- Mask Using Practice among Bangladeshi Population During COVID-19 Pandemic: A Video-Based Observational Study -
Background: Although the government of Bangladesh made the use of masks mandatory in public settings during COVID-19, individuals have been reluctant to follow. We intended to know how many people used face masks in public settings during COVID-19. Methodology: This study was conducted in several public settings in Shahbag, an urban sub- district of Dhaka; and Sirajdikhan, a rural sub-district of Munshiganj in Bangladesh on November 2020. A total of 4011 people were identified from the video-graphic data captured from 20 public places for monitoring the use of masks. Finding: More than two-thirds of those observed had no face masks or did not utilize them properly. People in urban regions (43%) used mask more in an appropriate manner than those in rural areas (26%). Females wore masks comparatively more than males (53% vs. 35%, p-value <0.001). People used masks more in the morning than in the afternoon (39% vs. 34%, p-value <0.001). People were seen to use a mask more in hospital areas (60%) than in other places. However, in public transportation stands only one-fourth (25%) of the people wore a mask in an appropriate manner. In binary logistic regression male sex, rural area, public places and time of observation (afternoon) were found as risk factors for not wearing a mask. Interpretation: The general population of both rural and urban areas of Bangladesh is reluctant to wear face masks. Along with the ongoing vaccination campaign, people of Bangladesh need to wear masks for the prevention of COVID-19. Funding: This research has been partially supported by Bangabandhu Sheikh Mujib Medical University.
- Risk perception, illusory superiority, and personal responsibility during COVID-19: An experimental study of attitudes to staying home -
Individual decision-making about social distancing, self-quarantine and self-isolation is crucial in managing the COVID-19 pandemic. In the rapidly evolving pandemic, little is known about how different government communication strategies may systematically affect people’s attitudes to staying home or going out, nor the extent to which people perceive and process the risk of different scenarios. In this study, we report results from a sample of 581 participants (residing in the United Kingdom), and we examine the degree to which participants’ attitudes regarding the permissibility of leaving one’s home are (1) sensitive to different levels of risk of viral transmission in specific scenarios, (2) sensitive to communication framings that are either imperative or that invite reasoning about scenarios, or (3) creating “loopholes” for themselves when scenarios are framed with reference to the participants themselves rather than in general terms. We find that participants’ attitudes to social distancing are sensitive to the level of risk of transmission, and that when scenarios are framed in imperative terms, rather than when their reasoning is encouraged, participants have more impermissive attitudes to going out in Minimal Risk scenarios, with a trend of decreased permissiveness more generally; for self-loopholes, more research is needed to determine if participants make exceptions for themselves. Thus, subject to the limitations of this study, during phases where it is important to promote self-isolation for all scenarios, including those perceived to be low risk, imperative communication may be best.
- Perceptions and illusions of students regarding presumably undetected cheating during the COVID-19 pandemic in Greece -
The present study constitutes a preliminary research on the attitudes and perceptions of students in Greece concerning cheating in exams and plagiarism in the era of the COVID-19 pandemic. A survey conducted among 578 students shows a sharp increase in the employment of underhanded means by students towards attaining better grades in the exams. These findings need to be evaluated by the academic community to put a check on the rising number of instances of academic fraud.
- Changes in youth mental health, psychological wellbeing, and substance use during the COVID-19 pandemic: A rapid review -
Background: The focus of this review was to assess changes in youth mental health, psychological wellbeing, or substance use, as well as changes or disruptions to the delivery of mental health or substance use services for young people during the COVID-19 pandemic. Method: We conducted a rapid review of the literature on our outcomes of interest among youth (age <=25) in the context of the COVID-19 pandemic. Primary studies and systematic reviews on change were eligible for inclusion. Searches were conducted in PubMed and Embase in May 2021, and two reviewers screened studies for inclusion. We report results using a narrative synthesis. Results: We included 156 primary publications. A variety of methods were used to assess change, including prospective assessment of longitudinal cohorts, retrospective recall by participants in cross-sectional and qualitative studies, and comparison of peri-pandemic data to pre-pandemic normative values. Publications regarding mental health (n = 121) and psychological wellbeing (n = 26) generally indicated poor outcomes during the pandemic period. Publications on substance use (n = 41) revealed overall declines or unchanged patterns of use, though certain groups reported increased or problematic use. Studies of service delivery (n = 11) indicated a generally positive reception for helplines and telehealth, although some youth experienced difficulties accessing mental health services. Conclusions: The evidence indicates negative impacts of the COVID-19 pandemic on young people’s mental health, although declines in alcohol and nicotine use were also found. Services will need to continue to adapt as the pandemic progresses, particularly to support disadvantaged youth who lack access to telehealth resources.
