- Connected Despite Lockdown: The Role of Social Interactions and Social Media Use in Wellbeing -
Humans are social beings, but during the COVID-19 pandemic, people around the world are periodically in lockdown and are required to try to physically distance themselves from others. The resultant limitation of face-to-face interactions presents a challenge to wellbeing. During periods of lockdown, people can, however, still connect to others via technology, but it is unknown whether such interactions offer benefits comparable to face-to-face interactions. In the present study, we examined how different ways of interacting with others impacted wellbeing during a period of lockdown in the United Kingdom. In a 30-day diary study conducted in April-June 2020, 110 adults reported the time they spent daily on face-to-face interactions and technology-mediated communication (video, phone, text) with different interaction partners. They also indicated the time they spent on active and passive social media use and their end-of- day wellbeing. Multilevel regressions indicated that more face-to-face interactions both within and outside of one’s household positively predicted wellbeing, while technology-mediated communication had less consistent positive effects. Additionally, more active and less passive social media use predicted better wellbeing. These results highlight the complexity of benefits of different kinds of social interactions during lockdown in the COVID-19 pandemic and point to the importance of taking into account communication channels, interaction partners, and how people use social media when studying the effects of connecting to others.
- Ostracism and Conspiracy Beliefs About COVID-19: Personality and Existential Underlying Mechanisms in a Quote Sampling Study During the First Wave of the Pandemic -
Aims: This paper examines the association between ostracism and endorsement of COVID-19 conspiracy theories, the mediating role of sense of vulnerability, self-uncertainty and individual/collective narcissism and the moderating role of conspiracy mentality. Methods: Participants were recruited in the United Kingdom via quote sampling (N=895). Power analysis and sample size checks were conducted beforehand. A cross-sectional design was deployed and in subsequent analyses we controlled for demographic variables. Results: Ostracism positively predicted endorsement of COVID-19 conspiracy theories and this association was mediated by sense of vulnerability, self-uncertainty, meaning seek, individual and collective narcissism. Furthermore, conspiracy mentality moderated the relationship between ostracism and COVID-19 conspiracy beliefs. Conclusion: Our study expands on the still very few and scarce research on ostracism and conspiracy theories and building on existing findings, it explores further underlying personality and existential variables that explain this relationship. Theoretical and societal implications are discussed.
- Bayesian Inference of Dependent Population Dynamics in Coalescent Models -
The coalescent is a powerful statistical framework that allows us to infer past population dynamics leveraging the ancestral relationships reconstructed from sampled molecular sequence data. In many biomedical applications, such as in the study of infectious diseases, cell development, and tumorgenesis, several distinct populations share evolutionary history and therefore become dependent. The inference of such dependence is a highly important, yet a challenging problem. With advances in sequencing technologies, we are well positioned to exploit the wealth of high-resolution biological data for tackling this problem. Here, we present a novel probabilistic model that relies on jointly distributed Markov random fields. We use this model to estimate past population dynamics of dependent populations and to quantify their degree of dependence. An essential feature of our approach is the ability to track the time-varying association between the populations while making minimal assumptions on their functional shapes via Markov random field priors. We provide nonparametric estimators, extensions of our base model that integrate multiple data sources, and fast scalable inference algorithms. We test our method using simulated data under various dependent population histories and demonstrate the utility of our model in shedding light on evolutionary histories of different variants of SARS- CoV-2.
- Host-directed therapy with 2-Deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2 -
Rhinoviruses (RVs) and coronaviruses (CoVs) upregulate host cell metabolic pathways including glycolysis to meet their bioenergetic demands for rapid multiplication. Using the glycolysis inhibitor 2-deoxy-D-glucose (2-DG), we confirm the dose-dependent inhibition of minor- and major-receptor group RV replication. We demonstrate that 2-DG suppresses viral positive- as well as negative-strand RNA synthesis, resulting in lower amounts of progeny virus and RV-mediated cell death. In tissue culture with physiologic glucose levels, 2-DG has a pronounced antiviral effect. Further, assessment of 2-DG’s intracellular kinetics revealed that the active intermediate, 2-DG6P, is stored intracellularly for several hours. Our concurrent study of 2-DG’s impact on pandemic SARS-CoV-2 and endemic HCoVs demonstrated a significant reduction in viral load. Collectively, these results suggest 2-DG to be a broad-spectrum antiviral.
- RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity -
The spread of SARS-CoV-2 has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges due to subsequent waves and long-term consequences of great concern. Here we charted the molecular basis of COVID-19 pathogenesis, by analysing patients’ immune response at single-cell resolution across disease course and severity. This approach uncovered cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identified a severity-associated activation of the receptor for advanced glycation endproduct (RAGE) pathway in monocytes. In vitro experiments confirmed that monocytes bind the SARS-CoV-2 S1-RBD via RAGE and that RAGE-Spike interactions drive monocyte infection. Our results demonstrate that RAGE is a novel functional receptor of SARS-CoV-2 contributing to COVID-19 severity.
- Predicting recognition between T cell receptors and epitopes using contextualized motifs -
We introduce TCRconv, a deep learning model for predicting recognition between T-cell receptors and epitopes. TCRconv uses a deep protein language model and convolutions to extract contextualized motifs and provides state-of-the- art TCR-epitope prediction accuracy. Using TCR repertoires from COVID-19 patients, we demonstrate that TCRconv can provide insight into T-cell dynamics and phenotypes during the disease.
- Genomic diversity of SARS-CoV-2 can be accelerated by a mutation in the nsp14 gene -
Nucleotide substitution rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is relatively low compared to the other RNA viruses because coronaviruses including SARS-CoV-2 encode non-structural protein 14 (nsp14) that is an error-correcting exonuclease protein. In this study, to understand genome evolution of SARS-CoV-2 in the current pandemic, we examined mutations of SARS-CoV-2 nsp14 which could inhibit its error-correcting function. First, to obtain functionally important sites of nsp14, we examined 62 representative coronaviruses belonging to alpha, beta, gamma, delta, and unclassified coronaviruses. As a result, 99 out of 527 amino acid sites of nsp14 were evolutionarily conserved. We then examined nsp14 sequences obtained from 28,082 SARS-CoV-2 genomes and identified 6 amino acid changes in nsp14 mutants that were not detected in the 62 representative coronaviruses. We examined genome substitution rates of these mutants and found that an nsp14 mutant with a proline to leucine change at position 203 (P203L) showed a higher substitution rate (35.9 substitutions/year) than SARS-CoV-2 possessing wild-type nsp14 (19.8 substitutions/year). We confirmed that the substitution rate of the P203L is significantly higher than those of other variants containing mutations in structural proteins. Although the number of SARS-CoV-2 variants containing P203L mutation of nsp14 is limited (26), these mutants appeared at least 10 times independently in the current pandemic. These results indicated that the molecular function of nsp14 is important for survival of various coronaviruses including SARS-CoV-2 and that some mutations such as P203L of nsp14 inhibiting its error-correcting function are removed rapidly due to their deleterious effects.
- The impact of heating, ventilation and air conditioning (HVAC) design features on the transmission of viruses, including SARS-CoV-2: an overview of reviews -
Background: The 2019 novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak was declared a pandemic by the World Health Organization (WHO) in March 2020. Almost two years later (early-February 2022), the WHO reported over 383 million cases of the disease caused by the virus with over 5.6 million deaths worldwide. Debate regarding routes of transmission was substantial early in the pandemic; however, airborne transmission emerged as an important consideration. Infectious airborne agents can spread within the built environment through heating, ventilation, and air conditioning (HVAC) systems. Multiple features of HVAC systems can influence transmission (e.g., ventilation, filtration, ultraviolet radiation, humidity). Understanding how HVAC features influence airborne transmission is critical to mitigate the spread of infectious agents. Objective: Given airborne transmission of SARS- CoV-2, an overview of reviews was conducted to understand what is already known from the scientific literature about how virus transmission may be affected by HVAC design features in the built environment. Methods: Ovid MEDLINE and Compendex were searched from inception to January 2021. Two reviewers independently screened titles and abstracts and full text of potentially relevant reviews, using a priori inclusion criteria. Inclusion criteria were systematic reviews examining effects of HVAC design features on virus transmission. Two reviewers independently assessed methodological quality using AMSTAR2. Results: Searching identified 361 citations, 45 were potentially relevant, and 7 were included. Reviews were published between 2007 and 2021, and included 47 virus studies. Two earlier reviews (2007, 2016) of 21 studies found sufficient evidence that mechanical ventilation (airflow patterns, ventilation rates) plays a role in airborne transmission; however, both found insufficient evidence to quantify minimum mechanical ventilation requirements. One review (2017) of 9 studies examining humidity and indoor air quality found that influenza virus survival was lowest between 40% and 80% relative humidity; authors noted that ventilation rates were a confounding variable. Two reviews (2021) examined mitigation strategies for coronavirus transmission, finding that transmission decreased with increasing temperature and relative humidity. One review (2020) identified 14 studies examining coronavirus transmission in air conditioning systems, finding HVAC systems played a role in virus spread during previous coronavirus outbreaks. One review (2020) examined virus transmission interventions on public ground transportation, finding ventilation and filtration to be effective. Conclusions: Seven reviews synthesizing 47 studies demonstrate a role for HVAC in mitigating airborne virus transmission. Ventilation, humidity, temperature, and filtration can play a role in viability and transmission of viruses, including coronaviruses. Recommendations for minimum standards were not possible due to few studies investigating a given HVAC parameter. This overview examining HVAC design features and their effects on airborne transmission of viruses serves as a starting point for future systematic reviews and identifying priorities for primary research.
