Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• A mechanism that transduces lysosomal damage signals to stress granule formation for cell survival -
  Lysosomal damage poses a significant threat to cell survival. Our previous work has reported that lysosomal damage induces stress granule (SG) formation. However, the importance of SG formation in determining cell fate and the precise mechanisms through which lysosomal damage triggers SG formation remains unclear. Here, we show that SG formation is initiated via a novel calcium-dependent pathway and plays a protective role in promoting cell survival in response to lysosomal damage. Mechanistically, we demonstrate that during lysosomal damage, ALIX, a calcium-activated protein, transduces lysosomal damage signals by sensing calcium leakage to induce SG formation by controlling the phosphorylation of eIF2. ALIX modulates eIF2 phosphorylation by regulating the association between PKR and its activator PACT, with galectin-3 exerting a negative effect on this process. We also found this regulatory event of SG formation occur on damaged lysosomes. Collectively, these investigations reveal novel insights into the precise regulation of SG formation triggered by lysosomal damage, and shed light on the interaction between damaged lysosomes and SGs. Importantly, SG formation is significant for promoting cell survival in the physiological context of lysosomal damage inflicted by SARS-CoV-2 ORF3a, adenovirus infection, Malaria hemozoin, proteopathic tau as well as environmental hazard silica.
  🖺 Full Text HTML: A mechanism that transduces lysosomal damage signals to stress granule formation for cell survival
• Aversive personality and COVID-19: A first review and meta-analysis -
  The Coronavirus Disease 2019 (COVID-19) has strongly affected individuals and societies worldwide. In this review and meta-analysis, we investigated how aversive personality traits—i.e., relatively stable antisocial personality characteristics—related to how individuals perceived, evaluated, and responded to the COVID-19 pandemic. Across 34 studies with overall 26,780 participants, we found that people with higher scores in aversive personality traits were less likely to perceive guidelines and restrictions to curb the spread of the virus as protective (p̂ = -.11), to engage in health behaviors related to COVID-19 (p̂ = -.16), and to engage in non-health related prosocial behavior related to COVID-19 (p̂ = -.14). We found no consistent relation between aversive personality and negative affect regarding the pandemic. The results thus indicate the importance of aversive personality traits in understanding individual differences with regard to COVID-19.
  🖺 Full Text HTML: Aversive personality and COVID-19: A first review and meta-analysis
• Information about herd immunity through vaccination and empathy promote COVID-19 vaccination intentions -
  Objective: An effective vaccine against COVID-19 is a desired solution to curb the spread of the disease. However, vaccine hesitancy might hinder high uptake rates and thus undermine efforts to eliminate COVID-19 once an effective vaccine became available. The present contribution addresses this issue by examining two ways of increasing the intention to get vaccinated against COVID-19. Methods: Two pre-registered online studies were conducted (N = 2,315 participants from the UK) in which knowledge about and beliefs in herd immunity through vaccination, as well as empathy for those most vulnerable to the virus, were either measured (Study 1) or manipulated (Study 2). As a dependent variable, individuals’ self-reported vaccination intention once a vaccine against COVID-19 became available was assessed. Results: In Study 1 (N = 310), the intention to get vaccinated against COVID-19 was correlated with knowledge about and belief in herd immunity (r = .58, p < .001), as well as with empathy for those most vulnerable to the virus (r = .26, p < .001). In Study 2 (N = 2,005), information about herd immunity (Cohen’s d = 0.13, p = .003) and empathy (Cohen’s d = 0.22, p < .001) independently promoted vaccination intention. Conclusions: The motivation to get vaccinated against COVID-19 was related to and could be causally promoted by both mere information about herd immunity and by empathy. As such, the present research provides a better understanding of the intention to get vaccinated against COVID-19.
  🖺 Full Text HTML: Information about herd immunity through vaccination and empathy promote COVID-19 vaccination intentions
• The emotional path to action: Empathy promotes physical distancing and wearing of face masks during the COVID-19 pandemic -
  The COVID-19 pandemic presents a major challenge to societies all over the globe. To curb the spread of the disease, two measures implemented in many countries are minimizing close contact between people (“physical distancing”) and wearing face masks. In the present research, we tested the idea that physical distancing and wearing face masks can be the result of a genuine prosocial emotion—empathy for those most vulnerable to the virus. In four pre-registered studies (total N = 3,718‬, Western population), we show that (i) empathy is indeed a basic motivation for physical distancing and wearing face masks, and (ii) inducing empathy for those most vulnerable to the virus promotes the motivation to adhere to these measures (whereas providing mere information about its importance is not). In sum, the present research provides a better understanding of the promoting factors underlying the willingness to follow two important measures during the COVID-19 pandemic.
