- Who Is the Most Stressed During COVID-19 Isolation? Data From 27 Countries -
****************** ***************************** ****************** ************************ ***** This is old, not peer-reviewed version of the manuscript. For published version, please visit: https://doi.org/10.1111/aphw.12234 *********************************************** ****************** ************** *********** **** To limit the rapid spread of COVID-19, countries have asked their citizens to stay at home. As a result, demographic and cultural factors related to home life became especially relevant to predicting population well-being during isolation. This pre-registered worldwide study analyses the relationship between the number of adults and children in a household, marital status, age, gender, individualism-collectivism and perceived stress. We used the COVIDiSTRESS Global Survey data of 54,245 online participants from 27 countries. The data was collected worldwide between March 30 and April 6, 2020. Our results provide evidence that higher levels of stress are associated with younger age, being a woman, being single, staying with more children, and living in collectivistic cultures. We discuss our findings by emphasizing the need for the public health to focus on both physical and psychological well-being of these groups, as they may be especially susceptible to experiencing elevated levels of stress.
- In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries -
The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., “If you do not practice these steps, you can endanger yourself and others”) or potential gains (e.g., “If you practice these steps, you can protect yourself and others”)? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
- A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic -
Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
- A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic -
The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
- Can Information about Pandemics Increase Negative Attitudes toward Foreign Groups? A Case of COVID-19 Outbreak -
Pathogen threat can translate into a willingness to distance oneself from others on a psychological level. Building on this notion, we predicted that the ongoing coronavirus pandemic can affect attitudes toward foreign nationalities. We explored the intergroup consequences of the current epidemiological situation in two studies involving a total of 652 participants. In correlational Study 1, we showed a positive relationship between media exposure in the United Kingdom (UK) and in Poland, and prejudice to four foreign nationalities. Study 2 showed that negative affect toward Italians (i.e., a nation struggling with the most severe COVID-19 outbreak at the time of the study) was indirectly predicted by exposure to news about coronavirus through the increase in anxiety, but this effect was not observed when a generalized measure of prejudice was considered. Overall, our studies revealed that prejudice and anxiety are sensitive to the current epidemiological situation, and our findings suggest that the outbreak of COVID-19 may translate into severe social consequences and increased psychological distancing to nations most affected by the pandemic.
- Stress and worry in the 2020 coronavirus pandemic: Relationships to trust and compliance with preventive measures across 48 countries in the COVIDiSTRESS global survey -
The COVIDiSTRESS global survey collects data on early human responses to the 2020 COVID-19 pandemic from 173,429 respondents in 48 countries. The open science study was co-designed by an international consortium of researchers to investigate how psychological responses differ across countries and cultures, and how this has impacted behaviour, coping and trust in government efforts to slow the spread of the virus. Starting in March 2020, COVIDiSTRESS leveraged the convenience of unpaid online recruitment to generate public data. The objective of the present analysis is to understand relationships between psychological responses in the early months of global coronavirus resreictions, and help understand how different government measures succeed or fail in changing public behaviour. There were variations between and within countries. Although Western Europeans registered as more concerned over COVID-19, more stressed, and having slightly more trust in the governments’ efforts, there was no clear geographical pattern in compliance with behavioural measures. Detailed plots illustrating between-countries differences are provided. Using both traditional and Bayesian analyses, we found that individuals who worried about getting sick worked harder to protect themselves and others. However, concern about the coronavirus itself did not account for all of the variance in experienced stress during the early months of coronavirus restrictions. More alarmingly, such stress was associated with less compliance. Further, those most concerned over the coronavirus trusted in government measures primarily where policies were strict. While concern over a disease is a source of mental distress, other factors including strictness of protective measures, social support, and personal lockdown conditions must also be taken into consideration to fully appreciate the psychological impact of COVID-19 and to understand why some people fail to follow behavioral guidelines intended to protect themselves and others from infection.
