- Online Learning Quality, Satisfaction, and Word-of-Mouth Promotion -
This study aimed to verify and analyze the two influences. The first was the effect of online learning quality (OLQ) on student satisfaction and word-of-mouth (WOM) promotion. The second was the impact of student satisfaction on WOM promotion. Then, we used the population of 137 students taking online classes during the COVID-19 pandemic at Indonesia’s Interkultural Edukasi Partner (IEP) in Bandung to support this intention. Furthermore, we applied the Slovin formula with a 5% border of fault to obtain a sample size of 103. After getting it, the samples were taken by simple random sampling. Unfortunately, only 45 students responded by filling out the questionnaire distributed. As a result, this study utilized the structural equation model based on variance to examine the proposed hypotheses. After testing and discussing them, this research concluded that OLQ positively influenced student satisfaction, but OLQ did not. Besides, student satisfaction positively affected this promotion.
- Predicting the antigenic evolution of SARS-COV-2 with deep learning -
The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) antigenic profile evolves in response to the vaccine and natural infection-derived immune pressure, resulting in immune escape and threatening public health. Exploring the possible antigenic evolutionary potentials improves public health preparedness, but it is limited by the lack of experimental assays as the sequence space is exponentially large. Here we introduce the Machine Learning-guided Antigenic Evolution Prediction (MLAEP), which combines structure modeling, multi-task learning, and genetic algorithm to model the viral fitness landscape and explore the antigenic evolution via in silico directed evolution. As demonstrated by existing SARS-COV-2 variants, MLEAP can infer the order of variants along antigenic evolutionary trajectories, which is also strongly correlated with their sampling time. The novel mutations predicted by MLEAP are also found in immunocompromised covid patients and newly emerging variants, like BA. 4/5. In sum, our approach enables profiling existing variants and forecasting prospective antigenic variants, thus may help guide the development of vaccines and increase preparedness against future variants.
- A cell-based, spike protein binding assay highlights differences in antibody neutralising capacity for SARS-CoV-2 variants -
The engagement of the SARS-CoV-2 spike protein with ACE2 is a critical step for viral entry to human cells and accordingly blocking this interaction is a major determinant of the efficacy of monoclonal antibody therapeutics and vaccine-elicited serum antibodies. The emergence of SARS-CoV-2 variants necessitates the development of adaptable assays that can be applied to assess the effectiveness of therapeutics. Through testing of a range of recombinant spike proteins, we have developed a cell based, ACE2/spike protein binding assay that characterises monoclonal anti-spike protein antibodies and neutralising antibodies in donor serum. The assay uses high-content imaging to quantify cell bound spike protein fluorescence. Using spike proteins from the original “Wuhan” SARS-CoV-2 virus, as well as the delta and omicron variants, we identify differential blocking activity of three monoclonal antibodies directed against the spike receptor binding domain. Importantly, biological activity in the spike binding assay translated to efficacy in a SARS-CoV-2 infection assay. Hence, the spike binding assay has utility to monitor anti-spike antibodies against the major known SARS-CoV-2 variants and is readily adaptable to quantify impact of antibodies against new and emerging SARS-CoV-2 variants.
- Investigating the mutations in the SARS-CoV-2 proteins among European countries -
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new member of the Coronaviridae family, triggering more than 190 million cases and more than two million deaths in European societies. Emerging the new variants due to mutations in genomic regions are foremost responsible for influencing the infectivity and mortality potential of such a virus. In the current study, we considered mutations among spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 in the Europe continent by exploring the frequencies of mutations and the timeline of emerging them. For this purpose, Amino-acid sequences (AASs) were gathered from the GISAID database, and Mutation tracking was performed by detecting any difference between samples and a reference sequence; Wuhan-2019. In the next step, we compared the achieved results with worldwide sequences. 8.6%, 63.6%, 24.7%, and 1.7% of S, E, M, and N samples did not demonstrate any mutation among European countries. Also, the regions of 508 to 635 AA, 7 to 14 AA, 66 to 88 AA, and 164 to 205 AA in S, E, M, and N samples contained the most mutations relative to the total AASs in both Europe AASs and worldwide samples. D614G, A222V, S477N, and L18F were the first to fifth frequent mutations in S AASs among European samples, and T9I, I82T, and R203M were the first frequent mutations among E, M, and S AASs of the Europe continent. Investigating the mutations among structural proteins of SARS-CoV-2 can improve the strength of therapeutic and diagnostic strategies to efficient combat the virus and even maybe efficient in predicting new emerging variants of concern.
