Covid-19 Sentry

Contents

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

From Preprints

• How many relevant SARS-CoV-2 variants might we expect in the future? -

  Objectives: The emergence of new SARS-CoV-2 variants is a major challenge in the management of Covid-19 pandemic. A crucial issue is to quantify the number of variants which may represent a potential risk for public health in the future. Methods: We fitted the data on the most relevant SARS-CoV-2 variants recorded by the World Health Organization (WHO). The function exploited for the fit is related to the total number of infected subjects in the world since the start of the epidemic. Results: We found that the number of relevant SARS-CoV-2 variants up to November 2021 was about 44. Moreover, the number of new relevant variants per ten million cases turned out to be 1.64 in November 2021, slightly decreased in comparison to the value of 2.29 in March 2020. Conclusions: Our simple mathematical model can evaluate the number of relevant SARS-CoV-2 variants as the cumulative number of cases increase worldwide and may represent a useful tool in planning strategies to effectively contrast the pandemic.

  🖺 Full Text HTML: How many relevant SARS-CoV-2 variants might we expect in the future?
• Requirements for the containment of COVID-19 disease outbreaks through periodic testing, isolation, and quarantine -

  We employ individual-based Monte Carlo computer simulations of a stochastic SEIR model variant on a two- dimensional Newman-Watts small-world network to investigate the control of epidemic outbreaks through periodic testing and isolation of infectious individuals, and subsequent quarantine of their immediate contacts. Using disease parameters informed by the COVID-19 pandemic, we investigate the effects of various crucial mitigation features on the epidemic spreading: fraction of the infectious population that is identifiable through the tests; testing frequency; time delay between testing and isolation of positively tested individuals; and the further time delay until quarantining their contacts as well as the quarantine duration. We thus determine the required ranges for these intervention parameters to yield effective control of the disease through both considerable delaying the epidemic peak and massively reducing the total number of sustained infections.

  🖺 Full Text HTML: Requirements for the containment of COVID-19 disease outbreaks through periodic testing, isolation, and quarantine
• Bringing Home Baby Euclid: Testing Infants’ Basic Shape Discrimination Online -
  Online developmental psychology studies are still in their infancy, but their role is newly urgent in the light of the COVID-19 pandemic and the suspension of in-person research. Are online studies with infants a suitable stand-in for lab-based studies? Across two unmonitored online experiments using a change-detection looking-time paradigm with 96 7-month-old infants, we found that infants did not exhibit measurable sensitivities to the basic shape information that distinguishes between 2D geometric forms, as had been observed in previous lab experiments. Moreover, while infants were distracted in our online experiments, such distraction was nevertheless not a reliable predictor of their ability to discriminate shape information. Our findings suggest that the change-detection paradigm may not elicit infants’ shape discrimination abilities when stimuli are presented on small, personal computer screens because infants may not perceive two discrete events with only one event displaying uniquely changing information that draws their attention. Some developmental paradigms used with infants, even those that seem well-suited to the constraints and goals of online data collection, may thus not yield results consistent with lab results that rely on highly controlled settings and specialized equipment, such as large screens. As developmental researchers continue to adapt lab-based methods to online contexts, testing those methods online is a necessary first step in creating robust tools and expanding the space of inquiry for developmental science conducted online.
  🖺 Full Text HTML: Bringing Home Baby Euclid: Testing Infants’ Basic Shape Discrimination Online
• Rapid expansion of SARS-CoV-2 variants of concern is a result of adaptive epistasis -
  The SARS-CoV-2 pandemic recently entered an alarming new phase with the emergence of the variants of concern (VOC) and understanding their biology is paramount to predicting future ones. Current efforts mainly focus on mutations in the spike glycoprotein (S), but changes in other regions of the viral proteome are likely key. We analyzed more than 900,000 SARS-CoV-2 genomes with a computational systems biology approach including a haplotype network and protein structural analyses to reveal lineage-defining mutations and their critical functional attributes. Our results indicate that increased transmission is promoted by epistasis, i.e., combinations of mutations in S and other viral proteins. Mutations in the non-S proteins involve immune-antagonism and replication performance, suggesting convergent evolution. Furthermore, adaptive mutations appear in geographically disparate locations, suggesting that either independent, repeat mutation events or recombination among different strains are generating VOC. We demonstrate that recombination is a stronger hypothesis, and may be accelerating the emergence of VOC by bringing together cooperative mutations. This emphasizes the importance of a global response to stop the COVID-19 pandemic.
  🖺 Full Text HTML: Rapid expansion of SARS-CoV-2 variants of concern is a result of adaptive epistasis
• High viral loads: what drives fatal cases of COVID-19 in vaccinees? an autopsy study -

