Covid-19 Sentry

Contents

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

From Preprints

• Persistence of disproportionate gender participation in virtual conference Q&A sessions -
  Due to the onset of the COVID-19 pandemic, virtual conferences have become not only more popular and widespread, but necessary. Virtual conferences come with big hopes for inclusion in science. At in-person conferences, there are large gender disparities in Q&A participation, and it is unclear how the shift to virtual would impact gendered Q&A participation. Gendered Q&A participation was tested in four virtual conferences that varied in gender representation and Q&A structured format. In virtual conferences, men continued to take a disproportionate amount of time and space in Q&A sessions. Disproportionate participation did not significantly vary between in-person and virtual formats and did not systematically vary by how the Q&A session was organized. In an all-chat virtual conference, gender differences in volubility were attenuated among higher status academics. Gendered participation and volubility were impacted by which sub-discipline the symposium was in. Future research should focus on the cultural factors that promote or mitigate gender disparities in participation.
  🖺 Full Text HTML: Persistence of disproportionate gender participation in virtual conference Q&A sessions
• The COVID States Project #87: Parent Information Sources and Children COVID Vaccination -
  The path to FDA authorization for vaccines in young children has been complex. On February 1, 2022 Pfizer and BioNTech responded to requests from the Food and Drug Administration (FDA) to seek emergency authorization of their COVID-19 vaccine for children ages 6 months through 4 years on a rolling basis. This authorization would have allowed children to begin receiving the first doses of the COVID-19 vaccine while data comparing two or three course vaccine regimens for children were still being collected. However, on February 11, 2022 the FDA reversed course and announced it would wait for data on the effectiveness of the third dose before granting emergency authorization. Most recently, Moderna announced it was seeking authorization for its vaccine for children under 6 and the FDA has laid out a timeline for examining the authorization requests and data in June. This back and forth has only added to the already confusing information environment for parents surrounding the entire COVID-19 pandemic and decisions about vaccination. Some parents of children under 5 reported frustration to The New York Times at the inconclusive and confusing nature of the vaccine approval process, along with the overall feeling of being left behind while the rest of the world opens up. Others were relieved that they could wait on the decision to vaccinate until more complete data were available. In light of this confusion, it is important to understand where parents are getting information about vaccinating their children against COVID-19. In this report we examine where parents are seeking information about their children’s health and vaccination decision-making, as well as who they discuss these important decisions with. We gathered this information by asking parents to select which sources they use from a list, as well as from an open-ended response question. We find that there is quite a bit of overlap in sources between these two methods.
  🖺 Full Text HTML: The COVID States Project #87: Parent Information Sources and Children COVID Vaccination
• Isolation of bat sarbecoviruses of SARS-CoV-2 clade, Japan -
  Betacoronaviruses have caused 3 outbreaks in the past 2 decades. SARS-CoV-2, in particular, has caused a serious pandemic. As the betacoronaviruses are considered to originate from bats, surveillance of bat betacoronaviruses is crucial for understanding the mechanism of cross-species transition and potential for future outbreaks. We previously detected and characterized a SARS-CoV-2-related sarbecovirus, Rc-o319, from Rhinolophus cornutus in Japan. Here, we detected several bat sarbecoviruses of the SARS-CoV-2 clade from R. cornutus in multiple locations in Japan, and successfully isolated them using Vero/TMPRSS2 cells stably expressing R. cornutus ACE2 (Vero-RcACE2). The coding sequences of S1 region varied among isolates, whereas other genetic regions were highly conserved. Isolates were efficiently grown in Vero-RcACE2 cells, but did not replicate in Vero/TMPRSS2 cells stably expressing human ACE2, suggesting a narrow host range. Further long-term epidemiological studies of sarbecoviruses in wildlife are expected to facilitate the assessment of the risk of their spillover potential.