- DESIGN OF A CHIMERIC ACE-2/Fc-SILENT FUSION PROTEIN WITH ULTRAHIGH AFFINITY AND NEUTRALIZING CAPACITY FOR SARS-CoV-2 VARIANTS -
As the coronavirus SARS-CoV-2 continues to mutate into Variants of Concern (VOC), there is a growing and urgent need to develop effective antivirals to combat the newly emerged infectious disease COVID-19. Recent data indicate that monoclonal antibodies developed early in the pandemic are no longer capable of effectively neutralizing currently active VOCs. This report describes the design of a class of variant-agnostic chimeric molecules consisting of an Angiotensin Converting Enzyme-2 (ACE-2) domain mutated to retain ultrahigh affinity binding to a wide variety of SARS-CoV-2 variants, coupled to an Fc-silent immunoglobulin domain that eliminates antibody-dependent enhancement (ADE) and simultaneously extends biological half-life compared to existing mABs. Molecular modeling revealed that ACE-2 mutations L27, V34 and E90 resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM, 507 pM and 73 pM for binding to the Alpha B1.1.7, Delta B.1.617.2 and Omicron B.1.1.529 variants, and notably, 78fM affinity to the Omicron BA.2 variant, respectively. Surrogate viral neutralization assays (sVNT) revealed titers of [≥]4.9ng/ml, for neutralization of recombinant viral proteins corresponding to the Alpha, Delta and Omicron variants. The values above were obtained with LVE-ACE-2/mAB chimeras containing the Y-T-E sequence that enhances binding to the FcRn receptor, which in turn is expected to extend biological half-life 3-4-fold. It is proposed that this new class of chimeric ACE-2/mABs will constitute variant-agnostic and cost-effective prophylactics against SARS-CoV-2, particularly when administered by nasal delivery systems.
- Monitoring SARS-CoV-2 infection using a double reporter-expressing virus -
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the highly contagious agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. An essential requirement for understanding SARS-CoV-2 fundamental biology and the impact of anti-viral therapeutics are robust methods to detect for the presence of the virus in infected cells or animal models. Despite the development and successful generation of recombinant (r)SARS-CoV-2 expressing fluorescent or luciferase reporter genes, knowledge acquired from their use in in vitro assays and/or in live animals are limited to the properties of the fluorescent or luciferase reporter genes. Herein, for the first time, we engineered a replication-competent rSARS-CoV-2 that expresses both fluorescent (mCherry) and luciferase (Nluc) reporter genes (rSARS-CoV-2/mCherry-Nluc) to overcome limitations associated with the use of a single reporter gene. In cultured cells, rSARS-CoV-2/mCherry-Nluc displayed similar viral fitness as rSARS-CoV-2 expressing single reporter fluorescent and luciferase genes (rSARS-CoV-2/mCherry and rSARS-CoV-2/Nluc, respectively), or wild-type (WT) rSARS-CoV-2, while maintaining comparable expression levels of both reporter genes. In vivo, rSARS-CoV-2/mCherry-Nluc has similar pathogenicity in K18 human angiotensin converting enzyme 2 (hACE2) transgenic mice than rSARS-CoV-2 expressing individual reporter genes, or WT rSARS-CoV-2. Importantly, rSARS-CoV-2/mCherry-Nluc facilitates the assessment of viral infection and transmission in golden Syrian hamsters using in vivo imaging systems (IVIS). Altogether, this study demonstrates the feasibility of using this novel bireporter-expressing rSARS-CoV-2 for the study SARS-CoV-2 in vitro and in vivo.
