- INTERACTIVE EFFECTS OF AGILE PRACTICES AND PERFORMANCE-TO-CHANGE ON CONSTRUCTION PROJECTS IN MALAYSIAN BUILDING COMPANIES -
Pandemic Covid 19 has altered the perspective on Construction Projects, making them more dynamic. Restriction of activity also exacerbates the challenges associated with construction projects; thus, it is vital to determine how projects may be sustained in their entirety. The purpose of this research was to ascertain the influence of Agile and Business Performance (BP) on Construction Projects (COP) in a period of pandemic covid-19 and community movement constraints. This study route is classified into two categories based on its analysis: direct and indirect influence. This research surveyed 146 respondents from numerous Malaysian construction companies. The study’s primary conclusion is that Agile and Business Performance (BP) factors can influence and Construction Projects (COP) The research adds value because of the test outcomes. Ascertained that a strong management system, Agile, and Business Performance (BP) assistance will improve the performance of construction projects.
- Factors predicting insomnia severity and suicidal thoughts for outpatients, healthcare workers, and the general population in Taiwan during COVID-19 pandemic -
Background: Insomnia and suicidal thoughts are two of negative impacts that have been caused by the COVID-19 pandemic. Identifying the factors that contribute to these psychological problems may help develop strategies to sustain mental health of the public. Aims: The present study examined the psychosocial impacts caused by the COVID-19 pandemic among different populations in Taiwan, and investigated the relationships between these psychosocial factors, insomnia, and suicidal thoughts. Method: Between September 2020 and May 2021, online questionnaires including psychometrically validated scales were distributed to outpatients (n = 205), healthcare workers (HCWs) (n = 500), and individuals in the general population (n = 1200) in Taiwan to collect the data. Multiple linear regression and multivariate logistic regression methods were used to identify potential factors predicting suicidal thoughts and insomnia. Results: Trust in information sources was a significant predictor of suicidal thoughts among outpatients (β = -0.176) and the general population (β = -0.082), and fear of COVID-19 was a significant predictor of suicidal thoughts among HCWs (β = 0.136) and general population (β = 0.142). Resilience was a significant predictor of insomnia among all three populations (outpatients: OR = 0.819, 95% CI = 0.725-0.926; HCWs: OR = 0.803, 95% CI = 0.728-0.887; general population: OR = 0.829, 95% CI = 0.785-0.875). Conclusions: Trust in information sources, fear, and resilience were important factors for suppressing suicide and insomnia among the three study populations. Health policies that monitor psychological status and build resiliency of the public are recommended to help develop tailored strategies for different populations affected by the COVID-19 pandemic.
- Nonlinear control of Covid-19 pandemic based on the SIRD model -
In the last month of 2019, a new version of Corona disease was observed in Wuhan (China) which is known as Covid-19. Several models have been proposed to predict disease treatment. The SIR model is considered one of the simplest models for the prediction of pandemic disease. This means susceptible (S), infected (I), and recovered (R) populations. The SIRD model is yet another method that includes one more equation, i.e., the number of deaths (D). This paper proposed a control law for the first time to prevent the progression of the disease. The proposed control law is based on the SIRD model that is determined using two methods, i.e., the input-state feedback linearization method and the input-output feedback linearization method for the nonlinear modeling of Covid-19. The goal of control in this model is to reduce the percentage or number of infected people and the number of deaths due to Covid-19 disease. Simulation results show that the feedback linearization methods can have positive results in a significant reduction in unfurl of Covid-19. Delay in quarantine of infected people and constant percentage of people who should be quarantined are investigated as two important parameters. Results show that the percentage of infected people decreases 96.3 % and the percentage of deaths decreases 93.6 % when delay in quarantine equals 7 weeks.