- A Technological View of Artificial Intelligence in US Healthcare -
Since the onset of COVID-19 in the United States, hospitals became increasingly burned out—nurses reported higher levels of stress, exhaustion, and a depressive mood (Zerbini 20). Patients flooded operating rooms, ventilators were in high-demand and medical professionals worked long hours. The use of Artificial Intelligence (AI) has made a large difference. Artificial Intelligence, as defined by leading technology company IBM, is a field that combines computer science and robust datasets to enable problem-solving to make predictions or classifications (19). A researcher from the University College London and the Lancet Digital Health found that as a result, AI usage in healthcare has significantly reduced the burden on medical professionals (McCall 20). Founder of the Dutch digital health company, Sonohaler, Dr. Bohr explains that Artificial Intelligence is increasingly being used in healthcare and is expected to cut healthcare costs by 150 billion dollars by 2026. In addition, it is forecasted that the AI-healthcare market is expected to grow to 6.6 billion dollars (20). However, there are risks and drawbacks. From the University of Cambridge, in the United Kingdom, Dr. Hamid explains that AI in healthcare offers various risks and opportunities (18). As artificial intelligence is utilized at a higher frequency in the healthcare industry, it’s important to make considerations regarding its effectiveness and its future implementation. While AI in the US healthcare industry can pose potential cybersecurity risks, it serves as an important technological advancement for improving patient care such as monitoring diabetes and improving patient experience but important considerations should be made regarding the safe utilization, patient opinion, and development of artificial intelligence as it is used more in healthcare.
- Healthcare system barriers impacting the care of Canadians with myalgic encephalomyelitis: a scoping review -
Background: Myalgic encephalomyelitis (ME, also known as chronic fatigue syndrome or ME/CFS) is a debilitating, complex, multi-system illness. Developing a comprehensive understanding of the multiple and interconnected barriers to optimal care will help advance strategies and care models to improve quality of life for people living with ME in Canada. Objectives: To: (1) identify and systematically map the available evidence; (2) investigate the design and conduct of research; (3) identify and categorize key characteristics; and (4) identify and analyze knowledge gaps related to healthcare system barriers for people living with ME in Canada. Methods: The protocol was preregistered in July 2022. Peer-reviewed and grey literature was searched, and patient partners retrieved additional records. Eligible records were Canadian, included people with ME/CFS and included data or synthesis relevant to healthcare system barriers. Results: In total, 1821 records were identified, 406 were reviewed in full, and 21 were included. Healthcare system barriers arose from an underlying lack of consensus and research on ME and ME care; the impact of long-standing stigma, disbelief, and sexism; inadequate or inconsistent healthcare provider education and training on ME; and the heterogeneity of care coordinated by family physicians. Conclusions: People living with ME in Canada face significant barriers to care, though this has received relatively limited attention. This synthesis, which points to several areas for future research, can be used as a starting point for researchers, healthcare providers and decision-makers who are new to the area or encountering ME more frequently due to the COVID-19 pandemic.
- Clinical Features and Vaccine Efficacy Analysis of COVID-19 patients in a Chongqing Shelter hospital in 2022 -
Background: The long term impact of coronavirus disease 2019 (COVID19) on many aspects of society emphasizes the necessity of vaccination and nucleic acid conversion time as markers of prevention and diagnosis. However, little research has been conducted on the immunological effects of vaccines and the influencing factors of virus clearance. Epidemiological characteristics and factors related to disease prognosis and nucleic acid conversion time need to be explored. Design and participants: We reviewed published documentation to create an initial draft. The data were then statistically evaluated to determine their link. Given that a Chongqing shelter hospital is typical in terms of COVID-19 patients receiving hospital management and treatment effects, a retrospective analysis was conducted on 4,557 cases of COVID19 infection in a shelter hospital in Chongqing in December 2022, which comprised 2,291 males and 2,266 females. The variables included age, medical history, nucleic acid conversion time, vaccination status, and clinical symptoms. Results: Univariate survival analysis using the Log-rank test (P < 0.05) showed that factors such as age significantly affected nucleic acid conversion time. COX regression analysis indicated a significant association between a history of hypertension and nucleic acid conversion time, which had a hazard ratio of 0.897 (95% CI: 0.811 to 0.992). A statistically significant difference was observed between vaccinated and unvaccinated infected individuals in terms of the presence of symptoms such as cough and sensory system manifestations (P < 0.05). Conclusion: The effect of vaccination against COVID19 on symptoms such as coughing, nasal congestion, muscle aches, runny nose, and sensory system symptoms in COVID19 patients was determined. Typical symptoms, such as runny nose, were generally higher in vaccinated than in unvaccinated ones; previous hypertension was an influential factor in nucleic acid conversion time in patients with COVID19 infection.
- Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelial cells -
Respiratory syncytial virus (RSV) can cause severe disease especially in infants; however, mechanisms of age-associated disease severity remain elusive. Here, employing human bronchial epithelium models generated from tracheal aspirate-derived basal stem cells of neonates and adults, we investigated whether age regulates RSV epithelium interaction to determine disease severity. We show that following RSV infection, only neonatal epithelium model exhibited cytopathy and mucus hyperplasia, and neonatal epithelium had more robust viral spread and inflammatory responses than adult epithelium. Mechanistically, RSV-infected neonatal ciliated cells displayed age-related impairment of STAT3 activation, rendering susceptibility to apoptosis, which facilitated viral spread. In contrast, SARS-CoV-2 infection of ciliated cells had no effect on STAT3 activation and was not affected by age. Taken together, our findings identify an age-related and RSV-specific interaction with neonatal bronchial epithelium that critically contributes to severity of infection, and STAT3 activation offers a potential strategy to battle severe RSV disease in infants.
- “Yeah, this graph doesn’t show that”: Analysis of Online Engagement with Misleading Data Visualizations -
Attempting to make sense of a phenomenon or crisis, social media users often share data visualizations and interpretations that can be erroneous or misleading. Prior work has studied how data visualizations can mislead, but do misleading visualizations reach a broad social media audience? And if so, do users amplify or challenge misleading interpretations? To answer these questions, we conducted a mixed-methods analysis of the public’s engagement with data visualization posts about COVID-19 on Twitter. Compared to posts with accurate visual insights, our results show that posts with misleading visualizations garner more replies in which the audiences point out nuanced fallacies and caveats in data interpretations. Based on the results of our thematic analysis of engagement, we identify and discuss important opportunities and limitations to effectively leveraging crowdsourced assessments to address data-driven misinformation.
- COVID-19 VACCINE ACCEPTANCE AND HESITANCY IN GHANA: A SYSTEMATIC REVIEW -
The propensity to accept vaccines and factors that affect vaccine acceptance and hesitancy will determine the overall success of the COVID-19 vaccination program. Therefore, it is essential for countries to understand the factors that influence vaccine acceptance and hesitancy in order to prevent further future shocks, and it is necessary to have a thorough understanding of these factors. This study, as a result, aims to review selected published works in the domain of study and conduct valuable analysis to determine the most influential factors in COVID-19 vaccine acceptance and hesitancy in Ghana. The review also explored the acceptance rate of COVID-19 vaccines in Ghana. We selected published works from 2021 to April 2023 and extracted, analyzed, and summarized the findings based on the key factors that influence COVID-19 vaccine acceptance and hesitancy in Ghana, the acceptance rate in Ghana, the demographic factors that are often examined, and the study approach used to examine these factors. The study found that positive vaccination perception, safety, belief in vaccine efficacy, knowledge of COVID-19, and a good vaccine attitude influence COVID-19 vaccine acceptance in Ghana. The negative side effects of the vaccines, mistrust in the vaccine, lack of confidence in the safety of the vaccines, fear, and spiritual and religious beliefs all played significant roles in the factors influencing COVID-19 vaccine hesitancy. The demographic parameters frequently included in these studies that have a significant impact include educational attainment, gender, religious affiliation, age, and marital status.
- Religious People View Both Science and Religion as Less Epistemically Valuable Than Non-Religious People View Science -
Religious people typically report low perceived conflict between science and religion, but also less trust in science than non-religious people. We address these puzzling findings using insights from goal systems theory. Goal systems theory suggests that, when people have more means of achieving a goal, they perceive each individual means as less instrumental. We translate this “instrumentality hypothesis” to differences in how religious and non-religious people perceive science and religion. Religious people—who use both science and religion as means to gain knowledge—may perceive both as moderately instrumental, and as less instrumental than non-religious people, who do not use religion as a source of knowledge. We support the instrumentality hypothesis in studies where participants evaluate the capacity of science and religion to explain extraordinary phenomena (Study 1), fill gaps in knowledge (Study 2), answer life’s big questions (Study 3), and to help avoid COVID-19 infection (Study 4). We also find that non-religious people overperceive religious people’s trust in religion and underperceive religious people’s trust in science as sources of knowledge (Study 5). Our studies suggest that non-religious people think that religion specifically deters trust in science, but instead, religious people typically avoid extreme epistemic reliance on any single source of knowledge.
