-CoV-2-specific Tfh cells have not been well characterized. Here, we first identified and crystallized public TCR of Tfh clonotypes that are shared and expanded in unhospitalized COVID-19-recovered patients. These clonotypes preferentially recognized SARS-CoV-2 spike (S) protein epitopes which are conserved among emerging SARS-CoV-2 variants. These clonotypes did not react with S proteins derived from common cold human coronaviruses, but cross-reacted with symbiotic bacteria, which might confer the publicity. Among SARS-CoV-2 S epitopes, S864-882, presented by frequent HLA-DR alleles, could activate multiple public Tfh clonotypes in COVID-19-recovered patients. Furthermore, S864-882-loaded HLA tetramer preferentially bound to CD4+ T cells expressing CXCR5. In this study, we identified and crystallized public TCR for SARS-CoV-2 that may contribute to the prevention of COVID-19 aggravation.
  🖺 Full Text HTML: Identification, crystallization and epitope determination of public TCR shared and expanded in COVID-19 patients
• Clonal dissection of immunodominance and cross-reactivity of the CD4+ T cell response to SARS-CoV-2 -
  The identification of CD4+ T cell epitopes is essential for the design of effective vaccines capable of inducing neutralizing antibodies and long-term immunity. Here we demonstrate in COVID-19 patients a robust CD4+ T cell response to naturally processed SARS-CoV-2 Spike and Nucleoprotein, including effector, helper and memory T cells. By characterizing 2,943 Spike-reactive T cell clones, we found that 34% of the clones and 93% of the patients recognized a conserved immunodominant region encompassing residues S346-365 in the RBD and comprising three nested HLA-DR and HLA-DP restricted epitopes. By using pre- and post-COVID-19 samples and Spike proteins from alpha and beta coronaviruses, we provide in vivo evidence of cross-reactive T cell responses targeting multiple sites in the SARS-CoV-2 Spike protein. The possibility of leveraging immunodominant and cross-reactive T helper epitopes is instrumental for vaccination strategies that can be rapidly adapted to counteract emerging SARS-CoV-2 variants.
  🖺 Full Text HTML: Clonal dissection of immunodominance and cross-reactivity of the CD4+ T cell response to SARS-CoV-2
• Application of an integrated computational antibody engineering platform to design SARS-CoV-2 neutralizers -
  As the COVID-19 pandemic continues to spread, hundreds of new initiatives including studies on existing medicines are running to fight the disease. To deliver a potentially immediate and lasting treatment to current and emerging SARS-CoV-2 variants, new collaborations and ways of sharing are required to create as many paths forward as possible. Here we leverage our expertise in computational antibody engineering to rationally design/optimize three previously reported SARS-CoV neutralizing antibodies and share our proposal towards anti-SARS-CoV-2 biologics therapeutics. SARS-CoV neutralizing antibodies, m396, 80R, and CR-3022 were chosen as templates due to their diversified epitopes and confirmed neutralization potency against SARS. Structures of variable fragment (Fv) in complex with receptor binding domain (RBD) from SARS-CoV or SARS-CoV2 were subjected to our established in silico antibody engineering platform to improve their binding affinity to SARS-CoV2 and developability profiles. The selected top mutations were ensembled into a focused library for each antibody for further screening. In addition, we convert the selected binders with different epitopes into the trispecific format, aiming to increase potency and to prevent mutational escape. Lastly, to avoid antibody induced virus activation or enhancement, we applied NNAS and DQ mutations to the Fc region to eliminate effector functions and extend half-life.
  🖺 Full Text HTML: Application of an integrated computational antibody engineering platform to design SARS-CoV-2 neutralizers
• Neutralization of European, South African, and United States SARS-CoV-2 mutants by a human antibody and antibody domains -
  Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission with several emerging variants remain uncontrolled in many countries, indicating the pandemic remains severe. Recent studies showed reduction of neutralization against these emerging SARS-CoV-2 variants by vaccine-elicited antibodies. Among those emerging SARS-CoV-2 variants, a panel of amino acid mutations was characterized including those in the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. In the present study, we evaluated our previously identified antibody and antibody domains for binding to these RBD variants with the emerging mutations, and neutralization of pseudo typed viruses carrying spike proteins with such mutations. Our results showed that one previously identified antibody domain, ab6, can bind 32 out of 35 RBD mutants tested in an ELISA assay. All three antibodies and antibody domains can neutralize pseudo typed B.1.1.7 (UK variant), but only the antibody domain ab6 can neutralize the pseudo typed virus with the triple mutation (K417N, E484K, N501Y). This domain and its improvements have potential for therapy of infections caused by SARS-CoV-2 mutants.
  🖺 Full Text HTML: Neutralization of European, South African, and United States SARS-CoV-2 mutants by a human antibody and antibody domains
• A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic -

  SARS-CoV-2 genomic surveillance in Uganda provides an opportunity to provide a focused description of the virus evolution in a small landlocked East African country. Here we show a recent shift in the local epidemic with a newly emerging lineage A.23 evolving into A.23.1 which is now dominating the Uganda cases and has spread to 26 other countries. Although the precise changes in A.23.1 as it has adapted are different from the changes in the variants of concern (VOC), the evolution shows convergence on a similar set of proteins. The A.23.1 spike protein coding region has accumulated changes that resemble many of the changes seen in VOC including a change at position 613, a change in the furin cleavage site that extends the basic amino acid motif, and multiple changes in the immunogenic N-terminal domain. In addition, the A.23.1lineage encodes changes in non-spike proteins that other VOC show (nsp6, ORF8 and ORF9). The clinical impact of the A.23.1 variant is not yet clear, however it is essential to continue careful monitoring of this variant, as well as rapid assessment of the consequences of the spike protein changes for vaccine efficacy.

  🖺 Full Text HTML: A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic
• Dry Swab Method of sample collection for SARS-CoV2 testing can be used for culturing virus -
  Background: Earlier studies suggested the use of dry swab method for SARS-CoV-2 detection as it does not need VTM and subsequent RNA extraction step making the process cheaper, safer and faster. In this study we explore whether the virus in the dry swab is viable and can be cultured and propagated. Method: Swabs were spiked with SARS-CoV-2 and stored in three different conditions: a) as dry swab (SD, eluted in 1 mL DMEM), b) in 1 mL of Viral Transport Medium (SVTM), and c) in 1 mL of Tris-EDTA buffer (STE). The sample groups were stored either at room temperature (RT ,25{degrees}C{+/-}1{degrees}C) or at 4{degrees}C for 1, 4, 8, 12, 24, 48 and 72 hours before being used as viral inoculums for the propagation studies in Vero cells. Results: The RT-qPCR data suggests that SD incubated both at RT and 4{degrees}C harbors viral particles that are viable and culturable at par with SVTM and STE. Conclusion: The dry swab method, in addition to its advantages in detection of the virus, also renders viable viral particles that can be cultured and propagated.
  🖺 Full Text HTML: Dry Swab Method of sample collection for SARS-CoV2 testing can be used for culturing virus
• Characterization and functional interrogation of SARS-CoV-2 RNA interactome -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 pandemic, which has caused a devastating global health crisis. The emergence of highly transmissible novel viral strains that escape neutralizing responses emphasizes the urgent need to deepen our understanding of SARS-CoV-2 biology and to develop additional therapeutic strategies. Using a comprehensive identification of RNA binding proteins (RBP) by mass spectrometry (ChIRP-M/S) approach, we identified 142 high-confidence cellular factors that bind the SARS-CoV-2 viral genome during infection. By systematically knocking down their expression in a human lung epithelial cell line, we found that the majority of the RBPs identified in our study are proviral factors that regulate SARS-CoV-2 genome replication. We showed that some of these proteins represented drug targets of interest for inhibiting SARS-CoV-2 infection. In conclusion, this study provides a comprehensive view of the SARS-CoV-2 RNA interactome during infection and highlights candidates for host-centered antiviral therapies.
  🖺 Full Text HTML: Characterization and functional interrogation of SARS-CoV-2 RNA interactome
• The Dual-Antigen Ad5 COVID-19 Vaccine Delivered as an Intranasal Plus Subcutaneous Prime Elicits Th1 Dominant T-Cell and Humoral Responses in CD-1 Mice -
