Covid-19 Sentry

Contents

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

From Preprints

• SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional NSP14 enzyme, possessing exonuclease and mRNA capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscores the dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.
  🖺 Full Text HTML: SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants
• Plasma of COVID-19 patients does not alter electrical resistance of human endothelial blood-brain barrier in vitro. -
  The pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) instigated the most serious global health crisis. Clinical presentation of COVID-19 frequently includes severe neurological and neuropsychiatric symptoms. However, it is presently unknown whether and to which extent pathological impairment of blood-brain barrier (BBB) contributes to the development of neuropathology during COVID-19 progression. In the present study we used human induced pluripotent stem cells-derived brain endothelial cells (iBECs) to study the effects of blood plasma derived from COVID-19 patients on the BBB integrity in vitro. We also performed a comprehensive analysis of the cytokine and chemokine profiles in the plasma of COVID-19 patients, healthy and recovered individuals. We found significantly increased levels of interferon {gamma}-induced protein 10 kDa (IP-10), hepatocyte growth factor (HGF), and interleukin-18 (IL-18) in the plasma of COVID-19 patients. However, blood plasma from COVID-19 patients did not affect transendothelial electrical resistance (TEER) in iBEC monolayers. Our results demonstrate that COVID-19-associated blood plasma inflammatory factors do not impair BBB integrity directly and suggest that pathological remodelling of BBB during COVID-19 may occur through indirect mechanisms.
  🖺 Full Text HTML: Plasma of COVID-19 patients does not alter electrical resistance of human endothelial blood-brain barrier in vitro.
• Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike -
  Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding domain of spike protein. In contrast, whether antigenic drift occurs in the S2 domain remains largely elusive. Here, we perform a deep mutational scanning experiment to identify S2 mutations that affect binding of SARS-CoV-2 spike to three S2 apex public antibodies. Our results indicate that spatially diverse mutations, including D950N and Q954H, which are observed in Delta and Omicron variants, respectively, weaken the binding of spike to these antibodies. Although S2 apex antibodies are known to be non-neutralizing, we show that they confer partial protection in vivo. We further demonstrate that such in vivo protection activity is diminished by the natural mutation D950N. Overall, this study indicates that the S2 domain of SARS-CoV-2 spike can undergo antigenic drift, which represents a potential challenge for the development of more universal coronavirus vaccines.
  🖺 Full Text HTML: Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike
• Efficient inhibition of fusion inhibitor HY3000 peptide to SARS-CoV-2 emerging EG.5, EG.5.1 and BA.2.86 variants -
  SARS-CoV-2 continues to evolve and spread. Recently, the Omicron EG.5 lineage, bearing an additional F456L mutation in spike (S) protein compared to its ancestor XBB.1.9.2, and its sub-variant EG.5.1, which carries a further Q52H mutation, have raised concerns due to their increased prevalence and extended immune escape properties. Additionally, an alarming variant, BA.2.86, has also garnered global concern because it contains over 30 amino acid mutations in its S protein compared to BA.2, including more than 10 changes in receptor-binding domain (RBD), reminiscent of the appearance of the Omicron variant in late 2021. Therefore, there is an urgent need to assess the effectiveness of current vaccines and therapeutics against EG.5, EG.5.1 and BA.2.86. In our previous work, we reported the design and broad-spectrum antiviral activity of a peptide fusion inhibitor HY3000 against SARS-CoV-2 and its variants including XBB.1.5. Here, we continued to evaluate the inhibitory potency of the HY3000 peptide against the prevailing EG.5 and EG.5.1, as well as XBB.1.16, FL.1.5.1, FY.3 and BA.2.86. Our data indicated that the peptide retained its potent inhibitory activities against these variants, indicating its potential as a good virus fusion inhibitor with broad-spectrum therapeutic effect against current and future SARS-CoV-2 variants. Currently, the HY3000 has been finished in Phase II clinical trial in China and has also been approved to conduct clinical investigation by U.S. Food and Drug Administration (FDA), suggesting a good application prospect against the ongoing COVID-19.
  🖺 Full Text HTML: Efficient inhibition of fusion inhibitor HY3000 peptide to SARS-CoV-2 emerging EG.5, EG.5.1 and BA.2.86 variants
• Inhibiting Glutamine Metabolism Blocks Coronavirus Replication in Mammalian Cells -
  Developing therapeutic strategies against COVID-19 has gained widespread interest given the likelihood that new viral variants will continue to emerge. Here we describe one potential therapeutic strategy which involves targeting members of the glutaminase family of mitochondrial metabolic enzymes (GLS and GLS2), which catalyze the first step in glutamine metabolism, the hydrolysis of glutamine to glutamate. We show three examples where GLS expression increases during coronavirus infection of host cells, and another in which GLS2 is upregulated. The viruses hijack the metabolic machinery responsible for glutamine metabolism to generate the building blocks for biosynthetic processes and satisfy the bioenergetic requirements demanded by the "glutamine addiction" of virus-infected host cells. We demonstrate how genetic silencing of glutaminase enzymes reduces coronavirus infection and that newer members of two classes of small molecule allosteric inhibitors targeting these enzymes, designated as SU1, a pan-GLS/GLS2 inhibitor, and UP4, which is specific for GLS, block viral replication in mammalian epithelial cells. Overall, these findings highlight the importance of glutamine metabolism for coronavirus replication in human cells and show that glutaminase inhibitors can block coronavirus infection and thereby may represent a novel class of anti-viral drug candidates.
  🖺 Full Text HTML: Inhibiting Glutamine Metabolism Blocks Coronavirus Replication in Mammalian Cells
• Inhibition of SARS-CoV-2 Infection in Human Airway Epithelium with a Xeno-Nucleic Acid Aptamer -
  Background: SARS-CoV-2, the agent responsible for the COVID-19 pandemic, enters cells through viral spike glycoprotein binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). Given the lack of effective antivirals targeting SARS-CoV-2, we previously utilized systematic evolution of ligands by exponential enrichment (SELEX) and selected fluoro-arabino nucleic acid (FANA) aptamer R8-9 that was able to block the interaction between the viral receptor-binding domain and ACE2. Methods: Here, we further assessed FANA-R8-9 as an entry inhibitor in contexts that recapitulate infection in vivo. Results: We demonstrate that FANA-R8-9 inhibits spike-bearing pseudovirus particle uptake in cell lines. Then, using an in-vitro model of human airway epithelium (HAE) and SARS-CoV-2 virus, we show that FANA-R8-9 significantly reduces viral infection when added either at the time of inoculation, or several hours later. These results were specific to the R8-9 sequence, not the xeno-nucleic acid utilized to make the aptamer. Importantly, we also show that FANA-R8-9 is stable in HAE culture secretions and has no overt cytotoxic effects. Conclusions: Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.
  🖺 Full Text HTML: Inhibition of SARS-CoV-2 Infection in Human Airway Epithelium with a Xeno-Nucleic Acid Aptamer
• An extended catalytic model to assess changes in risk for multiple reinfections with SARS-CoV-2 -