- COVID-19 ORF3a Viroporin Influenced Common and Unique Cellular Signalling Cascades in Lung, Heart and Brain Choroid Plexus Organoids with Additional Enriched MicroRNA Network Analyses for Lung and Brain Tissues -
Tissue specific implications of SARS-CoV-2 encoded accessory proteins are not fully understood. SARS-CoV-2 infection can severely affect three major organs - the heart, lung, and brain. We analysed SARS-CoV-2 ORF3a interacting host proteins in these three major organs. Further we identified common and unique interacting host proteins, their targeting miRNAs (lung and brain), and delineated associated biological processes reanalysing RNA-seq data from the brain (COVID-19 infected/uninfected Choroid Plexus Organoids study), lung tissue from COVID-19 patients/healthy subjects, and cardiomyocyte cells based transcriptomics analyses. Our in silico studies showed ORF3a interacting proteins could vary depending upon tissues. Number of unique ORF3a interacting proteins in brain, lung and heart were 10, 7 and 1 respectively. Though common pathways influenced by SARS-CoV-2 infection were more, unique 21 brain and 7 heart pathways were found. One unique pathway for heart was negative regulation of calcium ion transport. Reported observations of COVID-19 patients with the history of hypertension taking calcium channel blockers (CCBs) or dihydorpyridine CCBs had elevated rate of intubation or increased rate of intubation/death respectively. Also likelihood of hospitalization of chronic CCB users with COVID-19 was more in comparison to long term Angiotensin Converting Enzyme inhibitors/Angiotensin Receptor Blockers users. Further studies are necessary to confirm this. miRNA analysis of ORF3a interacting proteins in brain and lung revealed, 2 of 37 brain miRNAs and 1 of 25 lung miRNAs with high degree and betweenness indicating their significance as hubs in the interaction network. Our study could help in identifying potential tissue specific COVID-19 drug/drug repurposing targets.
- Characteristics and functions of infection-enhancing antibodies to the N-terminal domain of SARS-CoV-2 -
Characterization of functional antibody responses to the N-terminal domain (NTD) of the SARS-CoV-2 spike (S) protein has included identification of both potent neutralizing activity and putative enhancement of infection. Fc{gamma}-receptor (Fc{gamma}R)-independent enhancement of SARS-CoV-2 infection mediated by NTD-binding monoclonal antibodies (mAbs) has been observed in vitro, but the functional significance of these antibodies in vivo is not clear. Here we studied 1,213 S-binding mAbs derived from longitudinal sampling of B-cells collected from eight COVID-19 convalescent patients and identified 72 (5.9%) mAbs that enhanced infection in a VSV-SARS-CoV-2-S-Wuhan pseudovirus (PV) assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least five months post-infection. Enhancement of PV infection by NTD-binding mAbs was not observed using intestinal (Caco-2) and respiratory (Calu-3) epithelial cells as infection targets and was diminished or lost against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire from two of the convalescent subjects identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum (i.e., functionally secreted antibody). Functional analysis of these mAbs demonstrated robust activation of Fc{gamma}RIIIa associated with antibody binding to recombinant S proteins. Taken together, these findings suggest functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display diverse attributes that include Fc{gamma}R activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin) - Condition: Covid19
Interventions: Other: Placebo; Drug: Metformin
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Recruiting
Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom - Condition: Post-COVID-19 Syndrome
Interventions: Behavioral: Exercise Therapy; Behavioral: Psychotherapy
Sponsors: Hannover Medical School; Health Insurance Audi BKK; occupational health service Volkswagen AG; Helmholtz Centre for Infection Research
Not yet recruiting
A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19 - Condition: COVID-19
Interventions: Drug: HH-120; Drug: placebo
Sponsor: Huahui Health
Completed
A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2 - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: VYD222; Drug: Normal saline
Sponsor: Invivyd, Inc.