- The Functional Landscape of SARS-CoV-2 3CL Protease -
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) as the etiologic agent of COVID-19 (coronavirus disease 2019) has drastically altered life globally. Numerous efforts have been placed on the development of therapeutics to treat SARS-CoV-2 infection. One particular target is the 3CL protease (3CLpro), which holds promise as it is essential to the virus and highly conserved among coronaviruses, suggesting that it may be possible to find broad inhibitors that treat not just SARS-CoV-2 but other coronavirus infections as well. While the 3CL protease has been studied by many groups for SARS-CoV-2 and other coronaviruses, our understanding of its tolerance to mutations is limited, knowledge which is particularly important as 3CL protease inhibitors become utilized clinically. Here, we develop a yeast-based deep mutational scanning approach to systematically profile the activity of all possible single mutants of the SARS-CoV-2 3CLpro, and validate our results both in yeast and in authentic viruses. We reveal that the 3CLpro is highly malleable and is capable of tolerating mutations throughout the protein, including within the substrate binding pocket. Yet, we also identify specific residues that appear immutable for function of the protease, suggesting that these interactions may be novel targets for the design of future 3CLpro inhibitors. Finally, we utilize our screening results as a basis to identify E166V as a resistance-conferring mutation against the therapeutic 3CLpro inhibitor, nirmatrelvir, in clinical use. Collectively, the functional map presented herein may serve as a guide for further understanding of the biological properties of the 3CL protease and for drug development for current and future coronavirus pandemics.
- In Vitro Evaluation and Mitigation of Niclosamide Liabilities as a COVID-19 Treatment. -
Niclosamide, an FDA-approved oral anthelmintic drug, has broad biological activity including anticancer, antibacterial, and antiviral properties. Niclosamide has also been identified as a potent inhibitor of SARS-CoV-2 infection in vitro, generating interest in its use for the treatment or prevention of COVID-19. Unfortunately, there are several potential issues with using niclosamide for COVID-19, including low bioavailability, significant polypharmacology, high cellular toxicity, and unknown efficacy against emerging SARS-CoV-2 variants of concern. In this study, we used high-content imaging-based immunofluorescence assays in two different cell models to assess these limitations and evaluate the potential for using niclosamide as a COVID-19 antiviral. We show that despite promising preliminary reports, the antiviral efficacy of niclosamide overlaps with its cytotoxicity giving it a poor in vitro selectivity index for anti-SARS-CoV-2 inhibition. We also show that niclosamide has significantly variable potency against the different SARS-CoV-2 variants of concern and is most potent against variants with enhanced cell-to-cell spread including B.1.1.7. Finally, we report the activity of 33 niclosamide analogs, several of which have reduced cytotoxicity and increased potency relative to niclosamide. A preliminary structure-activity relationship analysis reveals dependence on a protonophore for antiviral efficacy, which implicates nonspecific endolysosomal neutralization as a dominant mechanism of action. Further single-cell morphological profiling suggests niclosamide also inhibits viral entry and cell-to-cell spread by syncytia. Altogether, our results suggest that niclosamide is not an ideal candidate for the treatment of COVID-19, but that there is potential for developing improved analogs with higher clinical translational potential in the future.
- The effect of proximity of COVID-19 test facilities on test uptake: Two quasi-experimental trials -
Background: Test, Trace and Isolate (TTI) is a key strategy in the SARS-CoV-2 pandemic response. There is limited experimental evidence on how to improve uptake of COVID-19 testing. In this study we manipulate test site proximity to evaluate its impact on test uptake. Methods: We conducted two quasi-experimental studies (from February 8th to March 21st, 2021) during a community-wide testing initiative in The Netherlands. In Study 1 we placed a test site in one village (reducing distance to test site from 8.4km to 800m) but not in a matched control village (distance to test site 9.9km). In Study 2 a mobile test bus alternated between two areas codes, changing distance to the test site from 3.5km to 200m and from 1.6km to 850m. The trial is registered at the Netherlands Trial Register (number NL9365). Findings: In Study 1 (n=11,317 eligible inhabitants), a logistic regression controlling for baseline differences (8.6% control vs 10% intervention) found a significant effect of reducing test site proximity (17.5% control vs 29% intervention) [Odds Ratio =1.84 {95% CI 1.68-2.02}]; p < 0.0001]. In Study 2 (n=1,880 eligible inhabitations), a Poisson regression revealed higher test uptake when the mobile test bus was present (33.6% when absent vs 42.6% when present, Incidence Rate Ratio = 1.35, [95% CI 1.14-1.59]; p < 0.0001). Interpretation: Reducing the distance to COVID-19 test facilities increased test uptake, at least when the distance was reduced from an average of 3.5km to 200 metres. Localising test facilities can substantially increase testing for COVID-19, and thus the effectiveness of TTI in general. Funding: The Ministry of Health, Welfare and Sport (VWS) of the Netherlands.
