- Educational Technology in Higher Education on Pandemic Covid-19 Experiences -
The educational technology is very important in the world of education because it can facilitate the process of learning activities both in the classroom and learning activities at home as it is now when learning online or online because of the covid-19 pandemic that spreads throughout the world, including in Indonesia. of learning and learning, the history of the development of educational technology and knowing the meaning of educational technology. The research method used is sourced from secondary data. Secondary data is data obtained from information or knowledge obtained indirectly, among others, includes official documents, books, and research results in the form of reports. The results of this study explain that educational technology has developed steadily where each stage in its development creates a new discovery that facilitates learning activities. The emergence of educational technology makes it easier for educators and students to learn independently and can create the latest innovations in the world of education so that a learning and learning innovation will emerge that makes educators and students able to learn easily and fun.
- SARS-CoV-2 spike conformation determines plasma neutralizing activity -
Numerous safe and effective COVID-19 vaccines have been developed that utilize various delivery technologies and engineering strategies. The influence of the SARS-CoV-2 spike (S) glycoprotein conformation on antibody responses induced by vaccination or infection in humans remains unknown. To address this question, we compared plasma antibodies elicited by six globally-distributed vaccines or infection and observed markedly higher binding titers for vaccines encoding a prefusion-stabilized S relative to other groups. Prefusion S binding titers positively correlated with plasma neutralizing activity, indicating that physical stabilization of the prefusion conformation enhances protection against SARS-CoV-2. We show that almost all plasma neutralizing activity is directed to prefusion S, in particular the S1 subunit, and that variant cross-neutralization is mediated solely by RBD-specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants and longer durability than current technologies.
- Human genetic variants associated with COVID-19 severity are enriched in immune and epithelium regulatory networks -
Human genetic variants can influence the severity of infection with SARS-COV-2. Several genome-wide association studies (GWAS) have been conducted to identify human risk loci that may be involved with COVID-19 severity. However, candidate genes were investigated in the genomic proximity of each locus without considering their functional cellular contexts. Here, we compiled regulatory networks of 77 human contexts to interpret these risk loci by revealing their relevant contexts and associated transcript factors (TF), regulatory elements (REs), and target genes (TGs). 21 human contexts were identified to be associated with COVID-19 severity and grouped into two categories: immune cells and epithelium cells. We further investigated the risk loci in regulatory network of immune cells, epithelium cells and their crosstalk. Two genomic clusters, chemokine receptors cluster and OAS cluster showed the strongest association with COVID-19 severity in the context specific regulatory networks.
- The P3 O-Tert-Butyl-Threonine is Key to High Cellular and Antiviral Potency for Aldehyde-Based SARS-CoV-2 Main Protease Inhibitors -
As an essential enzyme to SARS-CoV-2, main protease (MPro) is a viable target to develop antivirals for the treatment of COVID-19. By varying chemical compositions at both P2 and P3 sites and the N-terminal protection group, we synthesized a series of MPro inhibitors that contain -(S-2-oxopyrrolidin-3-yl)-alaninal at the P1 site. These inhibitors have a large variation of determined IC50 values that range from 4.8 to 650 nM. The determined IC50 values reveal that relatively small side chains at both P2 and P3 sites are favorable for achieving high in vitro MPro inhibition potency, the P3 site is tolerable toward unnatural amino acids with two alkyl substituents on the -carbon, and the inhibition potency is sensitive toward the N-terminal protection group. X-ray crystal structures of MPro bound with 16 inhibitors were determined. All structures show similar binding patterns of inhibitors at the MPro active site. A covalent interaction between the active site cysteine and a bound inhibitor was observed in all structures. In MPro, large structural variations were observed on residues N142 and Q189. All inhibitors were also characterized on their inhibition of MPro in 293T cells, which revealed their in cellulo potency that is drastically different from their in vitro enzyme inhibition potency. Inhibitors that showed high in cellulo potency all contain O-tert-butyl-threonine at the P3 site. Based on the current and a previous study, we conclude that O-tert-butyl-threonine at the P3 site is a key component to achieve high cellular and antiviral potency for peptidyl aldehyde inhibitors of MPro. This finding will be critical to the development of novel antivirals to address the current global emergency of concerning the COVID-19 pandemic.
- SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion -
The newly reported Omicron variant is poised to replace Delta as the most rapidly spread SARS-CoV-2 variant across the world. Cryo-EM structural analysis of the Omicron variant spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 and R498 in the RBD with ACE2. These interactions appear to compensate for other Omicron mutations such as K417N known to reduce ACE2 binding affinity, explaining our finding of similar biochemical ACE2 binding affinities for Delta and Omicron variants. Neutralization assays show that pseudoviruses displaying the Omicron spike protein exhibit increased antibody evasion, with greater evasion observed in sera obtained from unvaccinated convalescent patients as compared to doubly vaccinated individuals (8- vs 3-fold). The retention of strong interactions at the ACE2 interface and the increase in antibody evasion are molecular factors that likely contribute to the increased transmissibility of the Omicron variant.
- Arsenal of Nanobodies for Broad-Spectrum Countermeasures against Current and Future SARS-CoV-2 Variants of Concerns -
Nanobodies offer several potential advantages over mAbs for the control of SARS-CoV-2. Their ability to access cryptic epitopes conserved across SARS-CoV-2 variants of concern (VoCs) and feasibility to engineer modular, multimeric designs, make these antibody fragments ideal candidates for developing broad-spectrum therapeutics against current and continually emerging SARS-CoV-2 VoCs. Here we describe a diverse collection of 37 anti-SARS-CoV-2 spike glycoprotein nanobodies extensively characterized as both monovalent and IgG Fc-fused bivalent modalities. The panel of nanobodies were shown to have high intrinsic affinity; high thermal, thermodynamic and aerosolization stability; broad subunit/domain specificity and cross-reactivity across many VoCs; wide-ranging epitopic and mechanistic diversity; high and broad in vitro neutralization potencies; and high neutralization efficacies in hamster models of SARS-CoV-2 infection, reducing viral burden by up to six orders of magnitude to below detectable levels. In vivo protection was demonstrated with anti-RBD and previously unreported anti-NTD and anti-S2 nanobodies. This collection of nanobodies provides a therapeutic toolbox from which various cocktails or multi-paratopic formats could be built to tackle current and future SARS-CoV-2 variants and SARS-related viruses. Furthermore, the high aerosol-ability of nanobodies provides the option for effective needle-free delivery through inhalation.
- A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors -
Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of- signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for high-throughput screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified four molecules, including the broad-spectrum antiviral merimepodib/VX-497, which show anti-nsp5 activity and inhibit SARS-CoV-2 replication in A549-ACE2 cells with IC50 values in the 4-21 micromolar range. The here described assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.
- APOBEC-mediated Editing of SARS-CoV-2 Genomic RNA Impacts Viral Replication and Fitness -
During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more virulent and evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Recent SARS- CoV-2 sequence analyses showed a strong bias toward C-to-U mutation, suggesting that host APOBEC cytosine deaminases with immune functions may cause the mutation. We report the experimental evidence demonstrating that APOBEC3A and APOBEC1 can efficiently edit SARS-CoV-2 RNA to produce C-to-U mutation at specific sites. However, APOBEC-editing does not inhibit the viral RNA accumulation in cells. Instead, APOBEC3A-editing of SARS-CoV-2 promotes viral replication/propagation, suggesting that SARS-CoV-2 utilizes the APOBEC-mediated mutations for fitness and evolution. Unlike the unpredictability of random mutations, this study has significant implications in predicting the potential mutations based on the UC/AC motifs and surrounding RNA structures, thus offering a basis for guiding future antiviral therapies and vaccines against the escape mutants.