  🖺 Full Text HTML: Isolation of bat sarbecoviruses of SARS-CoV-2 clade, Japan
• Functional evolution of SARS-COV-2 Spike protein: adaptation on translation and infection via surface charge of spike protein -
  The SARS-COV-2 virus, which causes the COVID-19, is rapidly accumulating mutations to adapt to the hosts. We collected SARS-COV-2 sequence data from the end of 2019 to April 2022 to analyze for their evolutionary features during the pandemic. We found that most of the SARS-COV-2 genes are undergoing negative purifying selection, while the spike protein gene (S-gene) is undergoing rapid positive selection. From the original strain to the alpha, delta and omicron variant types, the Ka/Ks of the S-gene increases, while the Ka/Ks within one variant type decreases over time. During the evolution, the codon usage did not evolve towards optimal translation and protein expression. In contrast, only S-gene mutations showed a remarkable trend on accumulating more positive charges. This facilitates the infection via binding human ACE2 for cell entry and binding furin for cleavage. Such a functional evolution emphasizes the survival strategy of SARS-COV-2, and indicated new druggable target to contain the viral infection. The nearly fully positively- charged interaction surfaces indicated that the infectivity of SARS-COV-2 virus may approach a limit.
  🖺 Full Text HTML: Functional evolution of SARS-COV-2 Spike protein: adaptation on translation and infection via surface charge of spike protein
• Human Surfactant Protein D Facilitates SARS-CoV-2 Pseudotype Binding and Entry in DC-SIGN Expressing Cells, and Downregulates Spike protein Induced Inflammation -
  Pattern recognition receptors are crucial for innate anti-viral immunity, including C-type lectin receptors. Two such examples are Lung surfactant protein D (SP-D) and Dendritic cell-specific intercellular adhesion molecules-3 grabbing non-integrin (DC-SIGN) which are soluble and membrane-bound C-type lectin receptors, respectively. SP-D has a crucial immune function in detecting and clearing pulmonary pathogens; DC-SIGN is involved in facilitating dendritic cell interaction as an antigen-presenting cell with naive T cells to mount an anti-viral immune response. Both SP-D and DC-SIGN have been shown to interact with various viruses, including HIV-1, Influenza A virus and SARS-CoV-2. SARS-CoV-2 is an enveloped RNA virus that causes COVID-19. A recombinant fragment of human SP-D (rfhSP-D) comprising of -helical neck region, carbohydrate recognition domain, and eight N-terminal Gly-X-Y repeats has been shown to bind SARS-CoV-2 Spike protein and inhibit SARS-CoV-2 replication by preventing viral entry in Vero cells and HEK293T cells expressing ACE2. DC-SIGN has also been shown to act as a cell surface receptor for SARS-CoV-2 independent of ACE2. Since rfhSP-D is known to interact with SARS-CoV-2 Spike protein and DC-SIGN, this study was aimed at investigating the potential of rfhSP-D in modulating SARS-CoV-2 infection. Coincubation of rfhSP-D with Spike protein improved the Spike Protein: DC- SIGN interaction. Molecular dynamic studies revealed that rfhSP-D stabilised the interaction between DC-SIGN and Spike protein. Cell binding analysis with DC-SIGN expressing HEK 293T and THP- 1 cells and rfhSP-D treated SARS-CoV-2 Spike pseudotypes confirmed the increased binding. Furthermore, infection assays using the pseudotypes revealed their increased uptake by DC-SIGN expressing cells. The immunomodulatory effect of rfhSP-D on the DC-SIGN: Spike protein interaction on DC-SIGN expressing epithelial and macrophage-like cell lines was also assessed by measuring the mRNA expression of cytokines and chemokines. The RT-qPCR analysis showed that rfhSP-D treatment downregulated the mRNA expression levels of pro-inflammatory cytokines and chemokines such as TNF-, IFN-, IL-1{beta}, IL- 6, IL-8, and RANTES (as well as NF-{kappa}B) in DC-SIGN expressing cells challenged by Spike protein. Furthermore, rfhSP-D treatment was found to downregulate the mRNA levels of MHC class II in DC expressing THP-1 when compared to the untreated controls. We conclude that rfhSP-D helps stabilise the interaction of SARS- CoV-2 Spike protein and DC-SIGN and increases viral uptake by macrophages via DC-SIGN, suggesting an additional role for rfhSP-D in SARS-CoV-2 infection.
  🖺 Full Text HTML: Human Surfactant Protein D Facilitates SARS-CoV-2 Pseudotype Binding and Entry in DC-SIGN Expressing Cells, and Downregulates Spike protein Induced Inflammation
• Modelling long-term COVID-19 hospital admission dynamics using immune protection waning data -