- Early Experience Unpredictability in Child Development as a Model for Understanding the Impact of the COVID-19 Pandemic: A Translational Neuroscience Perspective -
Extensive evidence links adverse experiences during childhood to a wide range of negative consequences in biological, socioemotional, and cognitive development. Unpredictability is a core element underlying most forms of early adversity; it has been a focus of developmental research for many years and has been receiving increasing attention recently. In this article, we propose a conceptual model to describe how unpredictable and adverse early experiences affect children’s neurobiological, behavioral, and psychological development in the context of the COVID-19 pandemic. We first highlight the critical role of unpredictability in child development by reviewing existing conceptual models of early adversity as they relate to subsequent development across the lifespan. Then, we employ a translational neuroscience framework to summarize the current animal- and human-based evidence on the neurobiological alterations induced by early experience unpredictability. We further argue that the COVID-19 pandemic serves as a global “natural experiment” that provides rare insight to the investigation of the negative developmental consequences of widespread, clustered, and unpredictable adverse events among children. We discuss how the pandemic helps advance the science of unpredictable early adverse experiences. As unpredictability research continues to grow, we highlight several directions for future studies and implications for policymaking and intervention practices.
- Modeling and leveraging intuitive theories to improve vaccine attitudes -
Much of the richness of human thought is supported by people’s intuitive theories—mental frameworks capturing the perceived structure of the world. But intuitive theories can also contain and reinforce dangerous misconceptions. In this paper, we take up the case of misconceptions about vaccine safety that discourage vaccination. These misconceptions constitute a major public health risk that predates the coronavirus pandemic but that has become all the more dire in recent years. We argue that addressing such misconceptions requires awareness of the broader conceptual contexts in which they are embedded. To build this understanding, we examined the structure and revision of people’s intuitive theories of vaccination in five large survey studies (total N = 3196). Based on these data, we present a cognitive model of the intuitive theory surrounding people’s decisions about whether to vaccinate young children against diseases like measles, mumps, and rubella (MMR). Using this model, we were able to make accurate predictions about how people’s beliefs would be revised in light of educational interventions, design an effective new intervention encouraging vaccination, and understand how these beliefs were affected by real-world events (the measles outbreaks of 2019). In addition to presenting a promising way forward for promoting the MMR vaccine, this approach has clear implications for encouraging the uptake of COVID-19 vaccines, especially among parents of young children. At the same time, this work provides the foundation for richer understandings of intuitive theories and belief revision more broadly.
- Two Sides of the Same Coin: A Mixed Methods Study of Black Mothers’ Experiences with Violence, Stressors, Parenting, and Coping during the COVID-19 Pandemic -
Due to systemic and structural inequities, the COVID-19 pandemic disproportionately impacts the Black community, along with ongoing anti-Black racism and violence. Violence against women in the home, particularly Black women, was prevalent during shelter in place, along with the additional family responsibilities of Black mothers. Crenshaw’s theory of intersectionality (1991) provides a foundation for examining Black mothers’ experiences during shelter-in-place mandates. This mixed-methods study aimed to quantitatively assess violence victimization, acknowledged racial inequities, depression and anxiety, while qualitatively examining Black mothers’ experiences in parenting during shelter-in-place orders. Participants (N = 127; Mage = 32.4 years) were mothers who self-identify as Black or African American living in a Midwestern US city. Results showed that Black mothers who perceived greater COVID-19 inequities in the Black community reported increased parental stress, decreased emotional support, greater exposure to physical or sexual violence, and higher symptoms of stress, anxiety, and depression. Qualitative results yielded numerous themes, including the integrative theme of two sides of the same coin, highlighting both positive parenting experiences and significant stressors for Black mothers. The implications point to the need for intersectional and feminist approaches to interventions and initiatives that support Black women as humans, mothers, souls, and spirits.