  Background: The SARS-CoV-2 pandemic has illustrated that monitoring trends in multiple infections can provide insight into the biological characteristics of new variants. Following several pandemic waves, many people have already been infected and reinfected by SARS-CoV-2 and therefore methods are needed to understand the risk of multiple reinfections. Objectives: In this paper, we extended an existing catalytic model designed to detect increases in the risk of reinfection by SARS-CoV-2 to detect increases in the population-level risk of multiple reinfections. Methods: The catalytic model assumes the risk of reinfection is proportional to observed infections and uses a Bayesian approach to fit model parameters to the number of nth infections among individuals whose nth infection was observed at least 90 days before. Using a posterior draw from the fitted model parameters, a 95% projection interval of daily nth infections is calculated under the assumption of a constant nth infection hazard coefficient. An additional model parameter was introduced to consider the increased risk of reinfection detected during the Omicron wave. Validation was performed to assess the model9s ability to detect increases in the risk of third infections. Key Findings: The model parameters converged when applying the model9s fitting and projection procedure to the number of observed third SARS-COV-2 infections in South Africa. No additional increase in the risk of third infection was detected after the increase detected during the Omicron wave. The validation of the third infections method showed that the model can successfully detect increases in the risk of third infections under different scenarios. Limitations: Even though the extended model is intended to detect the risk of nth infections, the method was only validated for detecting increases in the risk of third infections and not for four or more infections. The method is very sensitive to low numbers of nth infections, so it might not be usable in settings with small epidemics, low coverage of testing or early in an outbreak. Conclusions: The catalytic model to detect increases in the risk of reinfections was successfully extended to detect increases in the risk of nth infections and could contribute to future detection of increases in the risk of nth infections by SARS-CoV-2 or other similar pathogens.