  Immune waning is key to the timely anticipation of COVID-19 long-term dynamics. We assess the impact of periodic vaccination campaigns using a compartmental epidemiological model with multiple age structures and parameterised using empiric time-dependent vaccine protection data. Despite the inherent uncertainty, we show that vaccination on its own, especially if restricted to individuals over 60 years old, seems insufficient to prevent a large number of hospital admissions.

  🖺 Full Text HTML: Modelling long-term COVID-19 hospital admission dynamics using immune protection waning data
• A SCID mouse model to evaluate the efficacy of antivirals against SARS-CoV-2 infection -
  Ancestral SARS-CoV-2 lacks the intrinsic ability to bind to the mouse ACE2 receptor and therefore establishment of SARS-CoV-2 mouse models has been limited to the use of mouse-adapted viruses or genetically modified mice. Interestingly, some of the variants of concern, such as the beta B.1.351 variant, show an improved binding to the mouse receptor and hence better replication in different Wild type (WT) mice species. Here, we desribe the establishment of SARS-CoV-2 beta B.1.351 variant infection model in male SCID mice as a tool to assess the antiviral efficacy of potential SARS-CoV-2 small molecule inhibitors. Intranasal infection of male SCID mice with 105 TCID50 of the beta B.1.351 variant resulted in high viral loads in the lungs and moderate signs of lung pathology on day 3 post-infection (pi). Treatment of infected mice with the antiviral drugs Molnupiravir (200 mg/kg, BID) or Nirmatrelvir (300 mg/kg, BID) for 3 consecutive days significantly reduced the infectious virus titers in the lungs by 1.9 and 3.8 log10 TCID50/mg tissue, respectively and significantly improved lung pathology. Together, these data demonstrate the validity of this SCID mice/beta B.1.351 variant infection model as a convenient preclinical model for assessment of potential activity of antivirals against SARS-CoV-2.
  🖺 Full Text HTML: A SCID mouse model to evaluate the efficacy of antivirals against SARS-CoV-2 infection
• SARS-CoV-2 Omicron Variant Wave in India: Advent, Phylogeny and Evolution -
  SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was responsible for disease in patients without comorbidity(97%), while Omicron BA.2 caused disease primarily in those with comorbidity(77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could possibly be due to evolutionary trade-off and explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2.
  🖺 Full Text HTML: SARS-CoV-2 Omicron Variant Wave in India: Advent, Phylogeny and Evolution
• A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants -
  Vaccines are a cornerstone in COVID-19 pandemic management. Here, we compare immune responses to and preclinical efficacy of the mRNA vaccine BNT162b2, an adenovirus-vectored spike vaccine, and the live-attenuated-virus vaccine candidate sCPD9 after single and double vaccination in Syrian hamsters. All regimens containing sCPD9 showed superior efficacy. The robust immunity elicited by sCPD9 was evident in a wide range of immune parameters after challenge with heterologous SARS-CoV-2 including rapid viral clearance, reduced tissue damage, fast differentiation of pre- plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue. Our results demonstrate that use of live-attenuated vaccines may offer advantages over available COVID-19 vaccines, specifically when applied as booster, and may provide a solution for containment of the COVID-19 pandemic.
  🖺 Full Text HTML: A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants
• AI-based search for convergently expanding, advantageous mutations in SARS-CoV-2 by focusing on oligonucleotide frequencies -