- The Omicron variant BA.1.1 presents a lower pathogenicity than B.1 D614G and Delta variants in a feline model of SARS-CoV-2 infection -
Omicron (B.1.1.529) is the most recent SARS-CoV-2 variant of concern (VOC), which emerged in late 2021 and rapidly achieved global predominance in early 2022. In this study, we compared the infection dynamics, tissue tropism and pathogenesis and pathogenicity of SARS-CoV-2 D614G (B.1), Delta (B.1.617.2) and Omicron BA.1.1 sublineage (B.1.1.529) variants in a highly susceptible feline model of infection. While D614G- and Delta-inoculated cats became lethargic, and showed increased body temperatures between days 1 and 3 post-infection (pi), Omicron-inoculated cats remained subclinical and, similar to control animals, gained weight throughout the 14-day experimental period. Intranasal inoculation of cats with D614G- and the Delta variants resulted in high infectious virus shedding in nasal secretions (up to 6.3 log10 TCID50.ml-1), whereas strikingly lower level of viruses shedding (<3.1 log10 TCID50.ml-1) was observed in Omicron-inoculated animals. In addition, tissue distribution of the Omicron variant was markedly reduced in comparison to the D614G and Delta variants, as evidenced by in situ viral RNA detection, in situ immunofluorescence, and quantification of viral loads in tissues on days 3, 5, and 14 pi. Nasal turbinate, trachea, and lung were the main - but not the only - sites of replication for all three viral variants. However, only scarce virus staining and lower viral titers suggest lower levels of viral replication in tissues from Omicron-infected animals. Notably, while D614G- and Delta-inoculated cats had severe pneumonia, histologic examination of the lungs from Omicron-infected cats revealed mild to modest inflammation. Together, these results demonstrate that the Omicron variant BA.1.1 is less pathogenic than D614G and Delta variants in a highly susceptible feline model.
- Oxysterols drive inflammation via GPR183 during influenza virus and SARS-CoV-2 infection -
Rationale: Severe viral respiratory infections are often characterized by extensive myeloid cell infiltration and activation and persistent lung tissue injury. However, the immunological mechanisms driving excessive inflammation in the lung remain elusive. Objectives: To identify the mechanisms that drive immune cell recruitment in the lung during viral respiratory infections and identify novel drug targets to reduce inflammation and disease severity. Methods: Preclinical murine models of influenza virus and SARS-CoV-2 infection. Results: Oxidized cholesterols and the oxysterol-sensing receptor GPR183 were identified as drivers of monocyte-macrophage infiltration to the lung during influenza virus (IAV) and SARS-CoV-2 infections. Both IAV and SARS-CoV-2 infections upregulated the enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily member B1 (CYP7B1) in the lung, resulting in local production of the oxidized cholesterols 25-hydroxycholesterol and 7,25-dihydroxycholesterol (7,25-OHC). Loss-of-function mutation of GPR183, or treatment with a GPR183 antagonist, reduced macrophage infiltration and inflammatory cytokine production in the lungs of IAV- or SARS-CoV-2-infected mice. The GPR183 antagonist also significantly attenuated the severity of SARS-CoV-2 infection by reducing weight loss and viral loads. Conclusion: This study demonstrates that oxysterols drive inflammation in the lung and provides the first preclinical evidence for therapeutic benefit of targeting GPR183 during severe viral respiratory infections.
- A single-component luminescent biosensor for the SARS-CoV-2 spike protein -
Many existing protein detection strategies depend on highly functionalized antibody reagents. A simpler and easier to produce class of detection reagent is highly desirable. We designed a single-component, recombinant, luminescent biosensor that can be expressed in laboratory strains of E. coli and S. cerevisiae. This biosensor is deployed in multiple homogenous and immobilized assay formats to detect recombinant SARS-CoV-2 spike antigen and cultured virus. The chemiluminescent signal generated facilitates detection by an un-augmented cell phone camera. Binding Activated Tandem split-enzyme (BAT) biosensors may serve as a useful template for diagnostics and reagents that detect SARS-CoV-2 antigens and other proteins of interest.
- Mothering and Stress During COVID-19: Exploring the Moderating Effects of Employment -
Using primary data from the Assessing the Social Consequences of COVID-19 study, we examined how the pandemic affected the stress levels of women with and without coresiding minor children (mothers vs. non-mothers), paying special attention to the moderating role of employment status. The OLS regression results show following the pandemic outbreak, among full-time working women, mothers reported smaller stress increases than non-mothers. In contrast, among part-time and non-employed women, mothers and non-mothers experienced similar stress increases. Also, full-time working mothers reported smaller stress increases than women with most other mothering and employment statuses. Changes in women’s employment status, following pandemic onset, had limited impacts on the patterns of stress change. This study contributes to research on parenting and health by showing that during times of crisis, full-time employment may be protective of mothers’ mental health, but may not buffer the mental health deterioration of women not raising children.