  Background: The rate of SARS-CoV-2 breakthrough infections in vaccinees is becoming an increasingly serious issue. Objective: To determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types. Design: Comprehensive retrospective observational cohort study. Setting: Consecutive cases from four German academic medical centers. Patients: Deceased with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Collections of 29 vaccinees which were analyzed and compared to 141 nonvaccinated control cases. Results: Autopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT- PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within the organism in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008). Vaccinated cases also showed high viral loads, reaching Ct values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. A fatal course after vaccination occurred in only 14% of all COVID-19 deceased in Augsburg. Limitations: Restricted number of cases Conclusions: Fatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions. Interestingly, we observed striking virus dissemination in our case study, which may indicate a decreased ability to eliminate the virus in patients with an impaired immune system. However, the potential role of antibody- dependent enhancement must also be ruled out in future studies.

  🖺 Full Text HTML: High viral loads: what drives fatal cases of COVID-19 in vaccinees? an autopsy study
• SARS-CoV-2 incidence, transmission and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-2021 -

  Background By August 2021, South Africa experienced three SARS-CoV-2 waves; the second and third associated with emergence of Beta and Delta variants respectively. Methods We conducted a prospective cohort study during July 2020-August 2021 in one rural and one urban community. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Serum was collected every two months and tested for anti-SARS-CoV-2 antibodies. Results Among 115,759 nasal specimens from 1,200 members (follow-up rate 93%), 1976 (2%) were SARS-CoV-2-positive. By rRT-PCR and serology combined, 62% (749/1200) of individuals experienced ≥1 SARS-CoV-2 infection episode, and 12% (87/749) experienced reinfection. Of 662 PCR-confirmed episodes with available data, 15% (n=97) were associated with ≥1 symptom. Among 222 households, 200 (90%) had ≥1 SARS-CoV-2-positive individual. Household cumulative infection risk (HCIR) was 25% (213/856). On multivariable analysis, accounting for age and sex, index case lower cycle threshold value (OR 3.9, 95%CI 1.7-8.8), urban community (OR 2.0,95%CI 1.1-3.9), Beta (OR 4.2, 95%CI 1.7-10.1) and Delta (OR 14.6, 95%CI 5.7-37.5) variant infection were associated with increased HCIR. HCIR was similar for symptomatic (21/110, 19%) and asymptomatic (195/775, 25%) index cases (p=0.165). Attack rates were highest in individuals aged 13-18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 infection. People living with HIV who were not virally supressed were more likely to develop symptomatic illness, and shed SARS- CoV-2 for longer compared to HIV-uninfected individuals. Conclusions In this study, 85% of SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of Beta and Delta variants, likely contributed to successive waves, with >60% of individuals infected by the end of follow-up.