- Adolescents’ Social Environment and Executive Functions Predict Long-term Mental Health and Feelings of Future Uncertainty Throughout the COVID-19 Pandemic -
The COVID-19 pandemic has negatively impacted adolescents’ mental health (i.e. mood and life satisfaction). Some adolescents are at risk to be disproportionally hit by the pandemic due to vulnerabilities in their social environment. In the present longitudinal study, we explored adolescents’ mood trajectories throughout the pandemic, and whether vulnerabilities in the social environment (i.e. household and socioeconomic hardship) predicted adolescents’ mental health directly and indirectly through feelings of uncertainty about the future. We also investigated whether executive functions and age buffered these relationships. In total, 177 Dutch-speaking adolescents aged 10 – 18 years (Mage = 15.64, SDage = 1.72, 80% females at T1) participated in all three waves (T1= May 2020, T2 = November 2020, T3 = May 2021) of an online survey. Mood results demonstrated that feelings of vigor stabilized, after an initial dip between T1 and T2, but that feelings of tension and depression continued to increase throughout the pandemic. Higher exposure to household and socioeconomic hardship predicted negative mood and lower life satisfaction and was mediated by feelings of uncertainty about the future. Irrespective of the exposure to household and socioeconomic hardship, adolescents with better executive functions reported better mood in the aftermath of the pandemic, partially due to lower feelings of future uncertainty. However, no associations were observed with life satisfaction. These novel findings imply that adolescents’ mental health issues may outlast the COVID-19 pandemic. Nonetheless, executive functioning is a protective factor operating via feelings of future uncertainty, which makes them promising mechanistic targets for intervention.
- Predicting self-harm and suicide ideation during the COVID-19 pandemic in Indonesia: A brief report of nationwide survey -
Background: It is estimated that 77.0% of suicide cases occurred in low-and-middle-income countries (LMICs), which would increase because of the COVID-19 pandemic and socioeconomic inequity. However, there is lack of reports on this topic from LMICs, especially during the pandemic. Therefore, this nationwide study aimed to explore self-harm and suicide ideation and its predictive variables during the pandemic in Indonesia as a MIC with the highest COVID-19 fatality rate in Asia. Methods: Non-random sampling online survey was conducted nationwide between 25 May and 16 June
- Spike protein cleavage-activation mediated by the SARS-CoV-2 P681R mutation: a case-study from its first appearance in variant of interest (VOI) A.23.1 identified in Uganda -
The African continent like all other parts of the world with high infection/low vaccination rates can, and will, be a source of novel SARS-CoV-2 variants. The A.23 viral lineage, characterized by three spike mutations F157L, V367F and Q613H, was first identified in COVID-19 cases from a Ugandan prison in July 2020, and then was identified in the general population with additional spike mutations (R102I, L141F, E484K and P681R) to comprise lineage A.23.1 by September 2020, with this virus being designated a variant of interest (VOI) in Africa and with subsequent spread to 26 other countries. The P681R spike substitution of the A.23.1 VOI is of note as it increases the number of basic residues in the sub-optimal SARS-CoV-2 spike protein furin cleavage site; as such, this substitution may affect viral replication, transmissibility or pathogenic properties. The same P681R substitution has also appeared in B.1.617 variants, including B.1.617.2 (Delta). Here, we performed assays using fluorogenic peptides mimicking the S1/S2 sequence from A.23.1 and B.1.617.2 and observed significantly increased cleavability with furin, compared to sequences derived from the original Wuhan-Hu1 S1/S2. We performed functional infectivity assays using pseudotyped MLV particles harboring SARS-CoV-2 spike proteins and observed an increase in transduction for A.23.1-pseudotyped particles compared to Wuhan-Hu-1 in Vero- TMPRSS2 and Calu-3 cells (with a presumed early entry pathway), although lowered infection in Vero E6 cells (with a presumed late entry pathway). However, these changes in infectivity were not reproduced in the original Wuhan-Hu-1 spike bearing only the P681R substitution. Our findings suggest that while A.23.1 has increased furin-mediated cleavage linked to the P681R substitution, which may affect viral infection and transmissibility, this substitution alone is not sufficient and needs to occur on the background of other spike protein changes to enable its full functional consequences.