- US Parents’ Domestic Labor Over the Course of the COVID-19 Pandemic -
• Objective: This study assesses changes in parents’ divisions of housework and childcare over the course of the COVID-19 pandemic. • Background: Assessing the long-term consequences of the COVID-19 pandemic for gender equality requires understanding how and why labor arrangements shifted as the pandemic progressed. Yet, we know little about US parents’ domestic arrangements beyond the early days of the COVID-19 pandemic or how simultaneous changes in men’s and women’s employment, earnings, telework, gender ideologies, and access to care supports may have altered domestic labor arrangements. • Method: This study assesses change in parents’ domestic labor using fixed-effects regression on data from a longitudinal panel of 700 different-sex partnered US parents collected at three time points: March 2020, April 2020, and November 2020. • Results: Partnered parents’ divisions of housework and childcare became more equal in the early days of the pandemic, but reverted toward pre-pandemic levels by the fall of 2020. Changes in parents’ divisions of domestic labor were largely driven by changes in parents’ labor force conditions, and especially by fathers’ labor force conditions. Decreases in fathers’ labor force participation and increases in telecommuting in April portended increases in partnered fathers’ shares of domestic tasks. As fathers increased time in paid work and returned to in- person work by fall, their shares of domestic labor fell. • Conclusion: Overall, results suggest that promoting full- time employment among mothers and greater time at home for fathers are key in facilitating a more equal division of domestic labor within families post-pandemic.
- Group processes and interoperability: A longitudinal case study analysis of the UK’s civil contingency response to Covid-19 -
Our case study explored a Local Resilience Forum’s (LRF) civil contingency response to COVID-19 in the UK. We undertook 19 semi-structured ethnographic longitudinal interviews, between 25th March 2020 and 17th February 2021, with a Director of a Civil Contingencies Unit and a Chief Fire Officer who both played key roles within their LRF. Within these interviews, we focused on their strategic level decision-making and how their relationship with national government impacted on local processes and outcomes. Using a form of grounded theory, our data describes the chronological evolution of an increasingly effective localised approach toward outbreak control and a growing resilience in dealing with concurrent emergency incidents. However, we also highlight how national government organisations imposed central control on aspects of the response in ways that undermined or misaligned with local preparedness. Thus, during emergencies central governments can undermine the principle of subsidiarity and damage the ways in which LRFs can help scaffold local resilience. Our work contributes to the theoretical understanding of the social psychological factors that can shape the behaviour of responder agencies during a prolonged crisis. In particular, the implications of our analysis for advancing our conceptual understanding of strategic decision-making during emergencies are discussed.
- Four points regarding reproducibility and external statistical validity: a comment on Walter et al. -
Walter et al. (2021) present phase 1–2–3 trial data that show two doses of the BNT162b2 (Pfizer–BioN-Tech) Covid-19 vaccine were safe and effective in children aged 5–11 years. Given that millions of children in this age group are receiving the paediatric Pfizer COVID-19 vaccine, that there are potential risks, and that the balance of benefits over potential risks is more limited in children compared to adults due to low rates of serious disease (ATAGI 2021), gold standards ought to be applied to supporting data in terms of placebo-controlled disease endpoint efficacy trials, safety databases large enough to detect adverse events, and appropriate data sharing to enable reproduction and scrutiny of results. Four points are worthy of attention regarding the reproducibility and external statistical validity of the analysis reported in Walter et al. (2021). ‘External validity’ refers to the extent to which conclusions drawn from the data (and statistical tests thereof) are likely to correspond to, or be generalisable to, the real world (Campbell 1957). ‘Reproducibility’ refers to the ability of independent researchers to draw the same conclusions from the data (Kass et al. 2016).