  In response to the need for an efficacious, thermally-stable COVID-19 vaccine that can elicit both humoral and cell-mediated T-cell responses, we have developed a dual-antigen human adenovirus serotype 5 (hAd5) COVID-19 vaccine in formulations suitable for subcutaneous (SC), intranasal (IN), or oral delivery. The vaccine expresses both the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins using an hAd5 platform with E1, E2b, and E3 sequences deleted; hAd5(E1-, E2b-, E3-); that is effective even in the presence of hAd5 immunity. In the vaccine, S is modified (S-Fusion) for enhanced cell surface display to elicit humoral responses and N is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal pathway to increase MHC I and II presentation. Initial studies using subcutaneous (SC) prime and SC boost vaccination of CD-1 mice demonstrated that the hAd5 S-Fusion + N-ETSD vaccine elicits T-helper cell 1 (Th1) dominant T-cell and humoral responses to both S and N. We then compared SC to IN prime vaccination with either an SC or IN boost post-SC prime and an IN boost after IN prime. These studies reveal that IN prime/IN boost is as effective at generating Th1 dominant humoral responses to both S and N as the other combinations, but that the SC prime with either an IN or SC boost elicits greater T cell responses. In a third study to assess the power of the two routes of delivery when used together, we used a combined SC plus IN prime with or without a boost and found the combined prime alone to be as effective as the combined prime with either an SC or IN boost in generating both humoral and T-cell responses. The findings here in CD-1 mice demonstrate that combined SC and IN prime-only delivery has the potential to provide broad immunity, including mucosal immunity, against SARS-CoV-2 and supports further testing of this delivery approach in additional animal models and clinical trials.
  🖺 Full Text HTML: The Dual-Antigen Ad5 COVID-19 Vaccine Delivered as an Intranasal Plus Subcutaneous Prime Elicits Th1 Dominant T-Cell and Humoral Responses in CD-1 Mice
• Protein-primed RNA synthesis in SARS-CoVs and structural basis for inhibition by AT-527 -
  How viruses from the Coronaviridae family initiate viral RNA synthesis is unknown. Here we show that the SARS-CoV-1 and -2 Nidovirus RdRp-Associated Nucleotidyltransferase (NiRAN) domain on nsp12 uridylates the viral cofactor nsp8, forming a UMP-Nsp8 covalent intermediate that subsequently primes RNA synthesis from a poly(A) template; a protein-priming mechanism reminiscent of Picornaviridae enzymes. In parallel, the RdRp active site of nsp12 synthesizes a pppGpU primer, which primes (-)ssRNA synthesis at the precise genome-poly(A) junction. The guanosine analogue 5’-triphosphate AT-9010 (prodrug: AT-527) tightly binds to the NiRAN and inhibits both nsp8-labeling and the initiation of RNA synthesis. A 2.98 A resolution Cryo-EM structure of the SARS-CoV-2 nsp12-nsp7-(nsp8)2 /RNA/NTP quaternary complex shows AT-9010 simultaneously binds to both NiRAN and RdRp active site of nsp12, blocking their respective activities. AT-527 is currently in phase II clinical trials, and is a potent inhibitor of SARS-CoV-1 and -2, representing a promising drug for COVID-19 treatment.
  🖺 Full Text HTML: Protein-primed RNA synthesis in SARS-CoVs and structural basis for inhibition by AT-527
• V367F mutation in SARS-CoV-2 spike RBD emerging during the early transmission phase enhances viral infectivity through increased human ACE2 receptor binding affinity -
  The current global pandemic of COVID-19 is caused by a novel coronavirus SARS-CoV-2. The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring mutations in the RBD have altered the receptor binding affinity and infectivity, firstly we analyzed in silico the binding dynamics between mutated SARS-CoV-2 RBDs and the human ACE2 receptor. Among 1609 genomes of SARS-CoV-2 strains isolated during the early transmission phase, 32 non-synonymous RBD mutants were identified and found clustered into nine mutant types under high positive selection pressure. Applying molecular dynamics simulations, three mutant types (V367F, W436R, N354D/D364Y) displayed higher binding affinity to human ACE2, likely due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The increased infectivity of one mutant (V367F) circulating worldwide was further validated by performing receptor-ligand binding ELISA, surface plasmon resonance, and pseudotyped virus assays. Genome phylogenetic analysis of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F + D614G), which emerged later and formed a distinct sub-cluster. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of SARS-CoV-2 under high selection pressure and supports the continuing surveillance of spike mutations to aid in the development of COVID-19 drugs and vaccines.
  🖺 Full Text HTML: V367F mutation in SARS-CoV-2 spike RBD emerging during the early transmission phase enhances viral infectivity through increased human ACE2 receptor binding affinity
• Emergence of the E484K Mutation in SARS-CoV-2 Lineage B.1.1.220 in Upstate New York -