  🖺 Full Text HTML: An extended catalytic model to assess changes in risk for multiple reinfections with SARS-CoV-2
• Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort -

  Objective Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. Methods This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits between vaccine availability, and October 29, 2022. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5 to 11, 12 to 17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination. Results The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probably long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 – 44.5) against probable long COVID and 41.7% (15.0– 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 – 61.0]) than children aged 5-11 (23.8% [4.9 –39.0]). VE was higher at 6 months (61.4% [51.0 – 69.6]), but decreased to 10.6% (−26.8 – 37.0%) at 18 months. Discussion This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data. Discussion This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data.

  🖺 Full Text HTML: Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort
• Model-based impact evaluation of new tuberculosis vaccines in aging populations under different modeling scenarios: the case of China. -

  The slow descent in TB burden, the COVID-19 pandemic, along the rise of multidrug-resistant strains of Mycobacterium tuberculosis, seriously threaten TB control and the goals of the End TB strategy. To fight back, several vaccine candidates are under development, with some of them undergoing phases 2B and 3 of the development pipeline. The impact of these vaccines on the general population needs to be addressed using disease-transmission models, and, in a country like China, which last year ranked third in number of cases worldwide, and where the population is undergoing a fast process of demographic aging, the impact of TB vaccination campaigns may depend heavily upon the age of targeted populations and with the mechanistic descriptions of the TB vaccines. For these reasons, transmission models need to capture the coupling between TB dynamics and demographic evolution, as well as to be able to accommodate different mechanistic descriptions of TB vaccine protection. In this work, we studied the potential impact of a new TB vaccine in China targeting adolescents (15-19 y.o.) or elderly people (60-64 y.o.), according to varying vaccine descriptions that represent reasonable mechanisms of action leading to prevention of disease (PoD), or prevention of recurrence (PoR), each of them targetting specific routes to TB disease. To measure the influence of the description of the coupling between transmission dynamics and aging in TB transmission models, we explored two different approaches to compute the evolution of the contact matrices, which relate to the spreading among different age strata. Our results show that the magnitude of model-based impact estimates substantially depends upon the vaccine profile, and it is also strongly related to the modeling approach chosen to describe the time evolution of contact matrices. In spite of these sources of uncertainty, our results also show, in line with previous modeling works, that elder vaccination is a suitable option in China to reduce the incidence of TB.