  🖺 Full Text HTML: The emotional path to action: Empathy promotes physical distancing and wearing of face masks during the COVID-19 pandemic
• Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: Implications to alternative conformations and their statistical structural analyses -
  The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge. Here, we show by DMS and dual-luciferase functional assays that previously predicted FSE mutants (using the RAG graph theory approach) suppress structural transitions and abolish frameshifting. Furthermore, correlated mutation analysis of DMS data by three programs (DREEM, DRACO, and DANCE-MaP) reveals important differences in their estimation of specific RNA conformations, suggesting caution in the interpretation of such complex conformational landscapes. Overall, the abolished frameshifting in three different mutants confirms that all alternative conformations play a role in the pathways of ribosomal transition.
  🖺 Full Text HTML: Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: Implications to alternative conformations and their statistical structural analyses
• Broad-Spectrum Coronavirus Inhibitors Discovered by Modeling Viral Fusion Dynamics -
  Broad-spectrum therapeutics capable of inhibiting SARS-CoV-2, its variants, and related coronaviruses hold promise in curbing the spread of COVID-19 and averting future pandemics. Here, we employed a multidisciplinary approach that included molecular dynamics simulation (MDS) and artificial intelligence (AI)-based docking predictions to identify potent inhibitors that target a conserved region within the SARS-CoV-2 spike protein that mediates membrane fusion by undergoing large-scale mechanical rearrangements. In silico binding screens honed in on this region, leading to the discovery of FDA-approved drugs and novel molecules predicted to disrupt spike protein conformational changes. These compounds significantly inhibited SARS-CoV-2 infection and blocked the entry of spike protein-bearing pseudotyped , {beta}, {gamma}, {delta} variants as well as SARS-CoV and MERS-CoV in cultured human ACE2-expressing cells. The optimized lead compound significantly inhibited SARS-CoV2 infection in mice when administered orally.
  🖺 Full Text HTML: Broad-Spectrum Coronavirus Inhibitors Discovered by Modeling Viral Fusion Dynamics
• Enhanced mucosal B- and T-cell responses against SARS-CoV-2 after heterologous intramuscular mRNA prime/intranasal protein boost vaccination with a combination adjuvant. -
  Current COVID-19 mRNA vaccines delivered intramuscularly (IM) induce effective systemic immunity, but with suboptimal immunity at mucosal sites, limiting their ability to impart sterilizing immunity. There is strong interest in rerouting immune responses induced in the periphery by parenteral vaccination to the portal entry site of respiratory viruses, such as SARS-CoV-2, by mucosal vaccination. We previously demonstrated the combination adjuvant, NE/IVT, consisting of a nanoemulsion (NE) and an RNA-based RIG-I agonist (IVT) induces potent systemic and mucosal immune responses in protein-based SARS-CoV-2 vaccines administered intranasally (IN). Herein, we demonstrate priming IM with mRNA followed by heterologous IN boosting with NE/IVT adjuvanted recombinant antigen induces strong mucosal and systemic antibody responses and enhances antigen-specific T cell responses in mucosa-draining lymph nodes compared to IM/IM and IN/IN prime/boost regimens. While all regimens induced cross-neutralizing antibodies against divergent variants and sterilizing immunity in the lungs of challenged mice, mucosal vaccination, either as homologous prime/boost or heterologous IN boost after IM mRNA prime was required to impart sterilizing immunity in the upper respiratory tract. Our data demonstrate the benefit of hybrid regimens whereby strong immune responses primed via IM vaccination are rerouted by IN vaccination to mucosal sites to provide optimal protection to SARS-CoV-2.
  🖺 Full Text HTML: Enhanced mucosal B- and T-cell responses against SARS-CoV-2 after heterologous intramuscular mRNA prime/intranasal protein boost vaccination with a combination adjuvant.
• Development and Application of Decontamination Methods for the Re-Use of Laboratory Grade Plastic Pipette Tips -
  During the SARS-CoV-2 pandemic, a need for methods to decontaminate and reuse personal protective equipment (PPE) and medical plastics became a priority. In this investigation we aimed to develop a contamination evaluation protocol for laboratory pipette tips, after decontamination. Decontamination methods tested in this study included cleaning with a common laboratory detergent (2.5% Alconox(R) solution followed with steam decontamination), exposure of ozone vapor at 250 and 14400 PPM * minute, and exposure to cold atmospheric plasma (CAP). All tips (control and experimental groups) were introduced to the methods described, while tips exposed to DNA extracts of Aeromonas hydrophila (ATCC-23211) were assessed for experimental groups. Decontamination was determined by turnover ratio and log reduction in detectable genomic material on the contaminated products using real-time quantitative PCR (qPCR) assay. Our results showed, cleaning tips with lab detergents along with steam decontamination removed genetic material, resulting in the highest log reduction, compared with ozone or CAP treatments. Detergent/washing methods showed the highest turnover ratio (95.9 %) and log reduction (5.943). However, the excessive residue (post- cleaning) on the plastic, within inner filters, and tip boxes suggested that washing with lab detergents was not favorable for reuse. Ozone vapor at 14400 PPM * minutes showed the second highest turnover ratio (98.4 %) and log reduction (4.511). CAP exposure with tips inverted (the tip end exposed closer to the plasma flame) for 1 minute showed a turnover ratio of (68.3 %) and log reduction (4.002). Relatively, lower turnover ratio and log reduction of CAP could be attributed to development/optimization of treatment conditions, including increases in exposure time and relative to tip positioning.