Recruiting
Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial - Condition: COVID-19
Interventions: Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells); Biological: Placebo
Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention
Not yet recruiting
Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents - Conditions: Vaccine-Preventable Diseases; COVID-19 Pandemic; Health-Related Behavior; Health Knowledge, Attitudes, Practice; Narration
Interventions: Behavioral: Baseline surveys; Behavioral: Digital Storytelling Intervention; Behavioral: Information Control Intervention
Sponsors: Arizona State University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not yet recruiting
Non-pharmacological and TCM-based Treatment for Long COVID Symptoms - Condition: Long Covid19
Intervention: Behavioral: Acupuncture and TCM-based lifestyle management
Sponsor: The Hong Kong Polytechnic University
Not yet recruiting
Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203) - Conditions: COVID-19 Infection; COVID-19 Vaccine Adverse Reaction
Interventions: Biological: LEM-mR203; Biological: Placebo
Sponsor: Lemonex
Not yet recruiting
SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People - Condition: COVID-19
Intervention: Drug: SA55 nasal spray
Sponsor: Sinovac Life Sciences Co., Ltd.
Recruiting
A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects - Condition: COVID-19
Intervention: Drug: STI-1558
Sponsor: Zhejiang ACEA Pharmaceutical Co. Ltd.
Not yet recruiting
A Study to Determine the Tolerability of Intranasal LMN-301 - Condition: COVID-19
Intervention: Biological: LMN-301
Sponsor: Lumen Bioscience, Inc.
Not yet recruiting
Mind Body Intervention for Long COVID - Conditions: Long COVID; Post-Acute Sequelae of COVID-19; COVID Long-Haul
Intervention: Behavioral: Mind Body Intervention #1
Sponsor: Beth Israel Deaconess Medical Center
Not yet recruiting
Impact of Covid-19 Aerosol Box On Intubation Success Rate - Condition: Intubation; Difficult or Failed
Interventions: Device: Intubation using aerosol box; Device: Intubation without aerosol box
Sponsor: Universiti Kebangsaan Malaysia Medical Centre
Completed
Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children - Conditions: Fever After Vaccination; Fever; Seizures Fever
Interventions: Biological: Pfizer-BioNTech COVID-19 Vaccine; Biological: Routine Childhood Vaccinations
Sponsors: Duke University; Kaiser Permanente; Columbia University; Children’s Hospital Medical Center, Cincinnati; Centers for Disease Control and Prevention
Not yet recruiting
SA55 Injection Phase II Study in the Treatment of Mild/Moderate COVID-19 Patients - Condition: Infection of Upper Respiratory Tract Caused by 2019-nCoV
Intervention: Drug: SA55 Injection
Sponsor: Sinovac Life Sciences Co., Ltd.
Recruiting
Therapeutic benefits of prophetic medicine remedies in treating hematological diseases (A review article) - Hematological disorders are common medical ailments constituting an important cause of morbidity and mortality worldwide, which may be managed efficiently using different prophetic medicine remedies as adjuvants to current therapeutics. Prophetic medicine includes the body of knowledge about medicine that has been derived from the deeds, customs (sunnah), ahadith (sayings), actions, and agreements of Prophet Muhammad, peace be upon him. This review article aims at exploring the magnitude of…
The binding mechanism of failed, in processing and succeed inhibitors target SARS-CoV-2 main protease - Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several variants have caused a persistent pandemic. Consequently, it is crucial to develop new potential anti-SARS-CoV-2 drugs with specificity. To minimize potential failures and preserve valuable clinical resources for the development of other useful drugs, researchers must enhance their understanding of the interactions between drugs and SARS-CoV-2. While numerous crystal structures of the SARS-CoV-2 main…
Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study - CONCLUSIONS: The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.