- Incidence of Glomerulonephritis after SARS-CoV-2 mRNA Vaccination -
Numerous cases of glomerulonephritis manifesting shortly after SARS-CoV-2 vaccination have been reported, but causality remains unproven. We studied the association between mRNA-based SARS-CoV-2 vaccination and new-onset glomerulonephritis using a nationwide retrospective cohort and case-cohort design. Data from all Swiss pathology institutes processing native kidney biopsies served to calculate incidence of IgA nephropathy, pauci-immune necrotizing glomerulonephritis, minimal change disease and membranous nephropathy. The observed incidence during the vaccination campaign (Jan to Aug 2021) was not different from the expected incidence based on the years 2015 to 2019 (incidence rate ratio 0.86, 95%-credible interval 0.73-1.02) and did not cross the upper boundary of the 95% credible interval for any month. Among 111 patients aged >18 years with newly diagnosed glomerulonephritis between January and August 2021, 38.7% had received at least one vaccine dose before biopsy, compared to 39.5% of the general Swiss population matched for age and calendar-time. The estimated risk ratio for the development of new-onset biopsy-proven glomerulonephritis was 0.97 (95% CI 0.66-1.42, P=0.95) in vaccinated vs. unvaccinated individuals. Patients with glomerulonephritis manifesting within 4 weeks after vaccine did not differ clinically from the rest of the cohort. Results were consistent across all types of glomerulonephritis with the possible exception of minimal change disease. In conclusion, vaccination against SARS-CoV-2 was not associated with new-onset glomerulonephritis in these two complementary studies. Most temporal associations between SARS-CoV-2 vaccination and glomerulonephritis are likely coincidental.
- Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic -
The impact of COVID-19 represents a specific challenge for voluntary transfusional systems sustained by the intrinsic motivations of blood donors. In general, health emergencies can stimulate altruistic behaviors. However, in this context, the same prosocial motivations, besides the personal health risks, could foster the adherence to social distancing rules to preserve collective health and, therefore, discourage blood donation activities. In this work, we investigate the consequences of the pandemic shock on the dynamics of new donors exploiting the individual-level longitudinal information contained in administrative data on the Italian region of Tuscany. We compare the change in new donors’ recruitment and retention during 2020 with respect to the 2017-2019 period, considering donors’ and their municipalities of residence characteristics. Our results show an increment of new donors, with higher growth for older donors. Moreover, we demonstrate that the quality of new donors, as proxied by the frequency of subsequent donations, increased with respect to previous years. Finally, we show that changes in extrinsic motivations, such as the possibility of obtaining a free antibody test or overcoming movement restrictions, cannot explain the documented improvement in performances.