  🖺 Full Text HTML: Development and Application of Decontamination Methods for the Re-Use of Laboratory Grade Plastic Pipette Tips
• Human long noncoding RNA, VILMIR, is induced by major respiratory viral infections and modulates the host interferon response -
  Long noncoding RNAs (lncRNAs) are a newer class of noncoding transcripts identified as key regulators of biological processes. Here we aimed to identify novel lncRNA targets that play critical roles in major human respiratory viral infections by systematically mining large-scale transcriptomic datasets. Using bulk RNA-sequencing (RNA-seq) analysis, we identified a previously uncharacterized lncRNA, named virus inducible lncRNA modulator of interferon response (VILMIR), that was consistently upregulated after in vitro influenza infection across multiple human epithelial cell lines and influenza A virus subtypes. VILMIR was also upregulated after SARS-CoV-2 and RSV infections in vitro. We experimentally confirmed the response of VILMIR to influenza infection and interferon-beta (IFN-{beta}) treatment in the A549 human epithelial cell line and found the expression of VILMIR was robustly induced by IFN-{beta} treatment in a dose and time-specific manner. Single cell RNA-seq analysis of bronchoalveolar lavage fluid (BALF) samples from COVID-19 patients uncovered that VILMIR was upregulated across various cell types including at least five immune cells. The upregulation of VILMIR in immune cells was further confirmed in the human T cell and monocyte cell lines, SUP-T1 and THP-1, after IFN-{beta} treatment. Finally, we found that knockdown of VILMIR expression reduced the magnitude of host transcriptional responses to IFN-{beta} treatment in A549 cells. Together, our results show that VILMIR is a novel interferon-stimulated gene (ISG) that regulates the host interferon response and may be a potential therapeutic target for human respiratory viral infections upon further mechanistic investigation.
  🖺 Full Text HTML: Human long noncoding RNA, VILMIR, is induced by major respiratory viral infections and modulates the host interferon response
• Inference of epidemic dynamics in the COVID-19 era and beyond -
  The COVID-19 pandemic demonstrated the key role that epidemiology and modelling play in analysing infectious threats and supporting decision making in real-time. Motivated by the unprecedented volume and breadth of data generated during the pandemic, we review new analytic opportunities and methodological developments available to address questions that emerge during a major modern epidemic. Following the broad chronology of insights required - from understanding initial dynamics to retrospective evaluation of interventions, we describe the theoretical foundations of each approach and the underlying intuition. Through a series of case studies, we illustrate real life applications, and discuss implications for future work.
  🖺 Full Text HTML: Inference of epidemic dynamics in the COVID-19 era and beyond
• A qualitative exploration of triggers for alcohol use and access to alcohol services during the COVID-19 pandemic among people identifying as problem drinkers. -
  Introduction A polarisation of drinking behaviour was observed during the COVID-19 pandemic with some people reported to be drinking more alcohol and others less. We aimed to understand how and why the COVID-19 pandemic and associated restrictions impacted alcohol use and access to support and services during this time. Methods We conducted semi-structured qualitative interviews with 27 participants, including 20 people identifying as problem drinkers and seven alcohol service providers. Data were analysed using reflexive thematic analysis. Results We identified two main triggers for alcohol use during the pandemic: i) loss of daily routine and activity resulted in drinking to cope with social isolation and boredom and ii) drinking alleviated feelings of fear, anxiety and anger over the imposition of pandemic restrictions. Regarding access to services, two main themes were generated: i) remote service provision was perceived as inferior to in-person services and ii) the need to offer choice and flexibility in how services were provided, with service providers reporting more positive experiences of online and telephone service delivery than service users. Discussion and Conclusions This study provides new insights into potential triggers for alcohol use among people identifying as problem drinkers during the COVID-19 pandemic. The acceptability of remote forms of service provision were dependent on service user access to and comfort with using technology. Hybrid delivery models may therefore be suitable in some but not all circumstances, and efforts should be made to promote equitable access to services.
  🖺 Full Text HTML: A qualitative exploration of triggers for alcohol use and access to alcohol services during the COVID-19 pandemic among people identifying as problem drinkers.
• Does behavior mediate the effect of weather on SARS-CoV-2 transmission? Evidence from cell-phone data -