- Gender role attitudes cannot explain how British couples responded to increased housework demands during the COVID-19 pandemic -
Previous research has shown that gender role attitudes can predict changes in couples’ housework division over critical life events, but these studies might have suffered from endogeneity because the occurrence of such life events is anticipated and may be affected by gender role attitudes. In contrast, the COVID-19 pandemic was a truly exogenous shock that hit couples unexpectedly. This study examines the role of gender ideologies in how couples adjusted their division of housework during the COVID-19 pandemic in 2020 compared to a pre-pandemic baseline observation. The data cover 3,219 couples from the UK Household Longitudinal Study, with a baseline wave and four COVID-19 panel waves between April and September 2020. We found no evidence that individuals’ or couples’ pre-crisis gender role attitudes affected changes in men’s and women’s absolute or relative contributions to housework at any time during the lockdown. However, both partners spent substantially more time on housework throughout the COVID-19 crisis than before, especially in the early stages, and in relative terms, the pandemic seems to have contributed to at least a temporary, modest increase in gender equality in housework. We discuss our results against the background of previous research whose results may have suffered from endogeneity problems and argue that the COVID-19 ‘shock’ was likely perceived as a merely temporary disruption of couples’ established housework arrangements.
- HIV skews the SARS-CoV-2 B cell response toward an extrafollicular maturation pathway -
Background: HIV infection dysregulates the B cell compartment, affecting memory B cell formation and the antibody response to infection and vaccination. Understanding the B cell response to SARS-CoV-2 in people living with HIV (PLWH) may explain the increased morbidity, reduced vaccine efficacy, reduced clearance, and intra-host evolution of SARS-CoV-2 observed in some HIV-1 coinfections. Methods: We compared B cell responses to COVID-19 in PLWH and HIV negative (HIV-ve) patients in a cohort recruited in Durban, South Africa, during the first pandemic wave in July 2020 using detailed flow cytometry phenotyping of longitudinal samples with markers of B cell maturation, homing and regulatory features. Results: This revealed a coordinated B cell response to COVID-19 that differed significantly between HIV-ve and PLWH. Memory B cells in PLWH displayed evidence of reduced germinal center (GC) activity, homing capacity and class-switching responses, with increased PD-L1 expression, and decreased Tfh frequency. This was mirrored by increased extrafollicular (EF) activity, with dynamic changes in activated double negative (DN2) and activated naive B cells, which correlated with anti-RBD-titres in these individuals. An elevated SARS-CoV-2 specific EF response in PLWH was confirmed using viral spike and RBD bait proteins. Conclusions: Despite similar disease severity, these trends were highest in participants with uncontrolled HIV, implicating HIV in driving these changes. EF B cell responses are rapid but give rise to lower affinity antibodies, less durable long-term memory, and reduced capacity to adapt to new variants. Further work is needed to determine the long-term effects of HIV on SARS-CoV-2 immunity, particularly as new variants emerge.
- DiSCERN - Deep Single Cell Expression ReconstructioN for improved cell clustering and cell subtype and state detection -
Single cell sequencing provides detailed insights into biological processes including cell differentiation and identity. While providing deep cell-specific information, the method suffers from technical constraints, most notably a limited number of expressed genes per cell, which leads to suboptimal clustering and cell type identification. Here we present DISCERN, a novel deep generative network that reconstructs missing single cell gene expression using a reference dataset. DISCERN outperforms competing algorithms in expression inference resulting in greatly improved cell clustering, cell type and activity detection, and insights into the cellular regulation of disease. We used DISCERN to detect two novel COVID-19-associated T cell types, cytotoxic CD4+ and CD8+ Tc2 T helper cells, with a potential role in adverse disease outcome. We utilized T cell fraction information of patient blood to classify mild or severe COVID-19 with an AUROC of 81 % that can serve as a biomarker of disease stage. DISCERN can be easily integrated into existing single cell sequencing workflows and readily adapted to enhance various other biomedical data types.