  🖺 Full Text HTML: SARS- CoV-2 incidence, transmission and reinfection in a rural and an urban setting: results of the PHIRST-C cohort study, South Africa, 2020-2021
• The effect of the Pandemic on European Narratives on Smart Cities and Surveillance -
  This paper presents the analysis of European smart city narratives and how they evolved under the pressure of the COVID-19 pandemic. We approach the smart city concept from the critical perspective of surveillance capitalism, as proposed by Zuboff, to highlight the growing privacy concerns related to technological development. We have collected and analysed 184 articles regarding smart city solutions, published on social media by five European journals between 2017 and 2021. We adopted both human and machine coding processes for qualitative and quantitative analysis of our data. As a result, we identified the main actors and four dominant narratives: regulation of AI and facial recognition, technological fight with the climate emergency, contact tracing apps, and the potential of 5G technology to boost the digitalisation processes. Our analysis shows the growing number of positive narratives underlining the importance of technology in fighting the pandemic and mitigating the climate emergency. Although the discourse on surveillance is often accompanied by the consideration of the right to privacy, those types of concerns are central for only two topics out of the four we discovered. We found that the main rationale for the development of surveillance technologies relates to the competitiveness of the EU in the global technological rivalry, rather than increasing societal wellbeing or safeguarding the transparency of new policies.
  🖺 Full Text HTML: The effect of the Pandemic on European Narratives on Smart Cities and Surveillance
• SARS-CoV-2 wildlife surveillance in Ontario and Quebec, Canada -
  Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, is capable of infecting a variety of wildlife species. Wildlife living in close contact with humans are at an increased risk of SARS-CoV-2 exposure and if infected have the potential to become a reservoir for the pathogen, making control and management more difficult. Objective: To conduct SARS-CoV-2 surveillance in urban wildlife from Ontario and Quebec, Canada, increasing our knowledge of the epidemiology of the virus and our chances of detecting spillover from humans into wildlife. Methods: Using a One Health approach, we leveraged activities of existing research, surveillance, and rehabilitation programs among multiple agencies to collect samples from 776 animals from 17 different wildlife species between June 2020 and May 2021. Samples from all animals were tested for the presence of SARS-CoV-2 viral RNA, and a subset of samples from 219 animals across 3 species (raccoons, Procyon lotor; striped skunks, Mephitis mephitis; and mink, Neovison vison) were also tested for the presence of neutralizing antibodies. Results: No evidence of SARS- CoV-2 viral RNA or neutralizing antibodies was detected in any of the tested samples. Conclusion: Although we were unable to identify positive SARS-CoV-2 cases in wildlife, continued research and surveillance activities are critical to better understand the rapidly changing landscape of susceptible animal species. Collaboration between academic, public and animal health sectors should include experts from relevant fields to build coordinated surveillance and response capacity.
  🖺 Full Text HTML: SARS-CoV-2 wildlife surveillance in Ontario and Quebec, Canada
• Drug repurposing screening identified tropifexor as a SARS-CoV-2 papain-like protease inhibitor -
  The global COVID-19 pandemic underscores the dire need of effective antivirals. Encouraging progress has been made in developing small molecule inhibitors targeting the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). However, the development of papain-like protease (PLpro) inhibitors faces several obstacles. Nevertheless, PLpro represents a high-profile drug target given its multifaceted roles in viral replication. PLpro is involved in not only the cleavage of viral polyprotein but also modulation of host immune response. In this study, we conducted a drug- repurposing screening of PLpro against the MedChemExpress bioactive compound library and identified three hits, EACC, KY-226, and tropifexor, as potent PLpro inhibitors with IC50 values ranging from 3.39 to 8.28 micromolar. The three hits showed dose-dependent binding to PLpro in the thermal shift assay. In addition, tropifexor inhibited the cellular PLpro activity in the FlipGFP assay with an IC50 of 10.6 micromolar. Gratifyingly, tropifexor showed antiviral activity against SARS-CoV-2 in Calu-3 cells with an EC50 of 4.03 micromolar, a 7.8-fold increase compared to GRL0617 (EC50 = 31.4 micromolar). Overall, tropifexor represents a novel PLpro inhibitor that can be further developed as SARS-CoV-2 antivirals.