  🖺 Full Text HTML: Model-based impact evaluation of new tuberculosis vaccines in aging populations under different modeling scenarios: the case of China.
• Time trends and modifiable factors of contact tracing coverage in Geneva, Switzerland, June 2020 to February 2022 -

  Background: Contact tracing has been one of the central non-pharmaceutical interventions implemented worldwide to try to control the spread of Sars-CoV-2, but its effectiveness strongly depends on its ability to detect contacts. Methods: We analysed 1669892 concomitant infections occurring at the same address from June 2020 until February 2022 using an extensive operational database of SARS-CoV-2 tests in Geneva and used permutations statistics to compare the total number of secondary infections occurring at the address with those reported through contact tracing. Results: Manual contact tracing captured on average 41% of the secondary infections, with variation in time from 23% during epidemic peaks to 60% during low epidemic activity. People living in wealthy neighbourhoods were less likely to report contacts (adjusted odds ratio (aOR): 1.6). People living in buildings, compared to people living in single house, were also less likely to report contacts than those living in houses, with an aOR of 1.1 to 3.1 depending on the variant, the size of the building and the presence of shops. This under-reporting of contacts in buildings decreased during periods of mandatory face masking and restriction of private gathering. Conclusions: Contact tracing alone does not detect enough secondary infections to efficiently reduce the propagation of Sars-CoV-2. Public messages and outreach campaigns targeting specific populations, such as those in affluent areas, could enhance coverage. Additionally, measures like wearing face masks, improving ventilation, and implementing gathering restrictions should also be considered to reduce the number of infections occurring during interactions that may not be perceived as high risk.

  🖺 Full Text HTML: Time trends and modifiable factors of contact tracing coverage in Geneva, Switzerland, June 2020 to February 2022
• Scientifically led response plan for future global open-source initiatives related to emergency intervention. -
  The modern era of interconnectedness and rapid technological advancements has ushered in a new paradigm of collaborative problem-solving. Open-source initiatives stand at the helm of this paradigm, driving a culture of shared innovation to tackle global challenges. The global response to the COVID-19 pandemic has magnified the pivotal role of open-source solutions, especially in times of emergency interventions. This guide is designed to assist governmental bodies and organizations in understanding, supporting, and leveraging open-source initiatives to effectively respond to future emergencies. It encapsulates valuable insights and actionable recommendations derived from a thorough examination of past open-source engagements, particularly during the COVID-19 pandemic.
  🖺 Full Text HTML: Scientifically led response plan for future global open-source initiatives related to emergency intervention.
• A Phase 2, randomized, double-blind, placebo-controlled multi-center trial sub-study for the clinical effects of paridiprubart treatment in hospitalized critically ill patients with COVID-19 ARDS -

  Background: Coronavirus disease 2019 (COVID-19) mortality is predominantly due to acute respiratory distress syndrome (ARDS). There are currently limited treatment options for ARDS, a life-threatening condition with different etiologies, secondary to inflammation-induced lung injury. Paridiprubart is a monoclonal antibody that inhibits Toll-like Receptor 4 (TLR4), a key player in ARDS pathophysiology. Methods: This was a prespecified sub-study of a randomized, double-blind, placebo-controlled, Phase 2 trial evaluating the efficacy and safety of paridiprubart in COVID-19 patients with ARDS receiving invasive mechanical ventilation and additional organ support. Efficacy outcomes were 28- and 60-day all-cause mortality, and improvement in COVID-19 severity and ventilation-free days at 28-days post-treatment. Results: Thirteen (13) and twenty (20) patients received paridiprubart and placebo, respectively. The groups were comparable for demographics and baseline parameters, except for higher kidney failure incidence and use of immune modulators and antivirals, and lower corticosteroids use in the paridiprubart group. Mortality at 28-days post-treatment was 7.7% (1/13) in the paridiprubart group versus 40.0% (8/20) for placebo (OR=0.125; 95% CI, 0.013-1.160; P=0.067; P[bootstrap]=0.011). 60-day mortality was 23.1% (3/13) in paridiprubart-treated patients and 45.0% (9/20) in placebo patients (OR=0.367; 95% CI, 0.077-1.749; P=0.208; P[bootstrap]=0.162). Mean survival time was 55.78 days for paridiprubart recipients compared to 41.44 days for placebo patients (HR=0.386; 95% CI, 0.077-1.436; P=0.156; P[bootstrap]=0.083). Although not statistically significant, results for other efficacy measures favored paridiprubart. Incidence of adverse events was similar in both groups. Conclusions: In COVID-19 patients with ARDS requiring invasive ventilation and organ support, paridiprubart was efficacious in preventing mortality and improving clinical outcomes, with no safety concerns.