  Among mutations that occur in SARS-CoV-2, efficient identification of mutations advantageous for viral replication and transmission is important to characterize and defeat this rampant virus. Mutations rapidly expanding frequency in a viral population are candidates for advantageous mutations, but neutral mutations hitchhiking with advantageous mutations are also likely to be included. To distinguish these, we focus on mutations that appear to occur independently in different lineages and expand in frequency in a convergent evolutionary manner. Batch-learning SOM (BLSOM) can separate SARS-CoV-2 genome sequences according by lineage from only providing the oligonucleotide composition. Focusing on remarkably expanding 20-mers, each of which is only represented by one copy in the viral genome, allows us to correlate the expanding 20-mers to mutations. Using visualization functions in BLSOM, we can efficiently identify mutations that have expanded remarkably both in the Omicron lineage, which is phylogenetically distinct from other lineages, and in other lineages. Most of these mutations involved changes in amino acids, but there were a few that did not, such as an intergenic mutation.
  🖺 Full Text HTML: AI-based search for convergently expanding, advantageous mutations in SARS-CoV-2 by focusing on oligonucleotide frequencies
• Hijacking of Cellular Functions by Severe Acute Respiratory Syndrome Coronavirus-2. Permeabilization and Polarization of the Host Lipid Membrane by Viroporins. -
  As all viral infections, SARS-CoV-2 acts at multiple levels hijacking fundamental cellular functions and assuring its replication and immune system evasion. In particular, it has been observed that the viral 3’ Open Reading Frame (ORF3) codes for a hydrophobic protein which embeds in the cellular membrane, where it acts as an ion viroporin and is related to strong inflammatory response. Here we report equilibrium and enhanced sampling molecular dynamic simulation of the SARS-CoV-2 ORF3 in a model lipid bilayer, showing how the protein permeabilizes the lipid membrane, via the formation of a water channel, which in turn assures ion transport. We report the free energy profile for both K+ and Cl- transfer from the cytosol to the extracellular domain. The important role of ORF3 in the viral cycle, and its highly conservation among coronaviruses, may also make it a target of choice for future antiviral development, further justifying the elucidation of its mechanism at the atomistic level.
  🖺 Full Text HTML: Hijacking of Cellular Functions by Severe Acute Respiratory Syndrome Coronavirus-2. Permeabilization and Polarization of the Host Lipid Membrane by Viroporins.
• Fatty Acid Synthase inhibitor TVB-3166 prevents S-acylation of the Spike protein of human coronaviruses. -
  The Spike protein of SARS-CoV2 and other coronaviruses mediate host cell entry and are S-acylated on multiple phylogenetically conserved cysteine residues. Multiple protein acyltransferase enzymes of the ZDHHC family have been reported to modify Spike proteins post-translationally. Using resin-assisted capture mass spectrometry, we demonstrate that the Spike protein is S-acylated in SARS-CoV2 infected human and monkey cells. We further show that increased abundance of the human acyltransferase ZDHHC5 results in increased S-acylation of the SARS-CoV2 Spike protein, whereas ZDHHC5 knockout cells had a 40% reduction in the incorporation of an alkynyl-palmitate using click chemistry detection. We also find that the S-acylation of the Spike protein is not limited to palmitate, as clickable versions of myristate and stearate were also found on the immunocaptured protein. Yet, ZDHHC5 was highly selective for palmitate, suggesting that other ZDHHC enzymes mediated the incorporation of other fatty acyl chains. Thus, since multiple ZDHHC isoforms may modify the Spike protein, we examined the ability of the fatty acid synthase inhibitor TVB-3166 to prevent the S-acylation of the Spike proteins of SARS-CoV-2 and human CoV-229E. Treating cells with TVB-3166 inhibited S-acylation of ectopically expressed SARS-CoV2 Spike and attenuated the ability of SARS-CoV2 and human CoV-229E to spread in vitro. Additionally, treatment of mice with a comparatively low dose of TVB-3166 promoted survival from an otherwise fatal murine coronavirus infection. Our findings further substantiate the necessity of CoV Spike protein S-acylation and the potential use of fatty acid synthase inhibitors.
  🖺 Full Text HTML: Fatty Acid Synthase inhibitor TVB-3166 prevents S-acylation of the Spike protein of human coronaviruses.
• Elucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease -

  DNA methylation commonly occurs at cytosine-phosphate-guanine sites (CpGs) that can serve as biomarkers for many diseases. We analyzed whole genome sequencing data to identify DNA methylation quantitative trait loci (mQTLs) in 4,126 Framingham Heart Study participants. Our mQTL mapping identified 94,362,817 cis-mQTLvariant-CpG pairs (for 210,156 unique autosomal CpGs) at P<1e-7 and 33,572,145 trans-mQTL variant-CpG pairs (for 213,606 unique autosomal CpGs) at P<1e-14. Using cis-mQTL variants for 1,258 CpGs associated with seven cardiovascular disease risk factors, we found 104 unique CpGs that colocalized with at least one cardiovascular disease trait. For example, cg11554650 (PPP1R18) colocalized with type 2 diabetes, driven by a single nucleotide polymorphism (rs2516396). We performed Mendelian randomization (MR) analysis and demonstrated 58 putatively causal relations of CVD risk factor-associated CpGs to one or more risk factors (e.g., cg05337441 [APOB] with LDL; MR P=1.2e-99, and 17 causal associations with coronary artery disease (e.g. cg08129017 [SREBF1] with coronary artery disease; MR P=5e-13). We also showed that three CpGs, e.g., cg14893161 (PM20D1), are putatively causally associated with COVID-19 severity. To assist in future analyses of the role of DNA methylation in disease pathogenesis, we have posted a comprehensive summary data set in the National Heart, Lung, and Blood Institute9s BioData Catalyst.

  🖺 Full Text HTML: Elucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease
• Assessment of oxidative stress markers in elderly patients with SARS-CoV-2 infection and potential prognostic implications. An observational study -

  The aim of the study was to evaluate the correlation of plasma levels of thiobarbituric acid reactive substances (TBARS) and reduced thiols with morbidity, mortality and immune response in SARS-CoV-2 infection. This was an observational study that included inpatients with SARS-CoV-2 infection greater than 65 years old. Individuals were followed up until 12 months after hospital discharge. Demographic, clinical and laboratory variables were collected. Plasma levels of TBARS and reduced thiols were quantified as a measure of lipid and protein oxidation, respectively. Events of interest (fatal and non-fatal) were quantified at hospital discharge, third, sixth and twelfth-month post- discharge. The outcomes were differences in oxidative stress markers between groups of interest and time to a negative RT-qPCR and to significant anti-SARS-CoV-2 IgM titers. There were 61 patients (57% women) with a mean age of 83 years old. Patients with higher levels of TBARS and lower levels of reduced thiols had more risk of fatal and non-fatal events between admission and the first 12 months post-discharge. The presence of any event (fatal or non-fatal) at the end of the first 12 months post-discharge was correlated with TBARS levels, anti-SARS-CoV-2 IgM titers, lactate dehydrogenase, platelet count and neutrophil and lymphocyte count. We found a correlation between plasma reduced thiols and time to achieve significant anti-SARS-CoV-2 IgM titers. Assessment of some parameters related to oxidative stress could help to identify groups of patients with a higher risk of morbidity and mortality during and after SARS-CoV-2 infection.