  🖺 Full Text HTML: Drug repurposing screening identified tropifexor as a SARS-CoV-2 papain-like protease inhibitor
• Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection -
  Coronavirus disease 2019 is a respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence on the pathogenesis of SARS-CoV-2 is accumulating rapidly. In addition to structural proteins such as Spike and Envelope, the functional roles of non-structural and accessory proteins in regulating viral life cycle and host immune responses remain to be understood. Here, we show that open reading frame 8 (ORF8) acts as messenger for inter-cellular communication between alveolar epithelial cells and macrophages during SARS- CoV-2 infection. Mechanistically, ORF8 is a secretory protein that can be secreted by infected epithelial cells via both conventional and unconventional secretory pathways. The unconventionally secreted ORF8 recognizes the IL17RA receptor of macrophages and induces cytokine release. However, conventionally secreted ORF8 cannot bind to IL17RA due to N-linked glycosylation. Furthermore, we found that Yip1 interacting factor homolog B (YIF1B) is a channel protein that translocates unglycosylated ORF8 into vesicles for unconventional secretion. Blocking the unconventional secretion of ORF8 via a YIF1B knockout in hACE2 mice attenuates inflammation and yields delayed mortality following SARS-CoV-2 challenge.
  🖺 Full Text HTML: Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection
• Secreted ORF8 is a pathogenic cause of severe Covid-19 and potentially targetable with select NLRP3 inhibitors -
  Despite extensive research, the specific factor associated with SARS-CoV-2 infection that mediates the life- threatening inflammatory cytokine response in patients with severe Covid-19 remains unidentified. Herein we demonstrate that the virus-encoded Open Reading Frame 8 (ORF8) protein is abundantly secreted as a glycoprotein in vitro and in patients with newly diagnosed Covid-19. ORF8 specifically binds to the NOD-like receptor family pyrin domain-containing 3 (NLRP3) in CD14+/CD16+ monocytes to induce an inflammasomal cytokine response. The levels of ORF8 protein in the blood correlate with disease mortality in patients with acute infection, and the disease trajectory in patients with severe Covid-19. Furthermore, in vitro the ORF8-induced inflammasome response can be readily inhibited by the select NLRP3 inhibitor MCC950. Our results identify the pathogenic cause and mechanism of severe disease, and a potential new treatment of severe Covid-19.
  🖺 Full Text HTML: Secreted ORF8 is a pathogenic cause of severe Covid-19 and potentially targetable with select NLRP3 inhibitors
• Systems immune profiling of variant-specific vaccination against SARS-CoV-2 -
  Lipid-nanoparticle(LNP)-mRNA vaccines offer protection against COVID-19. However, multiple variant lineages caused widespread breakthrough infections. There is no report on variant-specific vaccines to date. Here, we generated LNP- mRNAs specifically encoding wildtype, B.1.351 and B.1.617 SARS-CoV-2 spikes, and systematically studied their immune responses in animal models. All three LNP-mRNAs induced potent antibody responses in mice. However, WT-LNP-mRNA vaccination showed reduced neutralization against B.1.351 and B.1.617; and B.1.617-specific vaccination showed differential neutralization. All three vaccine candidates elicited antigen-specific CD8 and CD4 T cell responses. Single cell transcriptomics of B.1.351-LNP-mRNA and B.1.617-LNP-mRNA vaccinated animals revealed a systematic landscape of immune cell populations and global gene expression. Variant-specific vaccination induced a systemic increase in reactive CD8 T cell population, with a strong signature of transcriptional and translational machineries in lymphocytes. BCR-seq and TCR-seq unveiled repertoire diversity and clonal expansions in vaccinated animals. These data provide direct systems immune profiling of variant-specific LNP-mRNA vaccination in vivo.
  🖺 Full Text HTML: Systems immune profiling of variant-specific vaccination against SARS-CoV-2
• Internal Tremors and Vibration Symptoms Among People with Post-Acute Sequelae of SARS-CoV-2: A narrative review of patient reports -