  Background: There is growing evidence that weather alters SARS-CoV-2 transmission, but it remains unclear what drives the phenomenon. One prevailing hypothesis is that people spend more time indoors in cooler weather, leading to increased spread of SARS-CoV-2 related to time spent in confined spaces and close contact with others. However, the evidence in support of that hypothesis is limited and, at times, conflicting. Objectives: We aim to evaluate the extent to which weather impacts COVID-19 via time spent away-from-home in indoor spaces, as compared to a direct effect of weather on COVID-19 hospitalization, independent of mobility. Methods: We use a mediation framework, and combine daily weather, COVID-19 hospital surveillance, cellphone-based mobility data and building footprints to estimate the relationship between daily indoor and outdoor weather conditions, mobility, and COVID-19 hospitalizations. We quantify the direct health impacts of weather on COVID-19 hospitalizations and the indirect effects of weather via time spent indoors away-from-home on COVID-19 hospitalizations within five Colorado counties between March 4th 2020 and January 31st 2021. Results: We found evidence that changes in 12-day lagged hospital admissions were primarily via the direct effects of weather conditions, rather than via indirect effects by which weather changes time spent indoors away-from-home. Sensitivity analyses evaluating time at home as a mediator were consistent with these conclusions. Discussion: Our findings do not support the hypothesis that weather impacted SARS-CoV-2 transmission via changes in mobility patterns during the first year of the pandemic. Rather, weather appears to have impacted SARS-CoV-2 transmission primarily via mechanisms other than human movement. We recommend further analysis of this phenomenon to determine whether these findings generalize to current SARS-CoV-2 transmission dynamics and other seasonal respiratory pathogens.