- The rise and fall of SARS-CoV-2 variants and the mutational profile of Omicron -
In late December of 2019, high throughput sequencing technologies enabled rapid identification of SARS-CoV-2 as the etiological agent of COVID-19, and global sequencing efforts are now a critical tool for monitoring the ongoing spread and evolution of this virus. Here, we analyze a subset (n=87,032) of all publicly available SARS-CoV-2 genomes (n=~5.6 million) that were randomly selected, but equally distributed over the course of the pandemic. We plot the appearance of new variants of concern (VOCs) over time and show that the mutation rates in Omicron viruses are significantly greater than those in previously identified SARS-CoV-2 variants. Mutations in Omicron are primarily restricted to the spike protein, while 25 other viral proteins–including those involved in SARS-CoV-2 replication–are highly conserved. Collectively, this suggests that the genetic distinction of Omicron primarily arose from selective pressures on the spike, and that the fidelity of replication of this variant has not been altered.
- ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection -
Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchioalveolar lavage fluid from critically ill COVID-19 patients was associated with reduced ICU and hospitalization times. We found ACE2+ exosomes were induced by SARS- CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection.
- Evidence for a Potential Pre-Pandemic SARS-like Coronavirus Among Animals in North America -
In late 2019, a novel coronavirus began circulating within humans in central China. It was designated SARS-CoV-2 because of its genetic similarities to the 2003 SARS coronavirus (SARS-CoV). Now that SARS-CoV-2 has spread worldwide, there is a risk of it establishing new animal reservoirs and recombination with native circulating coronaviruses. To screen local animal populations in the United States for exposure to SARS-like coronaviruses, we developed a serological assay using the receptor binding domain (RBD) from SARS-CoV-2. SARS-CoV-2’s RBD differs from common human and animal coronaviruses allowing us to identify animals previously infected with SARS-CoV or SARS-CoV-2. Using an indirect ELISA for SARS-CoV-2’s RBD, we screened serum from wild and domestic animals for the presence of antibodies against SARS- CoV-2’s RBD. Surprisingly pre-pandemic feline serum samples submitted to the University of Tennessee Veterinary Hospital were ~70% positive for anti-SARS RBD antibodies. This was independent of prior infection with a feline coronavirus (FCoV), eliminating the possibility of FCoV cross-reactivity. We also identified several white-tailed deer from South Carolina that were also positive for anti-SARS-CoV-2 antibodies. These results bring up an intriguing possibility of a circulating agent (likely a coronavirus) with enough similarity to the SARS RBD to generate cross-reactive antibodies. Finding seropositive cats and white-tailed deer prior to the current SARS-CoV-2 pandemic, further highlights our lack of information about circulating coronaviruses in other species.
- A Computational Dissection of Spike protein of SARS-CoV-2 Omicron Variant -
The emergence of SARS-CoV-2 omicron variant in late November, 2021 and its rapid spread to different countries, warns the health authorities to take initiative to work on containing its spread. The omicron SARS-CoV-2 variant is unusual from the other variants of concerns reported earlier as it harbors many novel mutations in its genome particularly with >30 mutations in the spike glycoprotein alone. The current study investigated the variation in binding mechanism which it carries compared to the wild type. The study also explored the interaction profile of spike- omicron with human ACE2 receptor. The structure of omicron spike glycoprotein was determined though homology modeling. The interaction analysis was performed through docking using HADDOCK followed by binding affinity calculation. Finally, the comparison of interactions were performed among spike-ACE2 complex of wild type, delta and omicron variants. The interaction analysis has revealed the involvement of highly charged and polar residues (H505, Arg498, Ser446, Arg493, and Tyr501) in the interactions. The important novel interactions in the spike-ACE2-omicron complex was observed as S494:H34, S496:D38, R498:Y41, Y501:K353, and H505:R393 and R493:D38. Moreover, the binding affinity of spike- ACE2-omicron complex (-17.6Kcal/mol) is much higher than wild type-ACE2 (-13.2Kcal/mol) and delta-ACE2 complex (-13.3Kcal/mol). These results indicate that the involvement of polar and charged residues in the interactions with ACE2 may have an impact on increased transmissibility of omicron variant.
Trial to Evaluate Nitazoxanide for Treatment of Mild COVID-19 in Subjects Not at High Risk of Severe Illness - Condition: COVID-19
Interventions: Drug: Nitazoxanide; Drug: Placebo; Dietary Supplement: Vitamin Super-B Complex
Sponsor: Romark Laboratories L.C.