  🖺 Full Text HTML: A Phase 2, randomized, double-blind, placebo-controlled multi-center trial sub-study for the clinical effects of paridiprubart treatment in hospitalized critically ill patients with COVID-19 ARDS
• Genomic evolution of SARS-CoV-2 variants of concern under in vitro neutralising selection pressure following two doses of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine -
  Aims: To explore viral evolution during in vitro neutralisation using next generation sequencing, and to determine whether sera from individuals immunised with two doses of the Pfizer BioNTech vaccine (BNT162b2) are as effective at neutralising the SARSCoV2 variant of concern (VOC) Delta (B 1.617.2) compared to the earlier lineages Beta (B.1.351) and wildtype (lineage A.2.2) virus. Methods: Using a live virus SARSCoV2 neutralisation assay in Vero E6 cells we determined neutralising antibody titres (nAbT) in 14 participants (vaccine naive (n=2) and post second dose of BNT162b2 vaccination (n=12), median age 45 years [IQR 29 to 65], median time after second dose = 21 days [IQR 19 to 28] against three SARSCoV2 strains: wild-type, Beta and Delta. The determination of nAbT was performed by visual inspection of cytopathic effect (CPE) and inhouse quantitative reverse transcriptase real time quantitative polymerase chain reaction (RTqPCR) to confirm SARS-CoV-2 replication. A total of 110 representative samples including inoculum, neutralisation breakpoints at 72 hrs, negative and positive controls underwent genome sequencing using the Respiratory Viral Oligo Panel version 2 (RVOP) (Illumina Inc. (San Diego, United States of America)) viral enrichment and short read sequencing using (Illumina Inc. (San Diego, United States of America)),(Figure 1). Results: There was a significant reduction in nAbT observed against the Delta and Beta VOC compared with wildtype, 4.4 fold (p = >0.0006) and 2.3 fold (p = 0.0140), respectively (Figure 2). Neutralizing antibodies were not detected in one vaccinated immunosuppressed participant nor the vaccine naive participants (n=2). The highest nAbT against the SARS-CoV-2 variants investigated was obtained from a participant who was vaccinated following SARSCoV2 infection 12 months prior (Table S1). Limited consensus level mutations occurred in the SARS-CoV-2 genome of any lineage during in vitro neutralisation, however, consistent minority allele frequency variants (MFV) were detected in the SARS-CoV-2 polypeptide, spike (S) and membrane protein. Discussion: Significant reductions in nAbT post vaccination were identified, with Delta demonstrating a 4.4 fold reduction. The reduction in nAbT for the VOC Beta has been previously documented, however, limited data is available on vaccine evasion for the Delta VOC, the predominant strain currently circulating worldwide at the time. Studies in high incidence countries may not be applicable to low incidence settings such as Australia as nAbT may be significantly higher in vaccine recipients previously infected with SARSCoV2, as seen in our cohort. Monitoring viral evolution is critical to evaluate the impact of novel SARSCoV2 variants on vaccine effectiveness as mutational profiles in the sub-consensus genome could indicate increases in transmissibility, virulence or allow the development of antiviral resistance.
  🖺 Full Text HTML: Genomic evolution of SARS-CoV-2 variants of concern under in vitro neutralising selection pressure following two doses of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine
• p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein -
  The inhibition of p38 mitogen-activated protein kinase (p38-MAPK) by small molecule chemical inhibitors was previously shown to impair severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, however, mechanisms underlying antiviral activity remains unexplored. In this study, reduced growth of SARS-CoV-2 in p38- knockout Vero cells, together with enhanced viral yield in cells transfected with construct expressing p38, suggested that p38-MAPK is essential for the propagation of SARS-CoV-2. The SARS-CoV-2 was also shown to induce phosphorylation (activation) of p38, at time when transcription/translational activities are considered to be at the peak levels. Further, we demonstrated that p38 supports viral RNA/protein synthesis without affecting viral attachment, entry, and budding in the target cells. In addition, we demonstrated that long-term culture of SARS-CoV-2 in the presence of p38 inhibitor SB203580 does not easily select resistant viral mutants. In conclusion, we provide mechanistic insights on the regulation of SARS-CoV-2 replication by p38 MAPK.
  🖺 Full Text HTML: p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein
• Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera -
  The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.
  🖺 Full Text HTML: Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera

From Clinical Trials

• Study of “Sputnik Lite” for the Prevention of COVID-19 With Altered Antigenic Composition. - Conditions: COVID-19
  Interventions: Biological: “Sputnik Lite” vaccine for the prevention of COVID-19 with altered antigenic composition
  Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
  Not yet recruiting

• Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19 - Conditions: COVID-19, SARS-CoV-2
  Interventions: Biological: Biological: AZD3152; Biological: Biological: Placebo
  Sponsors: AstraZeneca
  Not yet recruiting

• Examining the Function of Cs4 on Post-COVID-19 Disorders - Conditions: Long COVID
  Interventions: Other: Chinese medicine nutritional supplement Cs4
  Sponsors: The University of Hong Kong
  Recruiting

• Amantadine Therapy for Cognitive Impairment in Long COVID - Conditions: Long COVID; Post-COVID19 Condition; Post-Acute COVID19 Syndrome
  Interventions: Drug: Amantadine
  Sponsors: Ohio State University
  Not yet recruiting

• Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia - Conditions: Parosmia
  Interventions: Procedure: Stellate Ganglion Block; Other: Placebo
  Sponsors: Lawson Health Research Institute
  Not yet recruiting

• CPAP Efficacy in Post-COVID Patients With Sleep Apnea - Conditions: COVID-19; Sleep Apnea
  Interventions: Device: Continuous positive airway pressure
  Sponsors: University of Pittsburgh
  Not yet recruiting

• Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2) - Conditions: Systemic Inflammatory Response Syndrome
  Interventions: Biological: Allogeneic thyTreg 5.000.000; Biological: Allogeneic thyTreg 10.000.000
  Sponsors: Hospital General Universitario Gregorio Marañon; Instituto de Salud Carlos III
  Recruiting

• SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19 - Conditions: COVID-19
  Interventions: Drug: SA55 Injection; Other: Placebo for SA55 injection
  Sponsors: Sinovac Life Sciences Co., Ltd.
  Recruiting

• Mind Body Intervention for Long COVID - Conditions: Long COVID; Post-Acute Sequelae of COVID-19; COVID Long-Haul
  Interventions: Behavioral: Mind Body Intervention #1
  Sponsors: Beth Israel Deaconess Medical Center
  Not yet recruiting

• A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects - Conditions: COVID-19
  Interventions: Drug: STI-1558
  Sponsors: Zhejiang ACEA Pharmaceutical Co. Ltd.
  Not yet recruiting

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin) - Conditions: Covid19
  Interventions: Other: Placebo; Drug: Metformin
  Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
  Recruiting

• Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial - Conditions: COVID-19
  Interventions: Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells); Biological: Placebo
  Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention
  Not yet recruiting

• SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People - Conditions: COVID-19
  Interventions: Drug: SA55 nasal spray
  Sponsors: Sinovac Life Sciences Co., Ltd.
  Recruiting