  Ongoing surveillance detected a SARS-CoV-2 B.1.1.220 variant carrying the E484K substitution in four patients from a hospital network in upstate New York. Patients reported no travel history and shared no obvious epidemiological linkage. A search of online databases identified 12 additional B.1.1.220 with E484K, all of which were detected in New York since December 2020. Detailed genomic analyses suggests that the mutation has emerged independently in at least two different B.1.1.220 strains in this region.

  🖺 Full Text HTML: Emergence of the E484K Mutation in SARS-CoV-2 Lineage B.1.1.220 in Upstate New York
• Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant -

  The variant of concern (VOC) P.1 emerged in the Amazonas state (Brazil) in November-2020. It contains a constellation of mutations, ten of them in the spike protein. Consequences of these specific mutations at the population level have been little studied so far, despite the detection of P.1 variant in 26 countries, with local transmission in at least four other countries in the Americas and Europe. Here, we estimate P.19s transmissibility and reinfection using a model-based approach, by fitting data from the Brazilian national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December 2020 to February 2021, when the city was devastated by four times more cases than in the previous peak (April 2020). The new variant was found to be about 2.6 times more transmissible (95% Confidence Interval (CI): 2.4–2.8) than previous circulating variant(s). The city already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus (estimated as 78%, CI:73–83%), and the fitted model attributed 28% of the cases during the period to reinfections by the variant P.1. Our estimates rank P.1 as the most transmissible among the current identified SARS-CoV-2 VOCs, posing a serious threat and requiring urgent measures to control its global spread.

  🖺 Full Text HTML: Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant
• Antidepressant and antipsychotic drugs reduce viral infection by SARS-CoV-2 and fluoxetine show antiviral activity against the novel variants in vitro -
  Background and Purpose: Repurposing of currently available drugs is a valuable strategy to tackle the consequences of COVID-19. Recently, several studies have investigated the effect of psychoactive drugs on SARS-CoV-2 in cell culture models as well as in clinical practice. Our aim was to expand these studies and test some of these compounds against newly emerged variants. Experimental Approach: Several antidepressant drugs and antipsychotic drugs with different primary mechanisms of action were tested in ACE2/TMPRSS2-expressing human embryonic kidney cells against the infection by SARS-CoV-2 spike protein-dependent pseudoviruses. Some of these compounds were also tested in human lung epithelial cell line, Calu-1, against the first wave (B.1) lineage of SARS-CoV-2 and the variants of concern, B.1.1.7 and B.1.351. Key Results: Several clinically used antidepressants, including fluoxetine, citalopram, reboxetine, imipramine, as well as antipsychotic compounds chlorpromazine, flupenthixol, and pimozide inhibited the infection by pseudotyped viruses with minimal effects on cell viability. The antiviral action of several of these drugs was verified in Calu-1 cells against the (B.1) lineage of SARS-CoV-2. By contrast, the anticonvulsant carbamazepine, and novel antidepressants ketamine and its derivatives as well as MAO and phosphodiesterase inhibitors phenelzine and rolipram, respectively, showed no activity in the pseudovirus model. Furthermore, fluoxetine remained effective against pseudo viruses with N501Y, K417N, and E484K spike mutations, and the VoC-1 (B.1.1.7) and VoC-2 (B.1.351) variants of SARS-CoV-2. Conclusion and Implications: Our study confirms previous data and extends information on the repurposing of these drugs to counteract SARS-CoV-2 infection including different variants of concern.
  🖺 Full Text HTML: Antidepressant and antipsychotic drugs reduce viral infection by SARS-CoV-2 and fluoxetine show antiviral activity against the novel variants in vitro
• The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection -
  We identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone, a compound in clinical trials for anti-fibrotic and anti-inflammatory applications, as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry. We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection. Halofuginone also potently suppresses SARS-CoV-2 replication post-entry. Utilizing analogues of halofuginone and small molecule inhibitors of the PRS, we establish that inhibition of HS presentation and viral replication is dependent on proline tRNA synthesis opposed to PRS activation of the integrated stress response (ISR). Moreover, we provide evidence that these effects are mediated by the depletion of proline tRNAs. In line with this, we find that SARS-CoV-2 polyproteins, as well as several HS proteoglycans, are particularly proline-rich, which may make them vulnerable to halofuginone translational suppression. Halofuginone is orally bioavailable, has been evaluated in a phase I clinical trial in humans and distributes to SARS-CoV-2 target organs, including the lung, making it a promising clinical trial candidate for the treatment of COVID-19.
  🖺 Full Text HTML: The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection

From Clinical Trials

• Pilot Trial of XFBD, a TCM, in Persons With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Xuanfei Baidu Granules;   Other: Placebo
  Sponsor:   Darcy Spicer
  Recruiting

• Safety and Tolerability of Emricasan in Symptomatic Outpatients Diagnosed With Mild-COVID-19 - Condition:   Covid19
  Interventions:   Drug: Emricasan;   Other: Placebo
  Sponsor:   Histogen
  Recruiting

• Efficacy of Reinforcing Standard Therapy in COVID-19 Patients With Repeated Transfusion of Convalescent Plasma - Condition:   Covid19
  Interventions:   Other: Convalescent Plasma with antibody against SARS-CoV-2.;   Other: Standard treatment for COVID-19
  Sponsors:   Hospital Son Llatzer;   Fundació d’investigació Sanitària de les Illes Balears
  Recruiting

• ANTIcoagulation in Severe COVID-19 Patients - Condition:   Severe COVID-19 Pneumonia
  Interventions:   Drug: Tinzaparin, Low dose prophylactic anticoagulation;   Drug: Tinzaparin, High dose prophylactic anticoagulation;   Drug: Tinzaparin,Therapeutic anticoagulation
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Neuromodulation in COVID-19 Patients - Condition:   COVID-19
  Interventions:   Device: Transcranial direct-current stimulation;   Device: Sham Transcranial direct-current stimulation
  Sponsors:   D’Or Institute for Research and Education;   Rio de Janeiro State Research Supporting Foundation (FAPERJ);   Conselho Nacional de Desenvolvimento Científico e Tecnológico;   Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
  Not yet recruiting

• Immunogenicity and Safety of Recombinant COVID-19 Vaccine (CHO Cells) - Condition:   COVID-19
  Interventions:   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (60-85 years) at the schedule of day 0, 28, 56
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   Academy of Military Medical Sciences，Academy of Military Sciences，PLA ZHONGYIANKE Biotech Co, Ltd. LIAONINGMAOKANGYUAN Biotech Co, Ltd
  Recruiting

• Off-the-shelf NK Cells (KDS-1000) as Immunotherapy for COVID-19 - Condition:   Covid19
  Interventions:   Biological: KDS-1000;   Other: Placebo
  Sponsor:   Kiadis Pharma
  Not yet recruiting

• Corticosteroids for COVID-19 - Condition:   Covid19
  Interventions:   Drug: Prednisone;   Device: Point of Care testing device for C-reactive protein
  Sponsor:   University of Alberta
  Not yet recruiting

• Effects of Telerehabilitation After Discharge in COVID-19 Survivors - Condition:   Covid19
  Intervention:   Other: Telerehabilitation
  Sponsor:   Hacettepe University
  Recruiting

• A Study to Assess if a Medicine Called Bamlanivimab is Safe and Effective in Reducing Hospitalization Due to COVID-19 - Condition:   Covid19
  Interventions:   Biological: Bamlanivimab;   Other: Standard of Care
  Sponsors:   Fraser Health;   Fraser Health Authrority Department of Evaluation and Research Services;   Surrey Memorial Hospital Clinical Research Unit;   Centre for Health Evaluation and Outcome Sciences;   Surrey Hospitals Foundation;   BC Support Unit;   University of British Columbia;   Ministry of Health, British Columbia
  Not yet recruiting