Not yet recruiting
Trial to Evaluate Nitazoxanide for Treatment of Mild or Moderate COVID-19 in Subjects at High Risk of Severe Illness - Condition: COVID-19
Interventions: Drug: Nitazoxanide; Dietary Supplement: Vitamin Super-B Complex; Drug: Placebo; Other: Standard of Care
Sponsor:
Romark Laboratories L.C.
Not yet recruiting
A Double-blind Randomized Controlled Trial of Ivermectin With Favipiravir in Mild-to-moderate COVID-19 Patients - Condition: COVID-19
Interventions: Drug: Ivermectin Tablets; Other: Placebo
Sponsors: Mahidol University; Prince of Songkla University
Not yet recruiting
Australian Phase 2/3b Study to Assess Effectiveness of a Protein-based Covid-19 Vaccine (Spikogen) - Condition: COVID-19
Intervention: Biological: Spikogen/Covax-19
Sponsors:
Vaxine Pty Ltd; Australian Respiratory and Sleep Medicine Institute; Cinnagen
Not yet recruiting
Study of GRT-R910 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Boost Vaccine in Healthy Volunteers - Condition: COVID-19
Interventions: Biological: GRT-R910 booster 113 days after prime; Biological: GRT-R910 booster 28 days after prime
Sponsor: Gritstone Oncology, Inc.
Recruiting
A Safety, Tolerability, and Efficacy Study of IBI314 in Ambulatory Patients With COVID-19 - Condition: COVID-19
Interventions: Biological: IBI314; Other: Placebo
Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Not yet recruiting
Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial - Condition: COVID-19
Interventions: Biological: Adrecizumab (HAM 8101); Drug: Placebo
Sponsor: Universitätsklinikum Hamburg-Eppendorf
Not yet recruiting
Safety, Tolerability, and Treatment Effect of Belnacasan in Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: Belnacasan; Drug: Placebo
Sponsor:
MedStar Health
Recruiting
A Study Evaluating Tocilizumab in Pediatric Patients Hospitalized With COVID-19 - Condition: COVID-19
Intervention: Drug: Tocilizumab
Sponsor: Hoffmann- La Roche
Not yet recruiting
Immunogenicity Study of the Covid-19 (Recombinante) Vaccine With a 4 or 8 Week Interval Between the First Doses. - Condition: COVID-19
Intervention: Biological: Covid-19 (recombinante) vaccine
Sponsor: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
Active, not recruiting
A Study to Evaluate Efficacy and Safety of the Combination of SCTA01 & SCTA01C in Outpatients With COVID-19 - Condition: COVID-19
Interventions: Drug: SCTA01 and SCTA01C; Drug: Placebo
Sponsor: Sinocelltech Ltd.
Not yet recruiting
Efficacy,Immunogenicity and Safety of COVID-19 Vaccine , Inactivated Booster Dose in Adults Aged 18 Years and Above - Condition: COVID-19
Interventions: Biological: Medium-dosage COVID-19 Vaccine,Inactivated; Biological: High-dosage COVID-19 Vaccine,Inactivated; Biological: Placebo-comparator group
Sponsor:
Sinovac Research and Development Co., Ltd.