- Modelling long-term COVID-19 hospital admission dynamics using immune protection waning data -
Immune waning is key to the timely anticipation of COVID-19 long-term dynamics. We assess the impact of periodic vaccination campaigns using a compartmental epidemiological model with multiple age structures and parameterised using empiric time-dependent vaccine protection data. Despite the inherent uncertainty, we show that vaccination on its own, especially if restricted to individuals over 60 years old, seems insufficient to prevent a large number of hospital admissions.
- Social inequality and the risk of being in a nursing home during the COVID-19 pandemic -
BACKGROUND All available evidence suggests that the number of deaths linked to COVID-19 among those living in nursing homes is extremely high. Yet, it remains unknown to what extent there are socio-economic differences among nursing home residents, which can lead, in turn, to social inequality in mortality linked to COVID. OBJECTIVE We investigate whether there are educational differences in the likelihood of living in a nursing home across 13 European countries: Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Italy, the Netherlands, Slovenia, Spain, Sweden, and Switzerland. METHODS We use SHARE data (waves 5-7). We compute logistic regression models for rare events. RESULTS We find that there are sizeable differences in the probability of being in a nursing home, with low-educated individuals more likely to live in this kind of arrangement. This general pattern holds in all the European countries considered. There is considerable uncertainty in our estimates due to small Ns problems and firm conclusions on how the effect of education varies across countries cannot be drawn. Still, there is some indication that the largest educational differences are found in the Scandinavian countries and the smaller ones, even close to zero, in Southern European Countries, with countries in Continental Europe and Eastern Europe laying in between. CONTRIBUTION To the best of our knowledge, this is the first study that provides country specific evidence of educational differences in the probability of being in a nursing home in recent years. In this way, we also provide indirect evidence on social inequality in mortality linked to the COVID-19 pandemic.
- Protective efficacy of COVAXIN(R) against Delta and Omicron variants in hamster model -
The immunity acquired after natural infection or vaccinations against SARS-CoV-2 tend to wane with time. Vaccine effectiveness also varies with the variant of infection. Here, we compared the protective efficacy of COVAXIN following 2 and 3 dose immunizations against the Delta variant and also studied the efficacy of COVAXIN against Omicron variants in a Syrian hamster model. The antibody response, clinical observations, viral load reduction and lung disease severity after virus challenge were studied. Protective response in terms of the reduction in lung viral load and lung lesions were observed in both the 2 dose as well as 3 doses COVAXIN immunized group when compared to placebo group following the Delta variant challenge. In spite of the comparable neutralizing antibody response against the homologous vaccine strain in both the 2 dose and 3 dose immunized groups, considerable reduction in the lung disease severity was observed in the 3 dose immunized group post Delta variant challenge indicating the involvement of cell mediated immune response also in protection. In the vaccine efficacy study against the Omicron variants i.e., BA.1 and BA.2, lesser virus shedding, lung viral load and lung disease severity were observed in the immunized groups in comparison to the placebo groups. The present study shows that administration of COVAXIN booster dose will enhance the vaccine effectiveness against the Delta variant infection and give protection against the Omicron variants BA.1.1 and BA.2.
- Antigenic escape accelerated by the presence of immunocompromised hosts -
The repeated emergence of SARS-CoV-2 escape mutants from host immunity has obstructed the containment of the current pandemic and poses a serious threat to humanity. Prolonged infection in immunocompromised patients has received increasing attention as a driver of immune escape, and accumulating evidence suggests that viral genomic diversity and emergence of immune-escape mutants are promoted in immunocompromised patients. However, because immunocompromised patients comprise a small proportion of the host population, whether they have a significant impact on antigenic evolution at the population level is unknown. We used an evolutionary epidemiological model combining antigenic evolution and epidemiological dynamics in host populations with heterogeneity in immune competency to determine the impact of immunocompromised patients on the pathogen evolutionary dynamics of antigenic escape from host immunity. We derived analytical formulae of the speed of antigenic evolution in heterogeneous host populations and found that even a small number of immunocompromised hosts in the population significantly accelerates antigenic evolution. Our results demonstrate that immunocompromised hosts play a key role in viral adaptation at the population level and emphasize the importance of critical care and surveillance of immunocompromised hosts.