A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir - During the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage of SARS-CoV-2 infection has been a priority for controlling COVID-19. Although Paxlovid and molnupiravir have received emergency approval from the FDA, some side effect concerns have emerged, and the possible oral agents are still limited, resulting in optimized drug development becoming an urgent requirement. An oral remdesivir derivative, VV116, has been reported to have…
Identification of γ-Fagarine as a novel antiviral agent against respiratory virus (hMPV) infection - Human metapneumovirus (hMPV) causes significant upper and lower respiratory disease in all age groups worldwide. However, there is no licensed drugs or vaccine available against hMPV. γ-Fagarine, an alkaloida isolated from the root of zanthoxylum, has been reported to be effective in the treatment of cancer, inflammatory diseases and antivirals. However, little is known about the inhibitory effect of γ-Fagarine against respiratory virus infection and the mechanism. In this study, we aim to…
Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses - All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most distantly related member to SARS-CoV-2, and the mechanism for host translation inhibition by MERS-CoV Nsp1 remains controversial. Herein, we show that MERS-CoV Nsp1 directly interacts with the 40S ribosomal subunit. Using cryogenic electron microscopy (cryo-EM), we report a 2.6-Å structure of the…
Simultaneous Targeting of IL-1-Signaling and IL-6-Trans-Signaling Preserves Human Pulmonary Endothelial Barrier Function During a Cytokine Storm - CONCLUSIONS: These findings strongly suggest a major role for both IL-6 trans-signaling and IL-1β signaling in the pathological increase in permeability of the human lung microvasculature and reveal combinatorial strategies that enable the gradual control of pulmonary endothelial barrier function in response to a cytokine storm.
SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression - Viruses use microRNAs (miRNAs) to impair the host antiviral response and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. miRNAs inhibit translation initiation of their target mRNAs by recruiting the GIGYF2/4EHP translation repressor complex to the mRNA 5´-cap structure. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for…
De novo design of a stapled peptide targeting SARS-CoV-2 spike protein receptor-binding domain - Although effective vaccines have been developed against SARS-CoV-2, many regions in the world still have low rates of vaccination and new variants with mutations in the viral spike protein have reduced the effectiveness of most available vaccines and treatments. There is an urgent need for a drug to cure this disease and prevent infection. The SARS-CoV-2 virus enters the host cell through protein-protein interaction between the virus’s spike protein and the host’s angiotensin converting enzyme…
Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers - An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT(50) values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential…
Responses of patients with cancer to mRNA vaccines depend on the time interval between vaccination and last treatment - CONCLUSION: Accordingly, our data support that timing of mRNA-based therapy is critical and we suggest that at least a 6-months or 12-months waiting interval should be observed before mRNA vaccination in systemically treated patients.
Discovery of a Druggable, Cryptic Pocket in SARS-CoV-2 nsp16 Using Allosteric Inhibitors - A collaborative, open-science team undertook discovery of novel small molecule inhibitors of the SARS-CoV-2 nsp16-nsp10 2’-O-methyltransferase using a high throughput screening approach with the potential to reveal new inhibition strategies. This screen yielded compound 5a, a ligand possessing an electron-deficient double bond, as an inhibitor of SARS-CoV-2 nsp16 activity. Surprisingly, X-ray crystal structures revealed that 5a covalently binds within a previously unrecognized cryptic pocket…
Cinnamaldehyde inhibits cytokine storms induced by the ORF3a protein of SARS-CoV-2 via ROS-elimination in activated T cells - Cytokine storms are the cause of complications in patients with severe COVID-19, and it becomes the target of therapy. Several natural compounds were selected to screen the inhibitory effect on T-cell proliferation by Fluorescence-Activated Cell Sorting (FACS) and cytokine production by enzyme-linked immunosorbent assay (ELISA). Open reading frame 3a (ORF3a) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the specific T-cell activation model in vivo and in vitro. The…
How does the Immunological System Change during the SARS-COV-2 Attack? A Clue for the New Immunotherapy Discovery - The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) is one of the biggest unsolved global problems of the 21st century for which there has been no definitive cure yet. Like other respiratory viruses, SARS-COV-2 triggers the host immunity dramatically, causing dysfunction in the immune system, both innate and adaptive, which is a common feature of COVID-19 patients. Evidence shows that in the early stages of COVID-19, the immune system is suppressed…
Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection - TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to…