Not yet recruiting
Communities Fighting COVID-19! - Condition: Covid19
Interventions: Other: COVID-19 Testing Home-based (Aim 1); Other: COVID-19 Testing Mobile (Aim 1); Other: COVID-19 Testing Mobile Approach 1 (Aim 2); Other: COVID-19 Testing Mobile Approach 2 (Aim 2)
Sponsors: San Diego State University; National Cancer Institute (NCI)
Recruiting
Clinical Trial for Oral Formula of Vanillin and Wheat Germ Oil for Treatment of Mild and Moderate COVID-19 Viral Disease - Condition: Mild-to-moderate COVID-19
Intervention: Drug: Oral Capsule
Sponsors:
Alexandria University; Assoc. Prof. Ayman Baeis; Dr. Noha Alaa Eldine Hassan Hamdy; Ph. Hanya Hesham Sweilam
Recruiting
Combination Assessment Trial of COVID-19 Vaccines (COMBAT-COVID) - Condition: COVID 19 Vaccine
Interventions: Biological: BIBP (CNBG, Sinopharm) WIV; Biological: CanSinoBIO; Biological: AstraZeneca ChAdOx
Sponsors:
Aga Khan University Hospital, Pakistan; Coalition for Epidemic Preparedness Innovations; University of Oxford; International Vaccine Institute; Harvard Medical School (HMS and HSDM); Chughtai Lab; National Institute of Health, Pakistan
Not yet recruiting
Coronavirus disease 2019-induced hypercoagulability and its clinical implications - Coronavirus disease 2019 is the disease produced by severe acute respiratory syndrome-coronavirus-2, which is introduced into the host’s cell thanks to the angiotensin-converting enzyme 2 receptor. Once there, it uses the cell’s machinery to multiply itself. In this process, it generates an immune response that stimulates the lymphocytes to produce cytokines and reactive oxygen species that begin to deteriorate the endothelial cell. Complement activation, through the complement attack complex…
Effects of simeprevir on the replication of SARS-CoV-2 in vitro and in transgenic hACE2 mice - In a bid to contain the current COVID-19 (coronavirus disease 2019) pandemic, various countermeasures have been applied. To date, however, there is a lack of an effective drug for the treatment of COVID-19. Through molecular modelling studies, simeprevir, a protease inhibitor approved for the management of hepatitis C virus infection, has been predicted as a potential antiviral against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causative agent of COVID-19. Here we assessed…
The binding of heparin to spike glycoprotein inhibits SARS-CoV-2 infection by three mechanisms - Heparin, a naturally occurring glycosaminoglycan, has been found to have antiviral activity against SARS-CoV-2, the causative virus of COVID-19. To elucidate the mechanistic basis for the antiviral activity of heparin, we investigated the binding of heparin to the SARS-CoV-2 spike glycoprotein by means of sliding window docking, molecular dynamics simulations, and biochemical assays. Our simulations show that heparin binds at long, positively-charged patches on the spike glycoprotein, thereby…
SARS-CoV-2 receptor binding domain fusion protein efficiently neutralizes virus infection - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Currently, as dangerous mutations emerge, there is an increased demand for specific treatments for SARS-CoV-2 infected patients. The spike glycoprotein on the virus membrane binds to the angiotensin converting enzyme 2) ACE2 (receptor on host cells through its receptor binding domain (RBD) to mediate virus entry. Thus, blocking this interaction may inhibit viral entry and consequently stop…
Early use of canakinumab to prevent mechanical ventilation in select COVID-19 patients: A retrospective, observational analysis - CONCLUSION: The use of canakinumab (300 mg, s.c.) in the early stage of COVID-19 with mild-to-moderate respiratory failure was superior to SOC at preventing clinical deterioration and may warrant further investigation as a treatment option for patients with COVID-19 who experience a hyperinflammatory response in the early stage of the disease.