  🖺 Full Text HTML: Assessment of oxidative stress markers in elderly patients with SARS-CoV-2 infection and potential prognostic implications. An observational study
• Effects of social support on depression risk during the COVID-19 pandemic: What support types and for whom? -

  Background. Rates of depression have increased worldwide during the COVID-19 pandemic. One known protective factor for depression is social support, but more work is needed to quantify the extent to which social support can reduce depression risk during the COVID-19 pandemic, and specifically to identify which types of support are most helpful during a pandemic, and who might benefit most. Methods. Data were obtained from participants in the All of Us Research Program who responded to the COVID-19 Participant Experience (COPE) survey administered monthly from May 2020 to July 2020 (N=69,066, 66% female). Social support was assessed using 10 items from the RAND Medical Outcome Study (MOS) Social Support Survey which measures emotional/informational support (e.g., someone to confide in or talk to about yourself or your problems), positive social interaction support (e.g., someone to do things with to help you get your mind off things), and tangible support (e.g., someone to help with daily chores if sick). Elevated depression symptoms were defined based on having a moderate-to-severe (≥10) score on the Patient Health Questionnaire (PHQ-9). Mixed-effects logistic regression models were used to separately test the association between overall social support and its subtypes with depression, adjusting for age, sex, race, ethnicity, and socioeconomic factors. We then tested interactions between social support and effect modifiers: age, sex, pre-pandemic mood disorder, and pandemic-related stressors (e.g., financial insecurity). Results. Approximately 16% of the sample experienced elevated depressive symptoms. Overall social support was associated with significantly reduced odds of depression (adjusted odds ratio, aOR [95% CI]=0.44 [0.42-0.45]). Among subtypes, emotional/informational support (aOR=0.42 [0.41-0.43]) and positive social interactions (aOR=0.43 [0.41-0.44]) showed the largest protective associations with depression, followed by tangible support (aOR=0.63 [0.61-0.65]). Sex, age, and pandemic-related financial stressors were statistically significant modifiers of the association between social support and depression. Conclusions. Individuals reporting higher levels of social support were at reduced risk of depression during the early months of the COVID-19 pandemic. The perceived availability of emotional support and positive social interactions, more so than tangible support, was key. Individuals more vulnerable to depression (e.g., women, younger individuals, and those experiencing financial stressors) may particularly benefit from enhanced social support, supporting a precision prevention approach.

  🖺 Full Text HTML: Effects of social support on depression risk during the COVID-19 pandemic: What support types and for whom?

From Clinical Trials

• The Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19 - Condition:   COVID-19
  Intervention:   Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)
  Sponsors:   University of California, Irvine;   Hudson Valley Healing Arts Center
  Not yet recruiting

• Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents - Condition:   COVID-19
  Interventions:   Drug: STI-9199;   Drug: Placebo
  Sponsor:  
  Sorrento Therapeutics, Inc.
  Not yet recruiting

• A Study to Evaluate the Safety and Immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in Population 18 Years Old of Age and Above - Condition:   COVID-19
  Intervention:   Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsors:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Shulan (Hangzhou) Hospital
  Recruiting

• Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above - Condition:   COVID-19
  Interventions:   Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsors:  
  China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Hunan Provincial Center for Disease Control and Prevention
  Recruiting

• Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19 - Condition:   COVID-19
  Intervention:   Radiation: [18F]DPA-714 positron emission tomography (PET) scan
  Sponsors:   Amsterdam UMC, location VUmc;   ZonMw: The Netherlands Organisation for Health Research and Development
  Enrolling by invitation

• Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation - Condition:   COVID-19
  Intervention:   Drug: Palbociclib
  Sponsor:   biotx.ai GmbH
  Active, not recruiting

• Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older - Condition:   COVID-19
  Interventions:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo
  Sponsor:   CanSino Biologics Inc.
  Not yet recruiting

• Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older - Condition:   COVID-19
  Interventions:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo
  Sponsor:   CanSino Biologics Inc.
  Not yet recruiting