- Optimized intramuscular immunization with VSV-vectored spike protein triggers a superior protective humoral immune response to SARS-CoV-2 -
Immunization with vesicular stomatitis virus (VSV)-vectored COVID-19 vaccine candidates expressing the SARS-CoV-2 spike protein in place of the VSV glycoprotein relies implicitly on expression of the ACE2 receptor at the muscular injection site. Here, we report that such a viral vector vaccine did not induce protective immunity following intramuscular immunization of K18-hACE2 transgenic mice. However, when the viral vector was trans-complemented with the VSV glycoprotein, intramuscular immunization resulted in high titers of spike-specific neutralizing antibodies. The vaccinated animals were fully protected following infection with a lethal dose of SARS-CoV-2-SD614G via the nasal route, and partially protected if challenged with the SARS-CoV-2Delta variant. While dissemination of the challenge virus to the brain was completely inhibited, replication in the lung with consequent lung pathology was not entirely controlled. Thus, intramuscular immunization was clearly enhanced by trans-complementation of the VSV-vectored vaccines by the VSV glycoprotein and led to protection from COVID-19, although not achieving sterilizing immunity.
Phase I Clinical Trial of GEN2-Recombinant COVID-19 Vaccine (CHO Cells) in Healthy People Aged 18 and Above - Condition: COVID-19 Pneumonia
Interventions: Biological: Experimental Vaccine 1; Biological: Experimental Vaccine 2; Biological: Experimental Vaccine 3; Biological: placebo
Sponsors: National Vaccine and Serum Institute, China; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.
Not yet recruiting
COVID-19 Algorithm Treatment at Home - Condition: COVID-19
Interventions: Drug: Recommended treatment schedule; Drug: Usual care
Sponsor: Mario Negri Institute for Pharmacological Research
Not yet recruiting
Immunosuppression and COVID-19 Boosters - Condition: COVID-19
Interventions: Biological: diphtheria and tetanus toxoids (adsorbed) vaccine; Biological: COVID-19 vaccine
Sponsors: Kirby Institute; Seqirus Pty Ltd, Australia; Medical Research Future Fund (MRFF)
Not yet recruiting
Epidemiological Monitoring of COVID-19 Patients Hospitalized on Reunion Island - Condition: COVID-19
Intervention: Other: telephone interview 24 months after hospitalization for Covid-19
Sponsor: Centre Hospitalier Universitaire de la Réunion
Not yet recruiting
α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19 - Condition: COVID-19
Intervention: Other: Real-time Quaking-Induced Conversion (RT-QuIC)
Sponsor: Medical University Innsbruck
Recruiting
Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults - Condition: COVID-19 Vaccines
Interventions: Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech); Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK
Sponsors: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network
Recruiting
Immunogenicity and Safety Study of Booster Vaccine With the COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain - Condition: COVID-19
Intervention: Biological: COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain
Sponsor: Sinovac Biotech (Hong Kong) Limited
Not yet recruiting
Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb) - Conditions: COVID-19 Acute Respiratory Distress Syndrome; COVID-19
Interventions: Drug: Plerixafor 20 MG/ML [Mozobil]; Other: Placebo
Sponsor: 4Living Biotech
Not yet recruiting
Effect of COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men. - Condition: Men Infertility, Post-COVID-19
Intervention: Other: diagnostic test and sperm analysis
Sponsors: Comenius University; GYN-FIV
Active, not recruiting
Calcitriol Supplementation in COVID-19 Patients - Conditions: COVID-19; Vitamin D Deficiency
Intervention: Drug: Calcitriol
Sponsor: RenJi Hospital
Not yet recruiting
Olfactory Training in COVID-19 Associated Loss of Smell - Conditions: COVID-19; Hyposmia
Intervention: Device: Sniffin’ sticks Duftquartett
Sponsor: Medical University Innsbruck
Not yet recruiting
Psychological Impact of Medical Evacuations on Families of Patients Admitted to Intensive Care Unit for Severe COVID-19 - Conditions: COVID-19; Stress Disorders, Post-Traumatic
Interventions: Other: Revised Impact of Event Scale; Other: Hospital Anxiety and Depression scale; Other: 36-Item Short Form Survey; Other: satisfaction survey; Other: semi-directed interview with trusted person on the general experience of the patient’s medical evacuation; Other: semi-directed interview with trusted person on the general experience of hospitalization in intensive care