Elucidation of SARS-Cov-2 Budding Mechanisms through Molecular Dynamics Simulations of M and E Protein Complexes - SARS-CoV-2 and other coronaviruses pose major threats to global health, yet computational efforts to understand them have largely overlooked the process of budding, a key part of the coronavirus life cycle. When expressed together, coronavirus M and E proteins are sufficient to facilitate budding into the ER-Golgi intermediate compartment (ERGIC). To help elucidate budding, we ran atomistic molecular dynamics (MD) simulations using the Feig laboratory’s refined structural models of the…
Targeting genomic SARS-CoV-2 RNA with siRNAs allows efficient inhibition of viral replication and spread - A promising approach to tackle the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) could be small interfering (si)RNAs. So far it is unclear, which viral replication steps can be efficiently inhibited with siRNAs. Here, we report that siRNAs can target genomic RNA (gRNA) of SARS-CoV-2 after cell entry, and thereby terminate replication before start of transcription and prevent virus-induced cell death. Coronaviruses replicate via negative sense RNA intermediates using a unique…
Exploring the therapeutic nature of limonoids and triterpenoids against SARS-CoV-2 by targeting nsp13, nsp14, and nsp15 through molecular docking and dynamic simulations - BACKGROUND AND AIM: The ongoing global pandemic due to SARS-CoV-2 caused a medical emergency. Since December 2019, the COVID-19 disease is spread across the globe through physical contact and respiratory droplets. Coronavirus caused a severe effect on the human immune system where some of the non-structural proteins (nsp) are involved in virus-mediated immune response and pathogenesis. To suppress the viral RNA replication mechanism and immune-mediated responses, we aimed to identify limonoids…
2-Phenoxyacetamide Derivatives as SARS-CoV-2 Main Protease Inhibitor: In Silico Studies - 2-Phenoxyacetamide group has been identified as one of markers in the discovery and development of SARS-CoV-2 antiviral agent through its main protease (M^(pro)) inhibition pathway. This study aims to study a series of 2-phenoxyacetamide derivatives using in silico method toward SARS-CoV-2 M^(pro) as the protein target. The study was initiated by employing structure-based pharmacophore to virtually screen and to select the ligands, which have the best fit score (hits) along with the common…
Viruses, Vaccines, and COVID-19: Explaining and Improving Risky Decision-making - Risky decision-making lies at the center of the COVID-19 pandemic and will determine future viral outbreaks. Therefore, a critical evaluation of major explanations of such decision-making is of acute practical importance. We review the underlying mechanisms and predictions offered by expectancy-value and dual-process theories. We then highlight how fuzzy-trace theory builds on these approaches and provides further insight into how knowledge, emotions, values, and metacognitive inhibition…
Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System - Mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made this virus more infectious. Previous studies have confirmed that non-structural protein 13 (NSP13) plays an important role in immune evasion by physically interacting with TANK binding kinase 1 (TBK1) to inhibit IFNβ production. Mutations have been reported in NSP13; hence, in the current study, biophysical and structural modeling methodologies were adapted to dissect the influence of major mutations in NSP13,…
Network Pharmacology and Experimental Assessment to Explore the Pharmacological Mechanism of Qimai Feiluoping Decoction Against Pulmonary Fibrosis - Pulmonary fibrosis (PF) is one of the pathologic changes in COVID-19 patients in convalescence, and it is also a potential long-term sequela in severe COVID-19 patients. Qimai Feiluoping decoction (QM) is a traditional Chinese medicine formula recommended in the Chinese national medical program for COVID-19 convalescent patients, and PF is one of its indications. Through clinical observation, QM was found to improve the clinical symptoms and pulmonary function and reduce the degree of PF of…
In-Silico Design of a Novel Tridecapeptide Targeting Spike Protein of SARS-CoV-2 Variants of Concern - Several mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased the transmission and mortality rate of coronavirus disease-19 (COVID-19) across the globe. Although many vaccines have been developed, a large proportion of the global population remains at high risk of infection. The current study aims to develop an antiviral peptide capable of inhibiting the interaction of SARS-CoV-2 spike protein and its six major variants with the host cell angiotensin-converting…