  🖺 Full Text HTML: Does behavior mediate the effect of weather on SARS-CoV-2 transmission? Evidence from cell-phone data
• Strengthening access to and confidence in COVID-19 vaccines among equity-deserving populations across Canada: An exploratory qualitative study -

  Introduction: There is a need to reflect on the COVID-19 vaccine distribution across Canada and the extent to which they considered equity-deserving populations. This paper examined and compared strategies implemented by six Canadian provinces to increase access and promote the uptake of COVID-19 vaccines among selected priority populations. We also explored the factors that impacted the implementation of these strategies. Methods: In six provinces (Alberta, British Columbia, Manitoba, Nova Scotia, Ontario, and Quebec), we conducted an environmental scan of provincial rollout documents and media sources reporting vaccine distribution among selected priority populations:First Nations, Inuit, and Metis; Black communities; essential workers; people experiencing homelessness; and people with disabilities. We subsequently interviewed 39 key informants to validate the environmental scan results, identify additional strategies to increase COVID-19 vaccine uptake, and uncover perceptions of the facilitators and challenges that influenced the strategies’ implementation. Results: Through the environmental scans and key informant interviews, we identified that provincial health authorities employed a panoply of strategies to overcome geographic, financial, and attitudinal barriers to COVID-19 vaccines experienced by the priority populations. Most provinces implemented walk-in, mobile, and pop-up vaccination clinics, mobilized public and private health workforce, and designed multilingual communication materials. Facilitators in implementing COVID-19 vaccination strategies included fostering inter-governmental cooperation, harmonizing communication efforts, leveraging existing relationships and networks, and ensuring representation and leadership of community partners. Challenges to implementing COVID-19 vaccination strategies included uncoordinated communication efforts, inadequate distribution of vaccines to areas with the greatest need, mistrust in the government and healthcare system, vaccine hesitancy, and lack of cultural competence by vaccine providers.   Conclusions: This study highlights the divide between well-intentioned strategies and interventions and the reality of on-the-ground implementation. The findings offer valuable insights and can inform the implementation of strategies to distribute vaccines equitably in future large-scale vaccination efforts in Canada and globally.