- Double Jab: Survey Evidence on Vaccine Hesitancy, Beliefs, and Attitudes in India -
India witnessed a large surge in COVID-19 cases in April 2021, a second wave of nearly 350,000 daily new infections across the country. As of December 2021, cases have reduced drastically, in part due to greater vaccine coverage across the country. This study reports results on vaccine hesitancy, attitudes, and behaviors from an online survey conducted between February and March 2021 in nine Indian cities (N = 518). We find that vaccine hesitancy negatively predicts willingness to take the vaccine, and beliefs about vaccine effectiveness supersede hesitancy in explaining vaccine uptake. Furthermore, we find that mask-wearing and handwashing beliefs, information sources related to COVID-19, and past COVID-19 infection and testing status are all strongly associated with the hypothetical choice of vaccine. We discuss these findings in the context of behavioral theories as well as outline implications for vaccine-related health communication in India.
- Psychosocial, economic, and mental health predictors of COVID-19 vaccine intent -
Introduction: Coronavirus vaccines remain the most effective protection against COVID-19. However, many people are hesitant to be vaccinated. It is necessary to understand factors that lead to unwillingness to be vaccinated to ensure most Americans receive the vaccine. Methods: Participants completed a series of online surveys asking about the vaccine and the physical, social, economic, and mental health effects of COVID-19. Baseline responses were entered into a logistic regression model to identify psychosocial, economic and physical factors that had an impact on vaccine intent. Results: The model revealed participants were more willing to be vaccinated if they spent time reading or talking about COVID, feared COVID infection, had health insurance or had a family member suffer a COVID-19 infection. Conclusion: COVID-19 vaccine intent is closely connected to one’s personal experience of the pandemic. It is crucial to disseminate factual information about the benefits and risks of both COVID-19 and vaccination.
- On social health: Conceptualization, Correlates and Patterning -
Drawing upon extensive literature on the importance of social relationships from across social science and health disciplines, we propose a strong conceptualization of social health as a dynamic and multifaceted construct with the ability to expand and focus theory, research and practice. We define social health as the perceived and actual availability and quality of one’s various social relationships. Using this conceptualization, we demonstrate how a tripartite model of health, situated within the human body (and mind), best explains well-documented interrelationships between physical, psychological and social aspects of health. In order to describe the utility and importance of social health, we discuss its significance to understanding and addressing population health concerns, especially health inequalities, as well as recent major global events, including the rise of “deaths of despair” and the COVID-19 pandemic. By renewing research on social health under the framework presented herein, scholars can unify disparate lines of work on constructs ranging from loneliness and social integration to close relationship quality and social capital. Moreover, we argue that adoption of the concept of social health is critical to the success of nations, states and health systems across societies in guaranteeing an optimal state of health for all.
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
Discussing COVID-19 Vaccines in Private Facebook Groups - Condition: COVID-19
Interventions: Behavioral: Gist messages on COVID-19 vaccination; Behavioral: COVID-19 vaccine information
Sponsor: George Washington University
Completed
Home-Based Exercise Tele-Rehabilitation After COVID-19 - Condition: Post SARS-CoV2 (COVID-19)
Intervention: Other: Tele-exercise
Sponsors: VA Office of Research and Development; Baltimore Veterans Affairs Medical Center; Salem Veterans Affairs Medical Center
Not yet recruiting
IMM-BCP-01 in Mild to Moderate COVID-19 - Conditions: SARS-CoV2 Infection; COVID-19
Interventions: Drug: IMM-BCP-01; Drug: Placebo
Sponsors: Immunome, Inc.; United States Department of Defense
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
Effect of COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men. - Conditions: Infertility, Male; COVID-19
Intervention: Other: diagnostic test and sperm analysis
Sponsors: Comenius University; GYN-FIV
Active, not recruiting
A Study to Evaluate Immunogenicity and Safety of MVC-COV1901 Vaccine Compared With AZD1222 - Condition: COVID-19 Vaccine
Interventions: Biological: MVC-COV1901; Biological: AZD1222
Sponsor: Medigen Vaccine Biologics Corp.