Systemic corticosteroids for management of COVID-19: Saving lives or causing harm? - The underlying cause of many complications associated with severe COVID-19 is attributed to the inflammatory cytokine storm that leads to acute respiratory distress syndrome (ARDS), which appears to be the leading cause of death in COVID-19. Systemic corticosteroids have anti-inflammatory activity through repression of pro-inflammatory genes and inhibition of inflammatory cytokines, which makes them a potential medical intervention to diminish the upregulated inflammatory response. Early in the…
Recovery of SARS-CoV-2 from large volumes of raw wastewater is enhanced with the inuvai R180 system - Wastewater-based epidemiology (WBE) for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a powerful tool to complement syndromic surveillance. Although detection of SARS-CoV-2 in raw wastewater may be prompted with good recoveries during periods of high community prevalence, in the early stages of population outbreaks concentration procedures are required to overcome low viral concentrations. Several methods have become available for the recovery of SARS-CoV-2 from raw wastewater,…
E6以及人肺腺癌细胞Calu‑3，检测肌醇六磷酸酯钠水合物的抗SARS‑CoV‑2活性。实验结果显示，肌醇六磷酸酯钠水合物能有效抑制SARS‑CoV‑2对上述易感细胞的感染，且细胞毒性较小，有希望作为有效抗SARS‑CoV‑2感染的药物，具有应用前景。 - link
A DOORBELL SYSTEM FOR MONITORING AND RECORDING A PHYSIOLOGICAL DATA OF A PERSON - AbstractTitle: A doorbell system for monitoring and recording a physiological data of a person The present invention provides a doorbell system 500 for monitoring and recording a physiological data of a person. The doorbell system 500 having a transmitter module 100 and a receiving module 200. The transmitter module 100 is having a TOF sensor module 110, an ultrasound detector 120, and an infrared detector 130. Further, a speech recognition system 150, a facial recognition system 160, and a temperature detector 190 are provided for recognizing speech, face, and temperature of the person by comparing pre-stored data. A controlling module 180 is set with a predefined commands for communicating with the transmitter module 100 and receiving module 200. The collected facial and speech data is compared and matched with the pre-stored data then the temperature detector 190 triggers and the door opens when the captured body temperature of the person is matched within the predefined range of temperature.Figure 1 - link
A study of contemporary trends in investing patterns, household savings, and economic investment. - Because household savings and household investments are intertwined and interdependent, they are discussed briefly in this paper. Household savings account for more than half of a country’s capital formation, which fluctuates due to a variety of economic factors such as inflation and interest rates. Households should gradually shift their savings and investments from physical assets to financial assets to avoid a sudden change in wealth. They should also save and invest using a variety of platforms. Trends in investing and saving will be easier to track and measure this way. This year’s domestic saving rate in India is 2.3 percent lower than last year’s and 1.2 percent lower than the year before. Since 2011, general domestic savings have been steadily declining, with the trend continuing into the following year. According to official data, the GDP in 2020 shrank by 23.9%, the least in previous years and the least since the Covid-19 pandemic in previous years. As a result, the information presented in this paper is drawn from and evaluated from other sources - link
靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗 - 本发明公开了一种靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗。本申请的第一方面提供一种分离的DNA分子组合，该DNA分子组合包括第一DNA分子和第二DNA分子和第三DNA分子中的至少一种。通过第一DNA分子以及第二DNA分子和/或第三DNA分子的组合，利用第一DNA分子最终合成的mRNA诱导高滴度的交叉中和抗体，利用第二DNA分子和/或第三DNA分子最终合成的mRNA诱导新冠病毒特异性的细胞毒性T淋巴细胞，从而高效地同时激活相对独立的体液免疫应答和细胞免疫应答，应对新冠病毒在流行传播过程中产生的突变毒株所引发的突破性感染。 - link
跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途 - 本发明公开了跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途。本发明通过亲和垂钓及活性导向分离获得3种化合物，证实该类化合物可以直接地与跨膜丝氨酸蛋白酶2结合，KD<13μM，且能够显著抑制跨膜丝氨酸蛋白酶2的催化活性。在细胞水平上可以有效的抑制新型冠状病毒SARS‑CoV‑2假病毒入侵，表明该类化合物对于制备治疗和/或预防病毒感染药物具有非常积极的作用。化合物1 化合物2 化合物3。 - link
PROLIPOSOMAL DRY POWDER INHALER OF REMDESIVIR - The present invention is related to Proliposomal Dry Powder Inhaler of Remdesivir and its method thereof for the treatment of viral infections such Coronaviridae (including COVID-19 infection). - link