- The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro) -
The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or Mpro, is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of Mpro were obtained at cryogenic temperature or room temperature only. Here we report a series of high- resolution crystal structures of unliganded Mpro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for Mpro, including a mobile water interleaved between the catalytic dyad, mercurial conformational heterogeneity in a key substrate-binding loop, and a far-reaching intramolecular network bridging the active site and dimer interface. Our results may inspire new strategies for antiviral drug development to counter-punch COVID-19 and combat future coronavirus pandemics.
- SARS-CoV-2 spike-glycoprotein processing at S1/S2 and S2’ and shedding of the ACE2 viral receptor: roles of Furin and TMPRSS2 and implications for viral infectivity and cell-to-cell fusion -
The Spike (S)-protein of SARS-CoV-2 binds host-cell receptor ACE2 and requires proteolytic ‘’priming’’ at PRRAR685{downarrow} into S1 and S2 (cleavage at S1/S2), and ‘’fusion-activation’’ at KPSKR815{downarrow} (cleavage at S2’) for viral entry. In vitro, Furin cleaved peptides mimicking the S1/S2 cleavage site more efficiently than at the putative S2’, whereas TMPRSS2 inefficiently cleaved both sites. In HeLa cells Furin-like enzymes mainly cleaved at S1/S2 during intracellular protein trafficking, and S2’ processing by Furin at KPSKR815{downarrow} was strongly enhanced by ACE2, but not for the optimized S2’ KRRKR815{downarrow} mutant (S2’), whereas individual/double KR815AA mutants were retained in the endoplasmic reticulum. Pharmacological Furin-inhibitors (Boston Pharmaceuticals, BOS-inhibitors) effectively blocked endogenous S-protein processing in HeLa cells. Furthermore, we show using pseudotyped viruses that while entry by a ‘’pH-dependent’’ endocytosis pathway in HEK293 cells did not require Furin processing at S1/S2, a ‘’pH- independent’’ viral entry in lung-derived Calu-3 cells was sensitive to inhibitors of Furin (BOS) and TMPRSS2 (Camostat). Consistently, these inhibitors potently reduce infectious viral titer and cytopathic effects, an outcome enhanced when both compounds were combined. Quantitative analyses of cell-to-cell fusion and spike processing revealed the key importance of the Furin sites for syncytia formation. Our assays showed that TMPRSS2 enhances fusion and proteolysis at S2’ in the absence of cleavage at S1/S2, an effect that is linked to ACE2 shedding by TMPRSS2. Overall, our results indicate that Furin and TMPRSS2 play synergistic roles in generating fusion-competent S-protein, and in promoting viral entry, supporting the combination of Furin and TMPRSS2 inhibitors as potent antivirals against SARS- CoV-2.