  To introduce the perspective of patients who have PASC with vibrations and tremors as a prominent component, we leveraged the efforts by Survivor Corps, a grassroots COVID-19 patient advocacy group, to gather information from people in their Facebook group suffering from vibrations and tremors. Survivor Corps collected 140 emails and 450 Facebook comments from members. From the emails, we identified 22 themes and 7 broader domains based on common coding techniques for qualitative data and the constant comparative method of qualitative data analysis. Facebook comments were analyzed using Word Clouds to visualize frequency of terms. The respondent emails reflected 7 domains that formed the basis of characterizing their experience with vibrations and tremors. These domains were: (1) symptom experience, description, and anatomic location; (2) initial symptom onset; (3) symptom timing; (4) symptom triggers or alleviators; (5) change from baseline health status; (6) experience with medical establishment; and (7) impact on lives and livelihood. There were 22 themes total, each corresponding to one of the broader domains. The Facebook comments Word Cloud revealed that the 10 most common words used in comments were: tremors (64), covid (55), pain (51), vibrations (43), months (36), burning (29), feet (24), hands (22), legs (21), back (20). Overall, these patient narratives described intense suffering, and there is still no diagnosis or treatment available.

  🖺 Full Text HTML: Internal Tremors and Vibration Symptoms Among People with Post-Acute Sequelae of SARS-CoV-2: A narrative review of patient reports
• A population framework for predicting the proportion of people infected by the far-field airborne transmission of SARS-CoV-2 indoors -

  The number of occupants in a space influences the risk of far-field airborne transmission of the SARS-CoV-2 virus because the likelihood of having infectious and susceptible people both scale with the number of occupants. Mass- balance and dose-response models determine far-field transmission risks for an individual person and a population of people after sub-dividing a large reference space into 10 identical comparator spaces. For a single infected person when the per capita ventilation rate is preserved, the dose received by an individual person in the comparator space is 10-times higher because the equivalent ventilation rate per infected person is lower. However, accounting for population dispersion, such as the community infection rate, the probability of an infected person being present and uncertainty in their viral load, shows the probability of transmission increases with occupancy. Also, far-field transmission is likely to be a rare event that requires a set of Goldilocks conditions that are just right, when mitigation measures have limited effect. Therefore, resilient buildings should deliver the equivalent ventilation rate required by standards and increase the space volume per person, but also require reductions in the viral loads and the infection rate of the wider population.

  🖺 Full Text HTML: A population framework for predicting the proportion of people infected by the far-field airborne transmission of SARS-CoV-2 indoors
• A public antibody class recognizes a novel S2 epitope exposed on open conformations of SARS-CoV-2 spike -
  Delineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigated the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We found that ~82% of SARS-CoV-2 S-reactive B cells show a naive phenotype, which represents an unusually high fraction of total human naive B cells (~0.1%). Approximately 10% of these naive S-reactive B cells shared an IGHV1-69/IGKV3-11 B cell receptor pairing, an enrichment of 18-fold compared to the complete naive repertoire. A proportion of memory B cells, comprising switched (~0.05%) and unswitched B cells (~0.04%), was also reactive with S and some of these cells were reactive with ADAMTS13, which is associated with thrombotic thrombocytopenia. Following SARS-CoV-2 infection, we report an average 37-fold enrichment of IGHV1-69/IGKV3-11 B cell receptor pairing in the S-reactive memory B cells compared to the unselected memory repertoire. This class of B cells targets a previously undefined non-neutralizing epitope on the S2 subunit that becomes exposed on S proteins used in approved vaccines when they transition away from the native pre- fusion state because of instability. These findings can help guide the improvement of SARS-CoV-2 vaccines.
  🖺 Full Text HTML: A public antibody class recognizes a novel S2 epitope exposed on open conformations of SARS-CoV-2 spike

From Clinical Trials

• GlowTest COVID-19 Antigen Home Test Kit QRI Use Study - Condition:   Covid 19
  Intervention:   Diagnostic Test: GlowTest COVID-19 Antigen Home Test
  Sponsors:   Arion Bio;   CSSi Life Sciences
  Not yet recruiting

• Allogenic UCMSCs as Adjuvant Therapy for Severe COVID-19 Patients - Condition:   Covid 19
  Interventions:   Biological: Normoxic Allogenic UCMSC;   Other: Normal saline solution
  Sponsors:   Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia;   Dr. Moewardi General Hospital, Surakarta, Indonesia;   Dr. Sardjito General Hospital, Yogyakarta, Indonesia;   Dr. Hasan Sadikin General Hospital, Bandung, Indonesia;   PT Bifarma Adiluhung
  Recruiting