  🖺 Full Text HTML: Strengthening access to and confidence in COVID-19 vaccines among equity-deserving populations across Canada: An exploratory qualitative study
• COHORT PROFILE: IMMUNE RESPONSES TO SARS-COV-2 VACCINATION AND INFECTION IN A LONGITUDINAL SAMPLING AMIDST THE COVID-19 PANDEMIC (LONGTONG-SARS2) IN MALAYSIA -

  Purpose: This prospective, longitudinal study aims to evaluate the durability and functionality of SARS-CoV-2 Ancestral strain (Wuhan-Hu-1)-specific immune responses induced by COVID-19 vaccination and natural infection over a 12-month period. This article reviews the study protocol, design, methodology, ongoing data collection, analysis procedures, and demographic characteristics of the cohort enrolled. Participants: Between March 2021 and May 2022, 400 participants were enrolled with a 12-month follow-up, concluding in May 2023. Two main groups of participants: (1) serologically SARS-CoV-2-naive individuals receiving the BNT162b2 primary series vaccination (referred to as VAC) and (2) those who recently recovered from COVID-19 infection within 30 days, regardless of vaccination history (referred to as COV). Additionally, a subset of 45 participants with selected COVID-19 exposure histories provided peripheral blood mononuclear cells (PBMCs) for cross-sectional analysis six months after enrollment. Findings to date: Out of 400 participants, 66.8% (n=267) completed the follow-up. Among them, 52.8% (n=141) were in VAC, and 47.2% (n=126) were in COV. As the study progressed, we acknowledged cross-over between initial groups, leading to restructuring into five revised groups based on sequential exposure events. Sociodemographic factors revealed statistically significant age distribution differences (p=0.001) in both initial and revised groups, with no significant differences observed for sex. Future plans: LONGTONG-SARS2 assesses the host-pathogen interactions central to the development of COVID-19 immunity. With enrollment spanning two years of the pandemic, most participants exhibited mixed SARS-CoV-2 exposures-via vaccination and infection-resulting in diverse subgroups of interest. Notably, the inclusion of SARS-CoV-2-naive, pre-exposure serum samples allowed for robust comparator and reduced potential biases. Ongoing analyses will include serology kinetics, memory cells ELISpots, B cells repertoire analysis, cytokine/chemokine profiling, and proteomic pathway to comprehensively examine the immune response against the SARS-CoV-2, thus informing and potentially predicting dynamic longitudinal responses against new more transmissible, immune-evasive SARS-CoV-2 variants.

  🖺 Full Text HTML: COHORT PROFILE: IMMUNE RESPONSES TO SARS-COV-2 VACCINATION AND INFECTION IN A LONGITUDINAL SAMPLING AMIDST THE COVID-19 PANDEMIC (LONGTONG-SARS2) IN MALAYSIA
• The 10-year health impact, economic impact, and return on investment of the South African molecular diagnostics programme for HIV, Tuberculosis and SARS-CoV-2 -

  To ensure there is adequate investment into diagnostics, an understanding of the magnitude of impact and return on investment is necessary. We therefore sought to understand the health and economic impacts of the molecular diagnostic programme in South Africa, to deepen the under-standing on the broad value of diagnostics and guide future healthcare investments. We calcu-lated the 10-year (where data were available) total cost and DALYs averted associated with molecular diagnosis of molecular TB testing (2013-2022), HIV viral load monitoring (2013-2022), early infant diagnosis of HIV infection (2013-2022), and SARS-CoV-2 testing (2020-2022). We then calculated the economic value associated with those health gains and subsequent return on investment. Since the inception of the molecular diagnostics programme in South Africa, 3,035,782 DALYs have been averted as a direct consequence of this pro-gramme. This has generated an estimated $20.5 billion in economic value due to these health gains. The return on investment varied by specific diagnostic test (19.0 for tuberculosis, 1.4 for HIV viral load testing, 64.8 for early infant diagnosis of HIV, and 2.5 for SARS-CoV-2), for an average of 9.9 for the entire molecular diagnostics programme between 2013 and 2022- or $9.9 of value for each $1 invested. The molecular diagnostics programme in South Africa gen-erated a significant amount of health gains and economic value associated with these health gains, and the return-on-investment rivals other high-impact public health interventions such as childhood vaccination. Consequently, the molecular diagnostics programme in South Africa is highly impactful, and will continue to be an excellent investment of South African public health expenditure.

  🖺 Full Text HTML: The 10-year health impact, economic impact, and return on investment of the South African molecular diagnostics programme for HIV, Tuberculosis and SARS-CoV-2

From Clinical Trials

• Diaphragmatic Breathing Exercises for Post-COVID-19 Diaphragmatic Dysfunction (DD) - Conditions: Post-Acute Sequelae of COVID-19
  Interventions: Other: Usual care of traditional treatment; Other: Specific DB program/Diaphragmatic manipulation program
  Sponsors: University of Minnesota
  Recruiting

• Valacyclovir Plus Celecoxib for Post-Acute Sequelae of SARS-CoV-2 - Conditions: Long COVID; PASC Post Acute Sequelae of COVID 19
  Interventions: Drug: Valacyclovir celecoxib dose 1; Drug: Valacyclovir celecoxib dose 2; Drug: Placebo
  Sponsors: Bateman Horne Center
  Recruiting