- VIP plasma levels associate with survival in severe COVID-19 patients, correlating with protective effects in SARS- CoV-2-infected cells. -
Infection by SARS-CoV-2 may elicit uncontrolled and damaging inflammatory responses. Thus, it is critical to identify compounds able to inhibit virus replication and thwart the inflammatory reaction. Here, we show that the plasma levels of the immunoregulatory neuropeptide VIP are elevated in patients with severe COVID-19, correlating with reduced inflammatory mediators and with survival on those patients. In vitro, VIP and PACAP, highly similar neuropeptides, decreased the SARS-CoV-2 genome replication in human monocytes and viral production in lung epithelial cells, also reducing cell death. Both neuropeptides inhibited the production of proinflammatory mediators in lung epithelial cells and in monocytes. VIP and PACAP prevented in monocytes the SARS-CoV-2-induced activation of NF-kB and SREBP1 and SREBP2, transcriptions factors involved in proinflammatory reactions and lipid metabolism, respectively. They also promoted CREB activation, a transcription factor with antiapoptotic activity and negative regulator of NF-kB. Specific inhibition of NF-kB and SREBP1/2 reproduced the anti-inflammatory, antiviral and cell death protection effects of VIP and PACAP. Our results support further clinical investigations of these neuropeptides against COVID-19.
- Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection -
A key question in SARS-CoV-2 infection is why viral loads and patient outcomes vary dramatically across individuals. Because spatial-temporal dynamics of viral spread and immuneresponse are challenging to study in vivo, we developed Spatial Immune Model of Coronavirus(SIMCoV), a scalable computational model that simulates hundreds of millions of lung cells, including respiratory epithelial cells and T cells. SIMCoV replicates viral growth dynamics observed in patients and shows how spatially dispersed infections can lead to increased viral loads. The model also shows how the timing and strength of the T cell response can affect viral persistence, oscillations, and control. By incorporating spatial interactions, SIMCoV provides a parsimonious explanation for the dramatically different viral load trajectories among patients by varying only the number of initial sites of infection, and the magnitude and timing of the T cell immune response. When the branching airway structure of the lung is explicitly represented, we find that virus spreads faster than in a 2D layer of epithelial cells, but much more slowly than in an undifferentiated 3D grid or in a well-mixed ODE model. These results illustrate how realistic spatially explicit computational models can improve understanding of within-host dynamics of SARS-CoV-2 infection.
- Evaluation of SARS-CoV-2 Entry, Inflammation and New Therapeutics in Human Lung Tissue Cells -
The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2.
BREATHE: Virtual Self-management for Long COVID-19 - Condition: COVID-19
Intervention: Other: BREATHE
Sponsor:
University of Calgary
Not yet recruiting
COVID-19 Study of Pharmacokinetics, Safety, Tolerability, and Efficacy of Intravenous Anti-Spike(s) SARS-CoV-2 Monoclonal Antibodies (Casirivimab+Imdevimab) for the Treatment of Pediatric Patients Hospitalized Due to COVID-19 - Condition: COVID-19
Intervention: Drug: casirivimab+imdevimab
Sponsor:
Regeneron Pharmaceuticals
Not yet recruiting
JINZHEN for Treatment of Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: JINZHEN Granules for Oral Solution; Drug: Placebo
Sponsor: Lianyungang Kanion Group, Ltd.
Not yet recruiting
Hypertonic Saline Nasal Irrigation and Gargling (HSNIG) for Suspected COVID-19 in Pakistan - Condition: COVID-19
Intervention: Other: Hypertonic Saline Nasal Irrigation and Gargles (HSNIG)
Sponsors: The Allergy and Asthma Institute, Pakistan; University of Edinburgh
Recruiting
Clinical Validation of Breath Analyser Tests for Diagnosis of COVID-19. - Condition: COVID-19
Intervention: Diagnostic Test: Breath Sample analysis
Sponsor: Tera Group
Recruiting
Immunogenicity And Safety of COVID-19 Vaccine , Inactivated Co -Administration With EV71 Vaccine (Vero Cell) - Condition: COVID-19
Intervention: Biological: Experimental Group
Sponsor:
Sinovac Biotech Co., Ltd
Not yet recruiting
A Study to Evaluate Safety & Immunogenicity of SARS-CoV-2 DNA Vaccine Delivered Intramuscularly Followed by Electroporation for COVID-19 - Condition: Covid19
Interventions: Biological: SARS-CoV-2 DNA Vaccine; Biological: Matching placebo
Sponsors: The University of Hong Kong; Immuno Cure 3 Limited
Not yet recruiting
Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 Vaccines Delivered by Aerosol - Conditions: COVID-19; SARS-CoV2 Infection
Interventions: Biological: Ad5-triCoV/Mac; Biological: ChAd-triCoV/Mac
Sponsors: McMaster University; Canadian Institutes of Health Research (CIHR)
Not yet recruiting
Homeopathic Treatment of Post-acute COVID-19 Syndrome - Condition: Post-acute Covid-19 Syndrome
Interventions: Drug: Homeopathic Medication; Other: Placebo
Sponsors: Southwest College of Naturopathic Medicine; Samueli Institute for Information Biology
Recruiting
Effect of PBM on Functional Capacity and Fatigability in Post Covid-19 Elderly - Condition: Post Covid-19 Elderly
Interventions: Radiation: photobiomodulation; Other: placebo intervention by photobiomodulation device
Sponsor: Cairo University
Recruiting
Effectiveness of Interactive Voice Response for COVID-19 Vaccination Training in the Democratic Republic of the Congo - Conditions: COVID-19 Vaccine Knowledge; COVID-19 Vaccine Beliefs and Behaviors
Interventions: Behavioral: COVID-19 Vaccine IVR Training; Behavioral: Control Condition
Sponsors:
Stanford University; Viamo
Not yet recruiting
Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) Booster Study - Condition: COVID-19 Pandemic
Interventions: Biological: Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01); Biological: Blank Preparation of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01)
Sponsor: Livzon Pharmaceutical Group Inc.
Not yet recruiting
Home-based Brain Stimulation Treatment for Post-acute Sequelae of COVID-19 (PASC) - Condition: Post-Acute Sequelae of COVID-19
Interventions: Device: Active tDCS; Device: Sham tDCS
Sponsor: Massachusetts General Hospital
Not yet recruiting
The Effect Of Music On Compliance Of Patients İn COVİD-19 Intensive Care Unit With CPAP Device - Conditions: COVID-19; COVID-19 Acute Respiratory Distress Syndrome
Intervention: Device: Listening to music with a bluetooth headset to patients receiving CPAP support
Sponsors: SÜMEYYE BİLGİLİ; Ataturk University
Recruiting
Ad26.COV2.S as a Heterologous Booster in Adults After Single- or Two-Dose of Inactivated COVID-19 Vaccine - Condition: SARS-CoV-2 Infection
Interventions: Biological: Full dose of Ad26.COV2.; Biological: Half dose of Ad26.COV2.
Sponsors: Mahidol University; National Vaccine Institute, Thailand; International Vaccine Institute; Janssen Pharmaceuticals
Not yet recruiting
Remdesivir; molecular and functional measures of mitochondrial safety - Remdesivir is one of a few antiviral drugs approved for treating severe cases of coronavirus 2 (SARS-CoV-2) infection in hospitalized patients. The prodrug is a nucleoside analog that interferes with viral replication by inhibiting viral RNA-dependent RNA polymerase. The drug has also been shown to be a weak inhibitor of human mitochondrial RNA polymerase, leaving open the possibility of mitochondrial off-targets and toxicity. The investigation was designed to explore whether remdesivir causes…
Understanding the binding mechanism for potential inhibition of SARS-CoV-2 Mpro and exploring the modes of ACE2 inhibition by hydroxychloroquine - As per the World Health Organization report, around 226 844 344 confirmed positive cases and 4 666 334 deaths are reported till September 17, 2021 due to the recent viral outbreak. A novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) is responsible for the associated coronavirus disease (COVID-19), which causes serious or even fatal respiratory tract infection and yet no approved therapeutics or effective treatment is currently available to combat the outbreak. Due…
Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors - Mitogen-activated protein kinase (MAPK) signalling pathways are crucial for developmental processes, oncogenesis, and inflammation, including the production of proinflammatory cytokines caused by reactive oxygen species and upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are no drugs that can effectively prevent excessive inflammatory responses in endothelial cells in the lungs, heart, brain, and kidneys, which are considered the main causes of severe…
Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion - SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gastrointestinal (GI) tract. Diosmectite, an aluminomagnesium silicate adsorbent clay with antidiarrheal effects, is recommended in some COVID-19 management protocols. In rotavirus models, diosmectite prevents…
Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets - Remdesivir is an antiviral approved for COVID-19 treatment, but its wider use is limited by intravenous delivery. An orally bioavailable remdesivir analog may boost therapeutic benefit by facilitating early administration to non- hospitalized patients. This study characterizes the anti-SARS-CoV-2 efficacy of GS-621763, an oral prodrug of remdesivir parent nucleoside GS-441524. Both GS-621763 and GS-441524 inhibit SARS-CoV-2, including variants of concern (VOC) in cell culture and human airway…
alpha-Ketoglutarate Inhibits Thrombosis and Inflammation by Prolyl Hydroxylase-2 Mediated Inactivation of Phospho- Akt - BACKGROUND: Phospho-Akt1 (pAkt1) undergoes prolyl hydroxylation at Pro125 and Pro313 by the prolyl hydroxylase-2 (PHD2) in a reaction decarboxylating α-ketoglutarate (αKG). We investigated whether the αKG supplementation could inhibit Akt- mediated activation of platelets and monocytes, in vitro as well as in vivo, by augmenting PHD2 activity.
The Mpro structure-based modifications of ebselen derivatives for improved antiviral activity against SARS-CoV-2 virus - The main protease (Mpro or 3CLpro) of SARS-CoV-2 virus is a cysteine enzyme critical for viral replication and transcription, thus indicating a potential target for antiviral therapy. A recent repurposing effort has identified ebselen, a multifunctional drug candidate as an inhibitor of Mpro. Our docking of ebselen to the binding pocket of Mpro crystal structure suggests a noncovalent interaction for improvement of potency, antiviral activity and selectivity. To test this hypothesis, we designed…
De novo design of novel protease inhibitor candidates in the treatment of SARS-CoV-2 using deep learning, docking, and molecular dynamic simulations - The main protease of SARS-CoV-2 is a critical target for the design and development of antiviral drugs. 2.5 M compounds were used in this study to train an LSTM generative network via transfer learning in order to identify the four best candidates capable of inhibiting the main proteases in SARS-CoV-2. The network was fine-tuned over ten generations, with each generation resulting in higher binding affinity scores. The binding affinities and interactions between the selected candidates and the…
Molecular docking and simulation studies of synthetic protease inhibitors against COVID-19: a computational study - COVID-19 is the most recent threat to global health. Many people preferred treatment in case of infection instead of vaccination. The inhibition of viral replication is a good strategy for the treatment of COVID-19 infection. 3CLpro and PLpro are two important viral proteases responsible for proteolysis, infection, and replication of the virus. Therefore, targeting of these two enzymes is an attractive way to deal with COVID-19. The aim of this study was to screen some synthetic protease…
Harnessing stress granule formation by small molecules to inhibit the cellular replication of SARS-CoV-2 - We identified small-molecule enhancers of cellular stress granules by observing molecular crowding of proteins and RNAs in a time-dependent manner. Hit molecules sensitized the IRF3-mediated antiviral mechanism in the presence of poly(I:C) and inhibited the replication of SARS-CoV-2 by inducing stress granule formation. Thus, modulating multimolecular crowding can be a promising strategy against SARS-CoV-2.
Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection - The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2’3’-cGAMP associated with STING activation. cGAS…
A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants - The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective…
Auranofin: Past to Present, and repurposing - Auranofin (AF), a gold compound, has been used to treat rheumatoid arthritis (RA) for more than 40 years; however, its mechanism of action remains unknown. We revealed that AF inhibited the induction of proinflammatory proteins and their mRNAs by the inflammatory stimulants, cyclooxygenase-2 and inducible nitric oxide synthase, and their upstream regulator, NF-κB. AF also activated the proteins peroxyredoxin-1, Kelch-like ECH-associated protein 1, and NF-E2-related factor 2, and inhibited…
Methotrexate as a safe immunosuppressive agent during the COVID-19 pandemic - CONCLUSION: The present findings demonstrated that methotrexate does not predispose patients to severe COVID-19; on the contrary, patients taking methotrexate may experience a milder disease, possibly due to their reduced severe inflammatory reactions as a result of inhibited TNFα, lowered IL6, and increased T regulatory cells. According to these findings, methotrexate appears to be a suitable treatment option for patients who need immunosuppressive medications during the COVID-19 pandemic.