Not yet 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
Laser Therapy on Tension-type Cephalea and Orofacial Pain in Post-covid-19 Patients - Conditions: Tension-Type Headache; Orofacial Pain; COVID-19
Intervention: Radiation: Photobimodulation
Sponsor: University of Nove de Julho
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
Clinical Trial of SARS-CoV-2 mRNA Vaccine(LVRNA009) as Heterologous Booster in Islamabad - Condition: SARS-CoV-2
Interventions: Biological: LVRNA009; Biological: CoronaVac®
Sponsor: AIM Vaccine Co., Ltd.
Not yet recruiting
STEP-COVID: A Program for Pregnant Women During the SARS-CoV-2 Pandemic - Conditions: Psychological; Mental Health Issue; Prenatal Stress; Maternal Distress; COVID-19 Pandemic
Intervention: Behavioral: STEP-COVID
Sponsors: Université du Québec à Trois-Rivières; Public Health Agency of Canada (PHAC); Canada Research Chairs Endowment of the Federal Government of Canada
Active, not recruiting
Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers - Condition: COVID-19
Interventions: Drug: HLX70; Drug: Placebo
Sponsors: Shanghai Henlius Biotech; Hengenix Biotech Inc; Sanyou Biopharmaceuticals(Shanghai)Co., Ltd; Shanghai ZJ Bio-Tech Co., Ltd
Withdrawn
Matched Versus Mixed COVID-19 Vaccinations in Korean Solid Organ Transplant Recipients: An Observational Study - CONCLUSIONS: The ChAd/BNT group showed higher humoral immunogenicity than the AdV-Vec group, with similar immunogenicity to the mRNA vaccine. Nevertheless, immunogenicity following the primary vaccination series was poor in all vaccine groups, supporting the justification for booster vaccination in SOTRs.
Rationale of using the dual chemokine receptor CCR2/CCR5 inhibitor cenicriviroc for the treatment of COVID-19 - Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created a global pandemic infecting over 230 million people and costing millions of lives. Therapies to attenuate severe disease are desperately needed. Cenicriviroc (CVC), a C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 2 (CCR2) antagonist, an agent previously studied in advanced clinical trials for patients with HIV or nonalcoholic steatohepatitis (NASH), may…
A universal DNA aptamer as an efficient inhibitor against spike-protein/hACE2 interactions - A universal aptamer against spike-proteins of diverse SARS-CoV-2 variants was discovered via DNA SELEX towards the wild-type (WT) spike-protein. This aptamer, A1C1, binds to the WT spike-protein or other variants of concern such as Delta and Omicron with low nanomolar affinities. A1C1 inhibited the interaction between hACE2 and various spike-proteins by 85-89%. This universal A1C1 aptamer can be used to design diagnostic and therapeutic molecular tools to target SARS-CoV-2 and its variants.
SARS-CoV-2 M Protein Facilitates Malignant Transformation of Breast Cancer Cells - Coronavirus disease 2019 (COVID-19) has spread faster due to the emergence of SARS-CoV-2 variants, which carry an increased risk of infecting patients with comorbidities, such as breast cancer. However, there are still few reports on the effects of SARS-CoV-2 infection on the progression of breast cancer, as well as the factors and mechanisms involved. In the present study, we investigated the impact of SARS-CoV-2 proteins on breast cancer cells (BCC). The results suggested that SARS-CoV-2 M…
Antifibrotic Mechanism of Piceatannol in Bleomycin-Induced Pulmonary Fibrosis in Mice - Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by myofibroblast accumulation and extracellular matrix deposition, which lead to irreversible damage of the lung’s architecture and the formation of fibrotic lesions. IPF is also a sequela in serious patients with the coronavirus disease 2019 (COVID-19). The molecular mechanisms under pulmonary fibrosis remain unclear, and there is no satisfactory treatment currently available….