• Tele-physiotherapy on Post-stroke Hemiplegia Patients - Conditions: Hemiplegia; Muscle Spasticity
  Interventions: Other: Conventional Physiotherapy + telephysiotherapty
  Sponsors: Universidad Católica San Antonio de Murcia; Hermanas Hospitalarias del Sagrado Corazón de Jesús; Hospital Universitario Virgen de la Arrixaca
  Completed

• Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom - Conditions: Post-COVID-19 Syndrome
  Interventions: Behavioral: Exercise Therapy; Behavioral: Psychotherapy
  Sponsors: Hannover Medical School; Health Insurance Audi BKK; occupational health service Volkswagen AG; Helmholtz Centre for Infection Research
  Not yet recruiting

From PubMed

• In-silico investigation of 4-nitro-N-1H-pyrazol-3-ylbenzamide towards its potential use against SARS-CoV-2: a DFT, molecular docking and molecular dynamics study - In the present research work, we report the synthesis and characterization of novel pyrazole derivative obtained by the condensation reaction of 4-nitro benzaldehyde group with one equivalent of the 2-amino pyrazole yielding 4-nitro-N-1H-pyrazol-3-ylbenzamide with high yield. The two symmetry-independent molecules (molecule A and molecule B) differ about the central C-N bond, with the dihedral angles between the pyrazole ring system and the nitrobenzene ring being 13.90° and 18.64°,…

• Dimeric ACE2-FC Is Equivalent to Monomeric ACE2 in the Surrogate Virus Neutralization Test - Angiotensin-converting enzyme 2 (ACE2) is the main cellular receptor for the dangerous sarbecoviruses SARS-CoV and SARS-CoV-2. Its recombinant extracellular domain is used to monitor the level of protective humoral immune response to a viral infection or vaccine using the surrogate virus neutralization test (sVNT). Soluble ACE2 is also considered as an option for antiviral therapy potentially insensitive to the changes in the SARS-CoV-2 spike protein. Extensive testing of the samples of…

• Ancestral, Delta, and Omicron (BA.1) SARS-CoV-2 strains are dependent on serine proteases for entry throughout the human respiratory tract - CONCLUSIONS: Our findings demonstrate that entry of Omicron BA.1 SARS-CoV-2 is dependent on serine proteases for entry throughout the respiratory tract.

• DETECTION OF SARS-COV-2 NEUTRALIZING ANTIBODIES IN RETROPHARYNGEAL LYMPH NODE EXUDATES OF WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) FROM NEBRASKA, USA - Disease surveillance testing for emerging zoonotic pathogens in wildlife is a key component in understanding the epidemiology of these agents and potential risk to human populations. Recent emergence of SARS-CoV-2 in humans, and subsequent detection of this virus in wildlife, highlights the need for developing new One Health surveillance strategies. We used lymph node exudate, a sample type that is routinely collected in hunter-harvested white-tailed deer (WTD, Odocoileus virginianus) for…

• Physiological effects of ivabradine in heart failure and beyond - Ivabradine is a pharmacologic agent that inhibits the funny current responsible for determining heart rate in the sinoatrial node. Ivabradine’s clinical potential has been investigated in the context of heart failure since it is associated with reduced myocardial oxygen demand, enhanced diastolic filling, stroke volume, and coronary perfusion time; however, it is yet to demonstrate definitive mortality benefit. Alternative effects of ivabradine include modulation of the…

• The REEP5/TRAM1 complex binds SARS-CoV-2 NSP3 and promotes virus replication - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like other coronaviruses, replicates their genome in virus-induced cytosolic membrane-bound replication organelles (ROs). SARS-CoV-2 promotes the biogenesis of ROs by inducing the rearrangement of endoplasmic reticulum (ER) membranes. NSP3, NSP4, and NSP6 are transmembrane viral non-structural proteins (NSPs) and essential players in the formation of ROs. To understand how these three NSPs work synergistically with host-binding…

• Pupillographic Analysis of COVID-19 Patients: Early and Late Results After Recovery - CONCLUSION: PDs were significantly larger in COVID-19 patients in all light intensities in the 1^(st) month after COVID-19. However, pupillary dilation was transient, and no significant difference was found in the 6^(th) month. We suggest that the transient pupillary dilation may be secondary to the autonomic nervous system dysfunction and/or optic nerve and visual pathways alterations following COVID-19.