An airway organoid-based screen identifies a role for the HIF1alpha-glycolysis axis in SARS-CoV-2 infection - It is urgent to develop disease models to dissect mechanisms regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we derive airway organoids from human pluripotent stem cells (hPSC-AOs). The hPSC-AOs, particularly ciliated-like cells, are permissive to SARS-CoV-2 infection. Using this platform, we perform a high content screen and identify GW6471, which blocks SARS-CoV-2 infection. GW6471 can also block infection of the B.1.351 SARS- CoV-2 variant. RNA…
육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link
휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link
用于检测新冠病毒的配对抗体及其应用 - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用，其包括第一检测抗体和第二检测抗体；第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区，以及如SEQ ID NO:4~6所示的重链互补决定区，第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区，以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体，其识别N蛋白的不同表位，且由于两种抗体识别的是N蛋白非核酸结合区域，不会受核酸负电荷干扰，对核酸抗原表现出了兼容性，具有较好的稳定性，同时上述配对抗体具有较高的亲和力，病毒N蛋白检测灵敏度高。 - link
抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒 - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段，所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域，所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合，基因、重组载体用于抗KL‑6双特异性抗体的制备，药物用于治疗KL‑6蛋白引起的相关疾病，试剂盒用于KL‑6蛋白的定量检测。 - link
基于决策树模型与逻辑回归模型组合的感染筛查方法 - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法，其检测操作方便，可提高感染筛查准确性，该方法基于生命体征监护仪实现，生命体征监护仪与远程数据服务平台通信连接，远程数据服务平台依据临床数据进行感染筛查，该方法包括：通过生命体征监护仪检测获取用户临床数据，将临床数据随机划分为训练集、测试集，将训练集均分为两份：训练集A、训练集B，基于训练集A构建决策树模型，同时，对训练集A进行特征选择，将关键特征向量作为已构建的决策树模型的输入，获取新构造特征向量，基于组合特征向量，构造逻辑回归模型，基于决策树模型和逻辑回归模型组合，对测试集进行预测分类，获取分类结果。 - link
病毒中和抗体与非中和抗体联合检测方法、检测卡及应用 - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用，通过病毒受体结合蛋白夹心法原理检测中和抗体，其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物，将靶向受体蛋白的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题，提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - link
扩增△500-532的SARS-CoV-2 Nsp1基因的引物对及其检测方法 - 本发明公开了一种扩增Δ500‑532的SARS‑CoV‑2 Nsp1基因的引物对及其检测方法。引物对的具体序列如SEQ ID NO.1和SEQ ID NO.2所示，其检测方法为：采用引物对对SARS‑CoV‑2 Nsp1基因进行PCR，对PCR产物进行变性退火后，加入T7EI内切酶孵育，再进行PCR扩增，并判断是否存在Δ500‑532的SARS‑CoV‑2 Nsp1基因。本发明可简便快捷的区分出SARS‑CoV‑2 Nsp1基因突变型和野生型。 - link
多肽及其在新型冠状病毒检测中的应用 - 本发明涉及生物医学领域，具体而言，涉及一种多肽及其在新型冠状病毒检测中的应用。所述多肽包括如下部分：S——Linker——N——avi‑tag。通过经过优化的刚性linker序列把S蛋白和N蛋白串联起来，使得这两个蛋白即具备相对独立的空间构象，又增加了许多优势表位，很大程度上提高了灵敏度和信号值；此外，融合蛋白引入Avi‑tag，使得重组蛋白可以通过固定的位点被固相化，降低包被过程所带来的空间位阻的影响。由此，该多肽能够达到很高的灵敏度和特异性，并且不易发生漏检。 - link