Sponsor: Centre Hospitalier Metropole Savoie
Completed
Effects of Telerehabilitative Aerobic and Relaxation Exercises Patients With Type 2 Diabetes With and Without COVID-19 - Conditions: COVID-19; Type 2 Diabetes Mellitus
Intervention: Other: Aerobic and Relaxation Exercises
Sponsor: Bozyaka Training and Research Hospital
Active, not recruiting
COVID-19 Vaccine Uptake Trial - Conditions: Vaccination Refusal; COVID-19
Interventions: Other: Short Message Service (SMS) + Website Link Strategy; Other: Phone Call with Peer Strategy
Sponsor: Washington University School of Medicine
Not yet recruiting
Cardiovascular Autonomic and Immune Mechanism of Post COVID-19 Tachycardia Syndrome - Conditions: Post-acute COVID-19 Syndrome; Postural Tachycardia Syndrome (POTS); Long COVID; SARS CoV 2 Infection
Interventions: Diagnostic Test: Determine the inflammatory and immune profile of post-COVID-19 POTS patients; Diagnostic Test: Measurement of PNS activity by HRV (Heart rate Variation); Diagnostic Test: Autonomic Symptoms assessment
Sponsors: Vanderbilt University Medical Center; American Heart Association
Recruiting
The Burden of Hypercoagulability in COVID-19 - The novel coronavirus disease 2019 (COVID-19) infection has widespread impact on multiple organ systems, including damage to endothelial cells. Various studies have found evidence for direct mechanisms by which interaction between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and endothelial cells lead to extensive damage to the latter, and indirect mechanisms, such as excessively elevated cytokines, can also result in the same outcome. Damage to the endothelium results in release…
An L-theanine derivative targets against SARS-CoV-2 and its Delta and Omicron variants - Recent research efforts have shown that tea has activities against SARS-CoV-2. However, the active compounds and the action mechanisms are largely unknown. Here we study the inhibitory potential of L-theanine from tea and its semi-synthesized derivative, a small-molecule fluorescent compound, ethyl 6-bromocoumarin-3-carboxylyl L-theanine (TBrC) against infection and replication of SARS-CoV-2 and the underlying mechanisms of action. We reveal that TBrC has potential activities against SARS-CoV-2…
Papaverine, a promising therapeutic agent for the treatment of COVID-19 patients with underlying cardiovascular diseases (CVDs) - The causative agent of coronavirus disease-2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the host cells via an angiotensin-converting enzyme 2 (ACE2)-mediated endocytosis-dependent manner. Because ACE2 is highly expressed in the heart, SARS-CoV-2 can severely infect heart tissue and arteries, causing acute and chronic damage to the cardiovascular system. Therefore, special attention should be paid to finding appropriate agents to protect this vital system…
Therapeutic efficacy of monoclonal antibodies and antivirals against SARS-CoV-2 Omicron BA.1 in Syrian hamsters - The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major antigen stimulating the host’s protective immune response. Here we assessed the efficacy of therapeutic monoclonal antibodies (mAbs) against Omicron variant (B.1.1.529) sublineage BA.1 variants in Syrian hamsters. Of the FDA-approved therapeutic mAbs tested (that is, REGN10987/REGN10933, COV2-2196/COV2-2130 and S309), only COV2-2196/COV2-2130 efficiently inhibited BA.1 replication in the lungs of…
Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants - The novel SARS-CoV-2 variants of concern (VOC) represent a considerable global alarm because their mutations are known to affect transmissibility and cause immune escape. While preventing severe disease and deaths, the available vaccines do not avoid infection; therefore, COVID-19 disease management still requires effective therapies. We have recently reported that the aminothiol cysteamine, a drug already applied to humans, exerts direct antiviral activity against SARS-CoV-2 and has in vitro…
Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells - An essential step in the infection life cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the proteolytic activation of the viral spike (S) protein, which enables membrane fusion and entry into the host cell. Two distinct classes of host proteases have been implicated in the S protein activation step: cell-surface serine proteases, such as the cell-surface transmembrane protease, serine 2 (TMPRSS2), and endosomal cathepsins, leading to entry through either the…