- Unveiling the G4-PAMAM capacity to bind and protect Ang-(1-7) bioactive peptide -
New therapies that allow natural healing processes are required. Such as the endogenous peptide called Angiotensin-(1-7), a safe and effective drug, which is able to re-balance the Renin-Angiotensin system affected during several pathologies, including the new COVID-19; cardiovascular, renal, and pulmonary disease; diabetes; neuropathic pain; Alzheimer and cancer. However, one of the limiting factors for its application is its unfavorable pharmacokinetic profile. In this work, we propose the coupling of Angiotensin-(1-7) to PAMAM dendrimers in order to evaluate the capacity of the nanocarrier to improve isolated peptide features and to gain insight into the structural as well as the energetic basis of its molecular binding. The In Silico tests were performed in acidic and neutral pH conditions as well as amino-terminated and hydroxyl-terminated PAMAM dendrimers. High-rigor computational approaches, such as molecular dynamics and metadynamics simulations were used. We found that, at neutral pH, PAMAM dendrimers with both terminal types are able to interact stably with 3 Angiotensin-(1-7) peptides through ASP1, TYR4 and PRO7 critical amino acids, however, there are some differences in the binding sites of the peptides. In general, they bind on the surface in the case of the hydroxyl-terminated compact dendrimer and in the internal zone in the case of the amino-terminated open dendrimer. At acidic pH, PAMAM dendrimers with both terminal groups are still able to interact with peptides either internalized or in its periphery, however, the number of contacts, the percentage of coverage and the number of HBs are lesser than at neutral pH, suggesting a state for peptide release. In summary, amino-terminated PAMAM dendrimer showed slightly better features to bind, load and protect Angiotensin-(1-7) peptides.
- Using a reverse genetics system to generate recombinant SARS-CoV-2 expressing robust levels of reporter genes -
Reporter-expressing recombinant virus represents an excellent option and a powerful tool to investigate, among others, viral infection, pathogenicity, and transmission, as well as to identify therapeutic compounds that inhibit viral infection and prophylactic vaccines. To combat the still ongoing coronavirus disease 2019 (COVID-19) pandemic, we have established a robust bacterial artificial chromosome (BAC)-based reverse genetics (RG) system to rapidly generate recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) to study the contribution of viral proteins in viral pathogenesis. In addition, we have also engineered reporter-expressing recombinant viruses in which we place the reporter genes upstream of the viral nucleocapsid (N) gene to promote high levels of reporter gene expression that facilitates the study of SARS-CoV-2 in vitro and in vivo. Although successful, the genetic manipulation of the BAC containing the entire SARS-CoV-2 genome of ~30,000 nucleotides, is challenging. Herein, we depict the technical details to engineer rSARS-CoV-2 expressing reporter genes using the BAC-based RG approach. We describe i) assembly of the full- length (FL) SARS-CoV-2 genome sequences into the empty pBeloBAC, ii) verification of the pBeloBAC-FL, iii) cloning of a Venus reporter gene into the pBeloBAC-FL, and iv) recovery of the Venus-expressing rSARS-CoV-2. By following this protocol, researchers with basic molecular biology and gene engineering techniques knowledge will be able to generate wild-type and reporter-expressing rSARS-CoV-2.
- Reduced Neutralization of SARS-CoV-2 Omicron Variant in Sera from SARS-CoV-1 Survivors after 3-dose of Vaccination -
Recent studies found that Omicron variant escapes vaccine-elicited immunity. Interestingly, potent cross-clade pan- sarbecovirus neutralizing antibodies were found in survivors of the infection by SARS-CoV-1 after BNT162b2 mRNA vaccination (N Engl J Med. 2021 Oct 7;385(15):1401-1406). These pan-sarbecovirus neutralizing antibodies were observed to efficiently neutralize the infection driven by the S protein from both SARS-CoV and multiple SARS-CoV-2 variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) (N Engl J Med. 2021 Oct 7;385(15):1401-1406). However, whether these cross-reactive antibodies could neutralize the Omicron variant is still unknown. Based on the data collected from a cohort of SARS-CoV-1 survivors received 3-dose of immunization, our studies reported herein showed that a high level of neutralizing antibodies against both SARS-CoV-1 and SARS-CoV-2 were elicited by a 3rd-dose of booster vaccination of protein subunit vaccine ZF2001. However, a dramatically reduced neutralization of SARS-CoV-2 Omicron Variant (B.1.1.529) is observed in sera from these SARS-CoV-1 survivors received 3-dose of Vaccination. Our results indicates that the rapid development of pan-variant adapted vaccines is warranted.