• Post COVID-19 Syndrome and the Gut-lung Axis - Condition:   Covid19
  Interventions:   Dietary Supplement: Omni-Biotic Pro Vi 5;   Dietary Supplement: Placebo
  Sponsors:   Medical University of Graz;   CBmed Ges.m.b.H.
  Not yet recruiting

• Efficacy of Adaptogens in Patients With Long COVID-19 - Condition:   Covid19
  Interventions:   Dietary Supplement: ADAPT-232 oral solution;   Other: Placebo oral solution
  Sponsors:   Swedish Herbal Institute AB;   National Family Medicine Training Centre, Georgia;   Tbilisi State Medical University;   Phytomed AB
  Not yet recruiting

• COVID-19 Self-Testing Through Rapid Network Distribution - Condition:   Covid19
  Interventions:   Behavioral: COVID-19 self-test;   Behavioral: COVID-19 test referral
  Sponsors:   University of Pennsylvania;   Public Health Management Corporation
  Not yet recruiting

• Monitoring of COVID-19 Seroprevalence Among GHdC Staff Members - Condition:   Covid19
  Intervention:   Diagnostic Test: Serology to determine SARS-CoV-2 infection
  Sponsor:   Grand Hôpital de Charleroi
  Recruiting

• UNITE Study (UCSD-SW) for COVID-19 - Condition:   Covid19
  Intervention:   Device: Splenic Ultrasound
  Sponsors:   Imanuel Lerman;   SecondWave Systems Inc.;   MCDC (Unites States Department of Defense)
  Recruiting

From PubMed

• Preparedness for self-isolation or quarantine and lockdown in South Africa: results from a rapid online survey - CONCLUSION: The findings highlight the challenge of implementing self-isolation or quarantine in a country with different and unique social contexts. There is a need for public awareness regarding the importance of self-isolation or quarantine as well as counter measures against contextual factors inhibiting this intervention, especially in impoverished communities.

• Famotidine Repurposing for Novel Corona Virus Disease of 2019: A Systematic Review - CONCLUSION: Famotidine has the potential to answer the ongoing global challenge owing to its selective action on viral replication. Additionally, clinical findings in COVID-19 patients support its efficacy to reduce clinical symptoms of COVID-19.We suggest that further optimally powered randomized clinical trials should be carried out to come up with definitive conclusions.

• Could Soluble Endothelial Protein C Receptor Levels Recognize Sars-Cov2-Positive Patients Requiring Hospitalization? - CONCLUSIONS: In our cohort, sEPCR levels in COVID-19 patients upon hospital admission appear considerably elevated compared to outpatients; this could lead to impaired APC activities and might contribute to the pro-coagulant phenotype reported in such patients. sEPCR measurement might be useful as a point-of-care test in SARS-CoV2 positive patients.

• Local Angiotensin-Converting Enzyme 2 Gene Expression in Kidney Allografts Is Not Affected by Renin-Angiotensin-Aldosterone Inhibitors - CONCLUSIONS: ACEis or ARBs in kidney transplant recipients do not affect local ACE2 expression. This observation supports long-term RAAS treatment in kidney transplant recipients, despite acute complications such as COVID-19 where ACE2 serves as the entry protein for infection.

• Early combination treatment with existing HIV antivirals: an effective treatment for COVID-19? - CONCLUSIONS: The combination of a protease inhibitor and two nucleoside analogues, drugs widely used to treat HIV infection, could be evaluated in clinical trials for the treatment of COVID-19.