Inhibitors of Activin Receptor-like Kinase 5 Interfere with SARS-CoV-2 S-Protein Processing and Spike-Mediated Cell Fusion via Attenuation of Furin Expression - Screening of a protein kinase inhibitor library identified SB431542, targeting activin receptor-like kinase 5 (ALK5), as a compound interfering with SARS-CoV-2 replication. Since ALK5 is implicated in transforming growth factor β (TGF-β) signaling and regulation of the cellular endoprotease furin, we pursued this research to clarify the role of this protein kinase for SARS-CoV-2 infection. We show that TGF-β1 induces the expression of furin in a broad spectrum of cells including Huh-7 and Calu-3…
Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses - In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study…
Nucleopore Traffic Is Hindered by SARS-CoV-2 ORF6 Protein to Efficiently Suppress IFN-β and IL-6 Secretion - A weak production of INF-β along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins that are able to counteract the host immune system, which is believed to be one of the most important features contributing to the viral pathogenesis and development of a severe clinical outcomes. Previous reports demonstrated that the SARS-CoV-2 ORF6 protein strongly suppresses INF-β production by…
High Incidence of SARS-CoV-2 Variant of Concern Breakthrough Infections Despite Residual Humoral and Cellular Immunity Induced by BNT162b2 Vaccination in Healthcare Workers: A Long-Term Follow-Up Study in Belgium - To mitigate the massive COVID-19 burden caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccination campaigns were initiated. We performed a single-center observational trial to monitor the mid- (3 months) and long-term (10 months) adaptive immune response and to document breakthrough infections (BTI) in healthcare workers (n = 84) upon BNT162b2 vaccination in a real-world setting. Firstly, serology was determined through immunoassays. Secondly, antibody…
Characterization of SARS-CoV-2 Evasion: Interferon Pathway and Therapeutic Options - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. SARS-CoV-2 is characterized by an important capacity to circumvent the innate immune response. The early interferon (IFN) response is necessary to establish a robust antiviral state. However, this response is weak and delayed in COVID-19 patients, along with massive pro-inflammatory cytokine production. This dysregulated innate immune response contributes to pathogenicity and in some…
Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds - Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic…
Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19 - Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging…
In Silico Screening and Testing of FDA-Approved Small Molecules to Block SARS-CoV-2 Entry to the Host Cell by Inhibiting Spike Protein Cleavage - The COVID-19 pandemic began in 2019, but it is still active. The development of an effective vaccine reduced the number of deaths; however, a treatment is still needed. Here, we aimed to inhibit viral entry to the host cell by inhibiting spike (S) protein cleavage by several proteases. We developed a computational pipeline to repurpose FDA-approved drugs to inhibit protease activity and thus prevent S protein cleavage. We tested some of our drug candidates and demonstrated a decrease in protease…
The AI-Assisted Identification and Clinical Efficacy of Baricitinib in the Treatment of COVID-19 - During the current pandemic, the vast majority of COVID-19 patients experienced mild symptoms, but some had a potentially fatal aberrant hyperinflammatory immune reaction characterized by high levels of IL-6 and other cytokines. Modulation of this immune reaction has proven to be the only method of reducing mortality in severe and critical COVID-19. The anti-inflammatory drug baricitinib (Olumiant) has recently been strongly recommended by the WHO for use in COVID-19 patients because it reduces…
A Randomized Clinical Trial of a Fractional Low Dose of BNT162b2 Booster in Adults Following AZD1222 - In the era of globally predominant omicron strains, a COVID-19 booster vaccine is needed. Our study aimed to evaluate the immunogenicity of a half-dose BNT162b2 booster after AZD1222 in healthy adults. A randomized trial of volunteers aged 18-69 years who received two-dose AZD1222 was conducted. The participants were randomized to receive the BNT162b2 vaccine intramuscularly-half (15 µg) vs. standard dose (30 µg). The immunogenicity was evaluated by a surrogate virus neutralization test (sVNT)…