- The SARS-CoV-2 spike protein binds and modulates estrogen receptors -
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ER). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ER binding mode. In cultured cells, S DNA transfection increased ER cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS- CoV-2-infected hamsters using [18F]fluoroestradiol (FES) localized lung pathology with increased ER lung levels. Postmortem experiments in lung tissues from SARS-CoV-2-infected hamsters and humans confirmed an increase in cytoplasmic ER expression and its colocalization with S protein in alveolar macrophages. These findings describe the discovery and characterization of a novel S-ER interaction, imply a role for S as an NRC, and are poised to advance knowledge of SARS- CoV-2 biology, COVID-19 pathology, and mechanisms of sex differences in the pathology of infectious disease.
- Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques -
Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.
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 Safety and Efficacy Study of Hymecromone Tablets for the Treatment of Patients With COVID-19. - Condition: COVID-19
Interventions: Drug: Hymecromone tablets; Other: Placebo
Sponsor: Shanghai Zhongshan 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
A Phase Ia, Dose-finding Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults - Condition: COVID-19
Intervention: Biological: Prime-2-CoV_Beta
Sponsors:
University Hospital Tuebingen; FGK Clinical Research GmbH; VisMederi srl; Staburo GmbH; Viedoc Technologies AB
Not yet 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
A Study to Learn About the Study Medicine (Called Nirmatrelvir/Ritonavir) in Pregnant Women With Mild or Moderate COVID-19. - Condition: COVID-19
Interventions: Drug: nirmatrelvir; Drug: ritonavir
Sponsor: Pfizer
Not yet 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
Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia) - Condition: COVID-19
Interventions: Biological: Pfizer-BioNTech Standard dose; Biological: AstraZeneca Standard dose; Biological: Pfizer-BioNTech Fractional dose; Biological: AstraZeneca Fractional dose; Biological: Moderna Standard dose; Biological: Moderna Fractional dose
Sponsors: Murdoch Childrens Research Institute; Universitas Padjadjaran (UNPAD); Universitas Indonesia (UI); Health Development Policy Agency, Ministry of Health Republic of Indonesia; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity
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 750mg; Drug: SSD8432 placebo
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Not yet recruiting
A Study to Evaluate the Efficacy and Safety of DXP604 in Patients With Mild to Moderate COVID-19 - Condition: COVID-19
Intervention: Biological: DXP604
Sponsor:
Wuhan Institute of Biological Products Co., Ltd
Not yet recruiting
Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Clinical Study - Condition: COVID-19
Interventions: Drug: SSD8432 300mg; Drug: SSD8432 750mg; Drug: SSD8432Placebo
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Not yet recruiting
Efficacy of oleandrin and PBI-05204 against bovine viruses of importance to commercial cattle health - CONCLUSIONS: The research demonstrates the potency of oleandrin and PBI-05204 to inhibit infectivity of three important enveloped bovine viruses in vitro. These data showing non-toxic concentrations of oleandrin inhibiting infectivity of three bovine viruses support further investigation of in vivo antiviral efficacy.
SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to downregulate MHC-I surface expression - Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small protein β (2) -microglobulin (β (2) m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those…
A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient - The syndrome of pulmonary SARS-Cov-2 resulted in significant morbidity and mortality, with new variants spreading rapidly. Vaccines to prevent COVID-19 have been developed to minimize the impact and severity; however, adverse effects of the vaccine have been documented in several studies. In our case, we report a case of a young female who presented to the emergency department with fever, dizziness, headache, vomiting, blurring of vision, numbness, and weakness of left upper and lower limbs….
Neutralizing antibody and T cell responses against SARS-CoV-2 variants of concern following ChAdOx-1 or BNT162b2 boosting in the elderly previously immunized with CoronaVac vaccine - CONCLUSION: Boosting with either ChAdOx-1 or BNT162b2 in CoronaVac-primed healthy elderly individuals induced high NAb production against all examined VOCs except Omicron. BNT162b2 stimulated higher NAb and some T-cell responses than ChAdOx-1. Vaccine boosting is, therefore, recommended for elderly individuals previously immunized with CoronaVac.
Red blood cell distribution width as a marker of hyperinflammation and mortality in COVID-19 - CONCLUSIONS: RDW predicts COVID-19-associated ARDS mortality and reflects the hyperinflammatory background and the effects of cytokines such as IL-6, irrespective of tocilizumab treatment.
Antiviral Activity of Medicinal Plants against Human Coronavirus: a systematic scoping review of and experimentations - CONCLUSION: This review shows that complementary medicine have the potential for new drug discovery against coronavirus. Further research is needed before definitive conclusions can be made concerning the safety and efficacy of the use of these medicinal plants.
Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents - Cyclophilin A (CypA) is linked to diverse human diseases including viral infections. With the worldwide emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2), drug repurposing has been highlighted as a strategy with the potential to speed up antiviral development. Because CypA acts as a proviral component in hepatitis C virus, coronavirus and HIV, its inhibitors have been suggested as potential treatments for these infections. Here, we review the structure of cyclosporin A and…
Pyronaridine Protects against SARS-CoV-2 Infection in Mouse - There are currently relatively few small-molecule antiviral drugs that are either approved or emergency-approved for use against severe acute respiratory coronavirus 2 (SARS-CoV-2). One of these is remdesivir, which was originally repurposed from its use against Ebola. We evaluated three molecules we had previously identified computationally with antiviral activity against Ebola and Marburg and identified pyronaridine, which inhibited the SARS-CoV-2 replication in A549-ACE2 cells. The in vivo…
Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism - Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. Since spermidine increases autophagy, we asked if treatment with chloroquine, an inhibitor of autophagy, would shorten the lifespan of mice. Recently, chloroquine has intensively been discussed as a treatment option for COVID-19 patients. To rule out unfavorable long-term effects on longevity, we examined the effect of chronic treatment with chloroquine given…
Gelatin Stabilizes Nebulized Proteins in Pulmonary Drug Delivery against COVID-19 - Delivering medication to the lungs via nebulization of pharmaceuticals is a noninvasive and efficient therapy route, particularly for respiratory diseases. The recent worldwide severe acute respiratory syndrome coronavirus type 2 (SARS- CoV-2) pandemic urges the development of such therapies as an effective alternative to vaccines. The main difficulties in using inhalation therapy are the development of effective medicine and methods to stabilize the biological molecules and transfer them to the…
A novel property of hexokinase inhibition by Favipiravir and proposed advantages over Molnupiravir and 2 Deoxy D glucose in treating COVID-19 - CONCLUSION: Favipiravir could continue to be part of the COVID-19 treatment regimen due to its resistance to host esterases, hexokinase inhibition potential and proven safety through human trials.
Thiazole-based SARS-CoV-2 protease (COV Mpro ) inhibitors: Design, synthesis, enzyme inhibition, and molecular modeling simulations - As an attempt to contribute to the efforts of combating the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for COVID-19, new analogs of the repurposed drug nitazoxanide which showed promising inhibitory efficacy on a viral protease enzyme were designed, synthesized and evaluated for their inhibitory activity on the main protease of the SARS-CoV-2 virus, using the COV2-3CL protease inhibition assay. The obtained results showed that the…
Anti-SARS-CoV-2 activity of various PET-bottled Japanese green teas and tea compounds in vitro - The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) is a serious threat to global public health. The emergence of SARS-CoV-2 variants is a significant concern regarding the continued effectiveness of vaccines and antiviral therapeutics. Thus, natural products such as foods, drinks, and other compounds should be investigated for their potential to treat COVID-19. Here, we examined the in vitro antiviral activity against…
Highly polymerized proanthocyanidins (PAC) components from blueberry leaf and stem significantly inhibit SARS-CoV-2 infection via inhibition of ACE2 and viral 3CLpro enzymes - With the current worldwide pandemic of COVID-19, there is an urgent need to develop effective treatment and prevention methods against SARS-CoV-2 infection. We have previously reported that the proanthocyanidin (PAC) fraction in blueberry (BB) leaves has strong antiviral activity against hepatitis C virus (HCV) and human T-lymphocytic leukemia virus type 1 (HTLV-1). In this study, we used Kunisato 35 Gou (K35) derived from the rabbit eye blueberry (Vaccinium virgatum Aiton), which has a high PAC…
Copper(II) Schiff base complex derived from salen ligand: structural investigation, Hirshfeld surface analysis, anticancer and anti-SARS-CoV-2 - This work deals with the synthesis and characterization of copper(II) complex Cu(salen)(H(2)O) of salen-type Schiff base ligand derived from the condensation of 5-bromo-2-hydroxy-3-methoxybenzaldehyde and ethylenediamine in EtOH. This complex was characterized by different spectroscopic and physicochemical methods. Single crystal X-ray crystallography study revealed that Cu(II) in complex (1) is five-coordinate and adopts a distorted square pyramidal geometry. A DFT calculation was employed…