• Direct Observation of Protonation State Modulation in SARS-CoV-2 Main Protease upon Inhibitor Binding with Neutron Crystallography - The main protease (3CL M^(pro)) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is an essential enzyme for viral replication with no human counterpart, making it an attractive drug target. To date, no small-molecule clinical drugs are available that specifically inhibit SARS-CoV-2 M^(pro). To aid rational drug design, we determined a neutron structure of M^(pro) in complex with the α-ketoamide inhibitor telaprevir at near-physiological (22 °C)…

• 2D MXenes with antiviral and immunomodulatory properties: a pilot study against SARS-CoV-2 - Two-dimensional transition metal carbides/carbonitrides known as MXenes are rapidly growing as multimodal nanoplatforms in biomedicine. Here, taking SARS-CoV-2 as a model, we explored the antiviral properties and immune-profile of a large panel of four highly stable and well-characterized MXenes - Ti(3)C(2)T(x), Ta(4)C(3)T (x) , Mo(2)Ti(2)C(3)T (x) and Nb(4)C(3)T (x) . To start with antiviral assessment, we first selected and deeply analyzed four different SARS-CoV-2 genotypes, common in most…

• Wild Sambucus nigra L. from north-east edge of the species range: A valuable germplasm with inhibitory capacity against SARS-CoV2 S-protein RBD and hACE2 binding in vitro - Berries and flowers of Sambucus nigra L. tree are well known for their ability to mitigate symptoms of upper respiratory disorders related to reported antiviral properties. Industrial application and commercial cultivation of S. nigra is largely limited to a few widely grown cultivars. Restricted genetic diversity of cultivated S. nigra can be disadvantageous if new industrial applications are discovered. In this study wild S. nigra populations located on the north-east edge of the species…

• SARS-CoV-2 main protease inhibition by compounds isolated from Luffa cylindrica using molecular docking - In this study, chemical investigation of methanol extract of the air-dried fruits of Luffa cylindrica led to the identification of a new δ-valerolactone (1), along with sixteen known compounds (2-17). Their chemical structures including the absolute configuration were elucidated by extensive spectroscopic analysis and electronic circular dichroism analysis, as well as by comparison with those reported in the literature. For the first time in literature, we have examined the binding potential of…

• DNA vaccine candidate encoding SARS-CoV-2 spike proteins elicited potent humoral and Th1 cell-mediated immune responses in mice - More than 65 million people have been confirmed infection with SARS-CoV-2 and more than 1 million have died from COVID-19 and this pandemic remains critical worldwide. Effective vaccines are one of the most important strategies to limit the pandemic. Here, we report a construction strategy of DNA vaccine candidates expressing full length wild type SARS-CoV-2 spike (S) protein, S1 or S2 region and their immunogenicity in mice. All DNA vaccine constructs of pCMVkan-S, -S1 and -S2 induced high…

• Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2 - Up to date, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells. In vivo studies indicate that…

• Evaluation of the safety and efficacy of XAV-19 in patients with COVID-19-induced moderate pneumonia: study protocol for a randomized, double-blinded, placebo-controlled phase 2 (2a and 2b) trial - BACKGROUND: Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for…

• A small molecule compound berberine as an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study - The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced…

• Herbal Medicine in Fighting Against COVID-19: New Battle with an Old Weapon - World population has been suffering due to the outbreak of present pandemic situation of COVID-19. The disease has become life-threatening in a very short time with touching on most of the citizenry and economic systems globally. The novel virus, SARS-CoV-2 has been known as the causative agent of COVID-19. The SARS-CoV-2 is single stranded RNA virus having ~30 kb genomic components which are 70% identical to SARS-CoV. The main process of pathophysiology of COVID-19 has been associated with the…

• On the search for COVID-19 therapeutics: identification of potential SARS-CoV-2 main protease inhibitors by virtual screening, pharmacophore modeling and molecular dynamics - COVID-19 also known as SARS-CoV-2 outbreak in late 2019 and its worldwide pandemic spread has taken the world by surprise. The minute-to-minute increasing coronavirus cases (>85 M) and progressive deaths (≈1.8 M) calls for finding a cure to this devastating pandemic. While there have been many attempts to find biologically active molecules targeting SARS-CoV-2 for treatment of this viral infection, none has found a way to the clinic yet. In this study, a 3-feature structure-based pharmacophore…