• THEMBA II T-Cell Vaccine: Vaccination With saRNA COVID-19 Vaccines - Condition:   COVID-19
  Interventions:   Biological: AAHI-SC2 Vaccine;   Biological: AAHI- SC3 Vaccine;   Biological: EUA or approved vaccine
  Sponsor:   ImmunityBio, Inc.
  Recruiting

• To Evaluate SSD8432/Ritonavir in Adults With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SSD8432 dose;   Drug: SSD8432 placebo
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Not yet recruiting

• The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Chinese herbal medicine
  Sponsor:  
  Hong Kong Baptist University
  Not yet recruiting

• Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Placebo-Controlled, Phase II Clinical Study - Condition:   COVID-19
  Interventions:   Drug: SSD8432 dose1;   Drug: SSD8432 dose2;   Drug: SSD8432Placebo
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Not yet recruiting

• To Evaluate SSD8432/ Ritonavir in Adults With COVID-19 - Condition:   COVID-19 Patients
  Interventions:   Drug: SSD8432 dose 1/Ritonavir;   Drug: SSD8432 dose 2/Ritonavir
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Recruiting

• Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine - Condition:   COVID-19 Pandemic
  Interventions:   Biological: A Lyophilized COVID-19 mRNA Vaccine;   Biological: Placebo
  Sponsor:   Wuhan Recogen Biotechnology Co., Ltd.
  Not yet recruiting

• Home-based Exercise Program in Patients With the Post-COVID-19 Condition - Conditions:   Long COVID;   Post-acute COVID-19 Syndrome
  Intervention:   Other: Home- based physical training
  Sponsor:   University of Sao Paulo
  Not yet recruiting

From PubMed

• Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS- COV-2 cell entry facilitator spike protein - CONCLUSION: The compounds, Quercetin and Genistein, can inhibit the TMPRSS2 guided priming of the spike protein. The compounds could reduce the interaction of the host cell with the type I transmembrane glycoprotein to prevent the entry of the virus. The critical finding is that compared to Genistein, Quercetin exhibits higher binding affinity with the catalytic unit of TMPRSS2 and forms a stable complex with the target. Thus, enhancing our innate immunity by consuming foods rich in Quercetin…

• Famotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm - CONCLUSIONS: These observations reveal a previously unidentified vagus nerve-dependent anti-inflammatory effect of famotidine in the setting of cytokine storm which is not replicated by high dosages of other H2R antagonists in clinical use. Because famotidine is more potent when administered intrathecally, these findings are also consistent with a primarily central nervous system mechanism of action.

• Repurposing the natural compounds as potential therapeutic agents for COVID-19 based on the molecular docking study of the main protease and the receptor-binding domain of spike protein - Severe acute respiratory syndrome coronavirus (SARS-CoV-2) enters the cell by interacting with the human angiotensin- converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of spike (S) protein. In the cell, the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme is essential for its life cycle and controls coronavirus replication. Therefore, the S-RBD and 3CLpro are hot targets for drug discovery against SARS-CoV-2. This study was to identify repurposing drugs…

• Polygoni multiflori radix extracts inhibit SARS-CoV-2 pseudovirus entry in HEK293T cells and zebrafish larvae - CONCLUSIONS: Our results indicate that the water and ethanol extracts of PMR have an inhibitory effect on SARS-CoV-2 pseudovirus host-cell entry. Furthermore, EGCG might be an active component of PMR, which blocks SARS-CoV-2 entry to cells. Taken together, our findings suggest that PMR might be considered as a potential treatment for COVID-19.