• An In Silico Design of Peptides Targeting the S1/S2 Cleavage Site of the SARS-CoV-2 Spike Protein - SARS-CoV-2, responsible for the COVID-19 pandemic, invades host cells via its spike protein, which includes critical binding regions, such as the receptor-binding domain (RBD), the S1/S2 cleavage site, the S2 cleavage site, and heptad-repeat (HR) sections. Peptides targeting the RBD and HR1 inhibit binding to host ACE2 receptors and the formation of the fusion core. Other peptides target proteases, such as TMPRSS2 and cathepsin L, to prevent the cleavage of the S protein. However, research has…

• microRNA-185 Inhibits SARS-CoV-2 Infection through the Modulation of the Host’s Lipid Microenvironment - With the emergence of the novel betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there has been an urgent need for the development of fast-acting antivirals, particularly in dealing with different variants of concern (VOC). SARS-CoV-2, like other RNA viruses, depends on host cell machinery to propagate and misregulate metabolic pathways to its advantage. Herein, we discovered that the immunometabolic microRNA-185 (miR-185) restricts SARS-CoV-2 propagation by…

• Protective versus Pathogenic Type I Interferon Responses during Virus Infections - Following virus infections, type I interferons are synthesized to induce the expression of antiviral molecules and interfere with virus replication. The importance of early antiviral type I IFN response against virus invasion has been emphasized during COVID-19 as well as in studies on the microbiome. Further, type I IFNs can directly act on various immune cells to enhance protective host immune responses to viral infections. However, accumulating data indicate that IFN responses can be harmful…

• Targeting SARS-CoV-2 Macrodomain-1 to Restore the Innate Immune Response Using In Silico Screening of Medicinal Compounds and Free Energy Calculation Approaches - Among the different drug targets of SARS-CoV-2, a multi-domain protein known as NSP3 is a critical element of the translational and replication machinery. The macrodomain-I, in particular, has been reported to have an essential role in the viral attack on the innate immune response. In this study, we explore natural medicinal compounds and identify potential inhibitors to target the SARS-CoV-2-NSP3 macrodomain-I. Computational modeling and simulation tools were utilized to investigate the…

• Mannose-Binding Lectins as Potent Antivirals against SARS-CoV-2 - The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2…

• Atovaquone and Pibrentasvir Inhibit the SARS-CoV-2 Endoribonuclease and Restrict Infection In Vitro but Not In Vivo - The emergence of SARS-CoV-1 in 2003 followed by MERS-CoV and now SARS-CoV-2 has proven the latent threat these viruses pose to humanity. While the SARS-CoV-2 pandemic has shifted to a stage of endemicity, the threat of new coronaviruses emerging from animal reservoirs remains. To address this issue, the global community must develop small molecule drugs targeting highly conserved structures in the coronavirus proteome. Here, we characterized existing drugs for their ability to inhibit the…

• Synthetic Frog-Derived-like Peptides: A New Weapon against Emerging and Potential Zoonotic Viruses - Given the emergence of the coronavirus disease 2019 (COVID-19), zoonoses have raised in the spotlight of the scientific community. Animals have a pivotal role not only for this infection, but also for many other recent emerging and re-emerging viral diseases, where they may represent both intermediate hosts and/or vectors for zoonoses diffusion. Today, roughly two-thirds of human infections are derived from animal origins; therefore, the search for new broad-spectrum antiviral molecules is…

• Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2 - The S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze various substrates, including nucleic acids, proteins, oligopeptides, polysaccharides, and some other molecules. In this study, antibody fractions with affinity for RBD and S-protein (RBD-IgG and S-IgG)…

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