• Physical Fitness in Young Healthy Adults After COVID-19 Infection - Condition:   COVID-19
  Interventions:   Other: Physical Activity Level;   Other: Evaluation of knee extension and elbow flexion muscle strength;   Other: Evaluation of functional strength of trunk muscles;   Other: Muscle Endurance;   Other: Flexibility;   Other: Balance;   Other: Fatigue
  Sponsor:  
  Baskent University
  Enrolling by invitation

• Using MOST to Optimize an Intervention to Increase COVID-19 Testing for Frontline Essential Workers - Conditions:   COVID-19;   COVID-19 Testing
  Interventions:   Behavioral: Motivational interviewing

1001. counseling;   Behavioral: Text messages (TMs) and quiz questions (QQs);   Behavioral: Peer education;   Behavioral: Access to COVID testing
      Sponsor:   New York University
      Not yet recruiting

• Efficacy of Different COVID-19 Vaccine Combinations in Inducing Long-term Humoral Immunity [PRIBIVAC] - Condition:   COVID-19
  Interventions:   Biological: Homologous mRNA booster vaccine;   Biological: Heterologous mRNA booster vaccine;   Biological: Non-mRNA booster vaccine A;   Biological: Non- mRNA booster vaccine B;   Biological: Non-mRNA booster vaccine C
  Sponsors:   Tan Tock Seng Hospital;   A*Star;   Duke-NUS Graduate Medical School;   KK Women’s and Children’s Hospital
  Recruiting

• Inhaled Recombinant Non-immunogenic Staphylokinase vs Placebo in Patients With COVID-19 - FORRIF Trial - Condition:   COVID-19
  Interventions:   Drug: Recombinant nonimmunogenic staphylokinase;   Drug: Placebo
  Sponsors:   Supergene, LLC;   Russian Academy of Medical Sciences
  Not yet recruiting

• Safety and Immunogenicity of COVID-19 Vaccine, Inactivated in Healthy Population Aged From 3 to 11 Years - Condition:   COVID-19
  Intervention:   Biological: COVID-19 Vaccine,Inactivated
  Sponsor:   Sinovac Biotech Co., Ltd
  Not yet recruiting

• Nutritional Supplementation of Vitamin D, Quercetin and Curcumin With Standard of Care for Managing Mild Early Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Standard of care;   Dietary Supplement: Investigational treatment
  Sponsor:   King Edward Medical University
  Recruiting

• Study to Evaluate the Safety and Efficacy of a Monoclonal Antibody Cocktail for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ADM03820;   Other: Placebo
  Sponsors:  
  Ology Bioservices;   Enabling Biotechnologies (EB)
  Not yet recruiting

• Usefulness of DORNASE in COVID-19 on HFNO - Condition:   COVID-19 Pneumonia
  Intervention:   Procedure: inhalations
  Sponsor:  
  University Medical Centre Ljubljana
  Not yet recruiting

• COVID-19 VACCINE SAFETY AND EFFECTIVENESS - Condition:   SARS-CoV-2 Infection
  Intervention:   Biological: ChAdOx1 nCoV-19 vaccine (AZD1222)
  Sponsors:   Federal University of Espirito Santo;   Instituto René Rachou/Fiocruz
  Recruiting

• The Immune Response of Heterologous Boost Third Dose of mRNA and Protein COVID-19 Vaccine: a Single-blind, and Randomized Study - Conditions:   COVID-19;   Breakthrough Infection
  Interventions:   Biological: BNT162b2;   Biological: mRNA-1273;   Biological: MCV COVID-19 vaccine
  Sponsors:   Chang Gung Memorial Hospital;   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Study of Immunogenicity Equivalence of a Homologous Third Dose of Covid-19 (Recombinante) Vaccine - Condition:   COVID-19
  Intervention:   Biological: Covid -19 (recombinante) vaccine
  Sponsor:   The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
  Recruiting