• How SARS-CoV-2 dodges immune surveillance and facilitates infection: an analytical review - INTRODUCTION: Effective treatments for the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are limited. The virus has evolved strategies to evade the immune system or hijack immune responses to facilitate infection and escape immune surveillance. Mechanistically, SARS-CoV-2 takes advantage of TLR4 and cytokine-induced integrins to promote its entrance into the cell. Furthermore, the activation of pattern recognition receptors (PRR)-mediated signaling pathways is…

• Screening for inhibitors against SARS-CoV-2 and its variants - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, generating new variants that pose a threat to global health; therefore, it is imperative to obtain safe and broad-spectrum antivirals against SARS-CoV-2 and its variants. To this end, we screened compounds for their ability to inhibit viral entry, which is a critical step in virus infection. Twenty compounds that have been previously reported to inhibit SARS-CoV-2 replication were tested by using pseudoviruses…

• Nitric-oxide enriched plasma-activated water inactivates 229E coronavirus and alters antiviral response genes in human lung host cells - The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach…

• Aerosol Transmission of the Pandemic SARS-CoV-2 and Influenza A Virus Was Blocked by Negative Ions - The pandemic of respiratory diseases, such as coronavirus disease 2019 (COVID-19) and influenza, has imposed significant public health and economic burdens on the world. Wearing masks is an effective way to cut off the spread of the respiratory virus. However, due to cultural differences and uncomfortable wearing experiences, not everyone is willing to wear masks; there is an urgent need to find alternatives to masks. In this study, we tested the disinfection effect of a portable ionizer on…

• Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L - Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanisms and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the…

• Novel Insights Into the Sulfated Glucuronic Acid-Based Anti-SARS-CoV-2 Mechanism of Exopolysaccharides From Halophilic Archaeon Haloarcula hispanica - The pandemic caused by SARS-CoV-2 is the most widely spread disease in the 21st century. Due to the continuous emergence of variants across the world, it is necessary to expand our understanding of host-virus interactions and explore new agents against SARS-CoV-2. In this study, it was found exopolysaccharides (EPSs) from halophilic archaeon Haloarcula hispanica ATCC33960 can bind to the spike protein of SARS-CoV-2 with the binding constant K(D) of 2.23 nM, block the binding of spike protein to…

• Antiviral phytocompounds “ellagic acid” and “(+)-sesamin” of Bridelia retusa identified as potential inhibitors of SARS-CoV-2 3CL pro using extensive molecular docking, molecular dynamics simulation studies, binding free energy calculations, and bioactivity prediction - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected billions and has killed millions to date. Studies are being carried out to find therapeutic molecules that can potentially inhibit the replication of SARS-CoV-2. 3-chymotrypsin-like protease (3CL pro) involved in the polyprotein cleavage process is believed to be the key target for viral replication, and hence is an attractive target for the discovery of antiviral molecules. In the present study, we aimed to identify…

• ORF8 protein of SARS-CoV-2 reduces male fertility in mice - As one of the most rapidly evolving proteins of the genus Betacoronavirus, ORF8’s function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by ROS scavenger and ER-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion，we examined the plasma samples of COVID-19 convalescent patients and found that the…

• Recommendations for the management of drug-drug interactions between the COVID-19 antiviral nirmatrelvir/ritonavir (Paxlovid^® ) and comedications - The Covid-19 antiviral nirmatrelvir/ritonavir (NMV/r) (Paxlovid^(®) ) has been granted authorization or approval in several countries for the treatment of patients with mild to moderate COVID-19 at high risk of progression to severe disease and with no requirement for supplemental oxygen. NMV/r will be primarily administered outside the hospital setting as a 5-day course oral treatment. The ritonavir component boosts plasma concentrations of nirmatrelvir through the potent and rapid inhibition…

• Molecular Interactions and Inhibition of the SARS-CoV-2 Main Protease by a Thiadiazolidinone Derivative - We report molecular interactions and inhibition of the main protease (M^(Pro) ) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore conformational dynamics of M^(Pro) via docking protocols and molecular dynamics (MD) simulations in all-atom detail. We reveal local and global dynamics of M^(Pro) in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC(50) value of 1.39 ± 0.22 μM,…

• Conducting the RBD of SARS-CoV-2 Omicron Variant with Phytoconstituents from Euphorbia dendroides to Repudiate the Binding of Spike Glycoprotein Using Computational Molecular Search and Simulation Approach - (1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1-7),…

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