From Patent Search

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

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

• Sars-CoV-2 vaccine antigens - - link

• SARS-COV-2 BINDING PROTEINS - - link

• Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen -

  Ein Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen, umfassend: ein Bildschirmgerät, das einen Umfang hat; eine UV-Entkeimungslampe, die sich am Umfang des Bildschirmgeräts befindet; eine Stromquelle, die elektrisch mit der UV-Entkeimungslampe verbunden ist; eine Steuerschaltung, die elektrisch mit der UV-Entkeimungslampe verbunden ist; und eine Befestigungsvorrichtung, durch die die UV-Entkeimungslampe am Umfang des Bildschirmgeräts befestigbar ist, wobei die Befestigungsvorrichtung einen Sitzkörper, eine erste Klemmplatte und eine zweite Klemmplatte aufweist, wobei der Sitzkörper mit der UV-Entkeimungslampe versehen ist, wobei die erste Klemmplatte und die zweite Klemmplatte beabstandet am Sitzkörper gleitbar angeordnet sind, wodurch ein Klemmabstand zwischen der ersten Klemmplatte und der zweiten Klemmplatte besteht, wobei ein elastisches Element zwischen der zweiten Klemmplatte und dem Sitzkörper angeordnet ist, um die zweite Klemmplatte dazu zu zwingen, sich der ersten Klemmplatte zu nähern.

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• Schublade mit antiepidemischer Wirkung -

  Schublade mit antiepidemischer Wirkung, mit einem Schrank (1); mindestens einer Schublade (2), die in dem Schrank (1) angeordnet ist, wobei jede Schublade (2) einen Schubladenraum (25) aufweist; einer UV-Sterilisationsvorrichtung (3), die an der Schublade (2) angeordnet ist; einer Stromquelle (4), die elektrisch mit der UV-Sterilisationsvorrichtung (3) verbunden ist; einer Steuerschaltung (5), die elektrisch mit der Stromquelle (4) und der UV-Sterilisationsvorrichtung (3) verbunden ist; und einem Sensor (6), der elektrisch mit der Steuerschaltung (5) verbunden ist.

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• Gerät zur Unterstützung und Verstärkung natürlicher Lüftung -

  Lüftungssystem für einen mit öffnbaren Fenstern (16) ausgestatteten Gebäuderaum, gekennzeichnet dadurch, dass es ein Gehäuse (18) und einen Ventilator (20) aufweist, wobei durch das Gehäuse eine vom Ventilator erzeugte Luftströmung strömen kann, wobei das Gehäuse dafür eine Einströmöffnung (24) für Luft und eine Ausströmöffnung (22) für Luft enthält, wobei eine der beiden Öffnungen der Form eines Öffnungsspalts (26) zwischen einem Fensterflügel (12) und einem Blendrahmen (14) des Fensters (16) angepasst ist.

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• X射线图像识别方法、装置、计算机设备及存储介质 - 本申请涉及一种X射线图像识别方法、装置、计算机设备和存储介质。通过获取X射线图像，将X射线图像作为训练样本；构建多注意力交互网络，多注意力交互网络包括卷积批处理标准化网络、特征提取网络和输出网络；其中特征提取网络包括多注意力交互特征提取模块和批标准化模块，特征提取网络通过学习通道之间的相关性，多通道之间的信息交互来达到增强模型的识别能力。利用训练样本对多注意力交互网络进行训练，得到X射线图像识别模型；获取待测X射线图像；将待测X射线图像输入到X射线图像识别模型中，得到X射线图像的类别。本方法减少了网络的参数量和计算量，提高了模型的泛化能力。 - link

• 利用HEK293细胞制备新型冠状病毒核衣壳蛋白的方法 - 本发明提供一种利用HEK293细胞制备新型冠状病毒核衣壳蛋白的方法，包括：1）构建新冠病毒核衣壳蛋白（N蛋白）重组表达载体；2）用重组表达载体转染HEK293细胞；3）体外培养细胞，从培养上清中分离纯化N蛋白。利用HEK293表达系统可在短时间内获得大量新冠病毒N蛋白，通过一步亲和层析法可获得纯度高达98%以上的N蛋白。与大肠杆菌相比，采用HEK293表达系统制备的N蛋白在与抗体的结合活性及新冠抗体胶体金检测方面均表现出极大优势，且HEK293表达系统制备的N蛋白其蛋白空间构象接近于病毒N基因在宿主体内的蛋白表达构象，具有更高的免疫诊断和抗体制备的准确性，将其用于制作诊断试剂和疫苗前景广阔。 - link

• Compositions and methods for detecting SARS-CoV-2 spike protein - - link