• Safety and Immunogenicity of Recombinant Protein RBD Fusion Dimer Vaccine Against the Virus That Cause COVID-19, Known as Severe Acute Respiratoy Syndrome Coronavirus 2 (SARS-CoV-2) - Conditions:   COVID-19;   SARS-CoV-2 Acute Respiratory Disease
  Interventions:  
  Biological: COVID-19 Vaccine HIPRA;   Biological: Cominarty (Pfizer-BioNtech)
  Sponsors:  
  Hipra Scientific, S.L.U;   Laboratorios Hipra, S.A.;   National Institute of Hygiene and Epidemiology, Vietnam
  Recruiting

• Proning Early in Awake COVID-19 Hypoxic Respiratory Failure (PREACHR) Study - Conditions:   Covid19;   Respiratory Failure
  Interventions:   Behavioral: Proning;   Other: Supportive Care
  Sponsor:   New York Hospital Queens
  Completed

From PubMed

• The NSP14/NSP10 RNA repair complex as a Pan-coronavirus therapeutic target - The risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a novel assay and in silico modeling and screening, we identified NSP14-NSP10 inhibitors that increase remdesivir’s potency. A model compound, sofalcone,…

• Viral proteases: Structure, mechanism and inhibition - Viral proteases are diverse in structure, oligomeric state, catalytic mechanism, and substrate specificity. This chapter focuses on proteases from viruses that are relevant to human health: human immunodeficiency virus subtype 1 (HIV-1), hepatitis C (HCV), human T-cell leukemia virus type 1 (HTLV-1), flaviviruses, enteroviruses, and coronaviruses. The proteases of HIV-1 and HCV have been successfully targeted for therapeutics, with picomolar FDA-approved drugs currently used in the clinic. The…

• Efficacy and potential mechanisms of Chinese herbal compounds in coronavirus disease 2019: advances of laboratory and clinical studies - The Coronavirus disease 2019 (COVID-19) pandemic is still spread and has made a severe public health threat around the world. To improve disease progression, emerging Chinese herbal compounds were used in clinical practice and some agents have proven beneficial in treating COVID-19. Here, the relevant literature from basic researches to clinical application were identified and comprehensively assessed. A variety of Chinese herbal compounds have been reported to be effective in improving symptoms…

• Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS- CoV-2 Spike Binding to ACE2 - BACKGROUND: Antibodies raised against human seasonal coronaviruses (sCoVs), which are responsible for the common cold, are known to cross-react with SARS-CoV-2 antigens. This prompts questions about their protective role against SARS-CoV-2 infections and COVID-19 severity. However, the relationship between sCoVs exposure and SARS-CoV-2 correlates of protection are not clearly identified.

• Discovery of Di- and Trihaloacetamides as Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity - The main protease (M^(pro)) is a validated antiviral drug target of SARS-CoV-2. A number of M^(pro) inhibitors have now advanced to animal model study and human clinical trials. However, one issue yet to be addressed is the target selectivity over host proteases such as cathepsin L. In this study we describe the rational design of covalent SARS- CoV-2 M^(pro) inhibitors with novel cysteine reactive warheads including dichloroacetamide, dibromoacetamide, tribromoacetamide,…

• A phase I, first-in-human, randomized dose-escalation study of anti-activated factor XII monoclonal antibody garadacimab - Factor XII (FXII) is the principal initiator of the plasma contact system and has proinflammatory and prothrombotic activities. This single-center, first-in-human phase I study aimed to assess the safety and tolerability of single escalating doses of garadacimab, a monoclonal antibody that specifically inhibits activated FXII (FXIIa), in healthy male volunteers. Volunteers were randomized to eight cohorts, with intravenous (i.v.) doses of 0.1, 0.3, 1, 3, and 10 mg/kg and subcutaneous (s.c.)…

• Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 Spike Protein Subunit 1 - A hallmark of COVID-19 is a hyperinflammatory state associated with severity. Monocytes undergo metabolic reprogramming and produce inflammatory cytokines when stimulated with SARS-CoV-2. We hypothesized that binding by the viral spike protein mediates this effect, and that drugs which regulate immunometabolism could inhibit the inflammatory response. Monocytes stimulated with recombinant SARS-CoV-2 spike protein subunit 1 showed a dose-dependent increase in glycolytic metabolism associated with…

• Nucleic Acid-Based Treatments Against COVID-19: Potential Efficacy of Aptamers and siRNAs - Despite significant efforts, there are currently no approved treatments for COVID-19. However, biotechnological approaches appear to be promising in the treatment of the disease. Accordingly, nucleic acid-based treatments including aptamers and siRNAs are candidates that might be effective in COVID-19 treatment. Aptamers can hamper entry and replication stages of the SARS-CoV-2 infection, while siRNAs can cleave the viral genomic and subgenomic RNAs to inhibit the viral life cycle and reduce…

• Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS- CoV-2 - Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus causing serious infectious disease with a high case-fatality of up to 50% in severe cases. Currently, no effective drug has been approved for the treatment of SFTSV infection. Here, we performed a high-throughput screening of a natural extracts library for compounds with activities against SFTSV infection. Three hit compounds, notoginsenoside Ft1, punicalin, and toosendanin were identified for displaying…

• Berry derived constituents in suppressing viral infection: Potential avenues for viral pandemic management - Berries are acknowledged as a rich source of major dietary antioxidants and the fact that berry phenolics exhibit antioxidant property is widely accepted. Berries are abundant in Vitamin C and polyphenols such as anthocyanins, flavonoids, and phenolic acids. Polyphenols are found to have several therapeutic effects such as anti-inflammatory, antioxidant, and antimicrobial properties. Increasing studies are focusing on natural products and their components for alternative therapeutics against…

• Differential Interactions between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. It is known that the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with the human angiotensin-converting enzyme 2 (ACE2) receptor, initiating the entry of SARS-CoV-2. Since its emergence, a number of SARS-CoV-2 variants have been reported, and the variants that show high infectivity are classified as variants of concern…

• Direct and Catalytic C-Glycosylation of Arenes: Expeditious Synthesis of the Remdesivir Nucleoside - Since early 2020, scientists have strived to find an effective solution to fight SARS-CoV-2, especially by developing reliable vaccines that inhibit the spread of the disease and repurposing drugs for combatting its effects on the human body. The antiviral prodrug Remdesivir is still the most widely used therapeutic during the early stage of the infection. However, the current synthetic routes rely on the use of protecting groups, air-sensitive reagents, and cryogenic conditions, impeding the…

• Spherical Neutralizing Aptamer Inhibits SARS-CoV-2 Infection and Suppresses Mutational Escape - New neutralizing agents against SARS-CoV-2 and associated mutant strains are urgently needed for the treatment and prophylaxis of COVID-19. Herein, we develop a spherical cocktail neutralizing aptamer-gold nanoparticle (SNAP) to block the interaction between the receptor-binding domain (RBD) of SARS-CoV-2 and host ACE2. With the multivalent aptamer assembly as well as the steric hindrance effect of the gold scaffold, SNAP exhibits exceptional binding affinity against the RBD with a dissociation…

• DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), known to be more common in the elderly, who also show more severe symptoms and are at higher risk of hospitalization and death. Here, we show that the expression of the angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, increases during aging in mouse and human lungs. ACE2 expression increases upon telomere shortening or dysfunction in both cultured mammalian cells…

• In silico screening of natural compounds to inhibit interaction of human ACE2 receptor and spike protein of SARS- CoV-2 for the prevention of COVID-19 - A computational investigation was carried out to find out potential phytochemicals that could inhibit the binding of human angiotensin-converting enzyme-2 (ACE2) receptors to spike protein of SARS-CoV-2 which is an essential step to gain entry inside human cells and onset of viral infection known as Coronavirus disease (COVID-19). A library of phytochemicals was screened by virtual screening against ACE2 receptors resulting in twenty phytochemicals out of 686 which had binding energy (-11.8 to…

From Patent Search