The antiviral targeting potential of viroporins - Viroporins are ion channels found in many viruses, where they contribute to virus life cycle and thereby pathogenesis. Viroporin targeting is a known, yet largely unexplored, therapeutic strategy so far only used in Influenza A with the drugs amantadine and rimantadine. In this review, we seek to utilize the inhibition by amantadine of the viroporin Protein E in SARS-CoV-2 in an attempt to treat COVID-19 in its early stages. We are executing a double-blinded placebo-controlled trial based on…
Molecular modelling and simulation techniques to investigate the effects of fungal metabolites on the SARS-CoV-2 RdRp protein inhibition - Various protein/receptor targets have been discovered through in-silico research. They are expanding rapidly due to their extensive advantage of delivering new drug candidates more quickly, efficiently, and at a lower cost. The automation of organic synthesis and biochemical screening will lead to a revolution in the entire research arena in drug discovery. In this research article, a few fungal metabolites were examined through an in-silico approach which involves major steps such as (a)…
Different Aspects of Emetine’s Capabilities as a Highly Potent SARS-CoV-2 Inhibitor against COVID-19 - In the global movement to find the appropriate agents to fight the coronavirus disease of 2019 (COVID-19), emetine is one of the strongest anti-SARS-CoV-2 compounds with sub-micromolar EC(50) values, identified in several studies and high-throughput screening efforts. The reported anti-SARS-CoV-2 mechanisms indicate the effect of this compound on both virus-based and host-based targets. In addition to having excellent antiviral effects, emetine can relieve COVID-19 patients by reducing…
Acrylamide fragment inhibitors that induce unprecedented conformational distortions in enterovirus 71 3C and SARS-CoV-2 main protease - RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3C^(pro)) of…
ARF6 is an important host factor for SARS-CoV-2 infection in vitro - SARS-CoV-2 is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors, and the mechanism of fusion of the virus at the plasma membrane have been extensively investigated, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the…
Exploring the phytochemicals of Platycodon grandiflorus for TMPRSS2 inhibition in the search for SARS-CoV-2 entry inhibitors - Platycodon grandiflorus (Jacq.) A. DC. (Campanulaceae) is commonly known as a balloon flower whose rhizomes have been widely utilized in traditional Chinese medicine (TCM) and in various Japanese prescriptions for the treatment of respiratory diseases, diabetes, and inflammatory disorders. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) global pandemic requires priming of the virus’s spike (S) protein by cleavage of the…
Structure, receptor recognition, and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein - The isolation of CCoV-HuPn-2018 from a child respiratory swab indicates that more coronaviruses are spilling over to humans than previously appreciated. We determined the structures of the CCoV-HuPn-2018 spike glycoprotein trimer in two distinct conformational states and showed that its domain 0 recognizes sialosides. We identified that the CCoV-HuPn-2018 spike binds canine, feline, and porcine aminopeptidase N (APN) orthologs, which serve as entry receptors, and determined the structure of the…
Zirconium-Based Metal-Organic Frameworks as Acriflavine Cargos in the Battle against Coronaviruses─A Theoretical and Experimental Approach - In this study, we present a complementary approach for obtaining an effective drug, based on acriflavine (ACF) and zirconium-based metal-organic frameworks (MOFs), against SARS-CoV-2. The experimental results showed that acriflavine inhibits the interaction between viral receptor-binding domain (RBD) of spike protein and angiotensin converting enzyme-2 (ACE2) host receptor driving viral cell entry. The prepared ACF@MOF composites exhibited low (MOF-808 and UiO-66) and high (UiO-67 and NU-1000)…
Significant role of host sialylated glycans in the infection and spread of severe acute respiratory syndrome coronavirus 2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been transmitted across all over the world, in contrast to the limited epidemic of genetically- and virologically-related SARS-CoV. However, the molecular basis explaining the difference in the virological characteristics among SARS-CoV-2 and SARS-CoV has been poorly defined. Here we identified that host sialoglycans play a significant role in the efficient spread of SARS-CoV-2 infection, while this was not the case with SARS-CoV….