• Supervised Computerized Active Program for People With Post-COVID Syndrome (SuperCAP Study) - Conditions: Post-COVID Condition
  Interventions: Device: SuperCAP Program
  Sponsors: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; Institut de Recerca de la SIDA IrsiCaixa; Germans Trias i Pujol Hospital
  Recruiting

From PubMed

• Comparative evaluation of tocilizumab and itolizumab for treatment of severe COVID-19 in India: a retrospective cohort study - CONCLUSIONS: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

• Synthesis and pharmacodynamic evaluation of Dihydropteridone derivatives against PDCoV in vivo and in vitro - Porcine Delta Coronavirus (PDCoV) infection can induce serious dehydration, diarrhea and even death of piglets, which has caused huge losses to the breeding industry. PDCoV has been reported to have the potential for cross species transmission, and even reports of infecting humans have emerged. At present, there are still no effective prevention and control measures for PDCoV. In this study, we have designed and synthesized a series of unreported Dihydropteridone derivatives. All of these…

• New conjugates based on N4-hydroxycytidine with more potent antiviral efficacy in vitro than EIDD-2801 against SARS-CoV-2 and other human coronaviruses - The spread of COVID-19 continues due to genetic variation in SARS-CoV-2. Highly mutated variants of SARS-CoV-2 have an increased transmissibility and immune evasion. Due to the emergence of various new variants of the virus, there is an urgent need to develop broadly effective specific drugs for therapeutic strategies for the prevention and treatment of COVID-19. Molnupiravir (EIDD-2801, MK-4482), is an orally bioavailable ribonucleoside analogue of β-D-N4-hydroxycytidine (NHC), has demonstrated…

• Biological responses in Danio rerio by the disinfectant SDBS in SARS-CoV-2 pandemic - The use of disinfectants, such as Sodium Dodecylbenzene Sulfonic acid salt (SDBS), has grown since the SARS-CoV-2 pandemic, with environmentally unknown consequences. The present study analyzed SDBS effects in the fish species Danio rerio, using a combination of biomarkers. Our data reported that larvae had their total locomotor activity increased when exposed to 1mg/L of SDBS, but this parameter was decreased in fish exposed to 5mg/L. A significant increment of erratic movements was reported in…

• Preclinical evaluation of the SARS-CoV-2 M(pro) inhibitor RAY1216 shows improved pharmacokinetics compared with nirmatrelvir - Although vaccines are available for SARS-CoV-2, antiviral drugs such as nirmatrelvir are still needed, particularly for individuals in whom vaccines are less effective, such as the immunocompromised, to prevent severe COVID-19. Here we report an α-ketoamide-based peptidomimetic inhibitor of the SARS-CoV-2 main protease (M^(pro)), designated RAY1216. Enzyme inhibition kinetic analysis shows that RAY1216 has an inhibition constant of 8.4 nM and suggests that it dissociates about 12 times slower…

• A new DNA aptamer which binds to SARS-CoV-2 spike protein and reduces pro-inflammatory response - COVID-19 caused by SARS-CoV-2 spread rapidly around the world, endangering the health of people globally. The SARS-CoV-2 spike protein initiates entry into target cells by binding to human angiotensin-converting enzyme 2 (ACE2). In this study, we developed DNA aptamers that specifically bind to the SARS-CoV-2 spike protein, thereby inhibiting its binding to ACE2. DNA aptamers are small nucleic acid fragments with random structures that selectively bind to various target molecules. We identified…

• Protective mucosal SARS-CoV-2 antibodies in the majority of the general population in the Netherlands - Antibodies to SARS-CoV-2 at mucosal surfaces of the respiratory tract are understood to contribute to protection against SARS-CoV-2 infection. We aimed to describe the prevalence, levels and functionality of mucosal antibodies in the general Dutch population. Nasal samples were collected from 778 randomly selected participants, 1-90 years of age, nested within the nationwide prospective SARS-CoV-2 PIENTER corona serosurvey in the Netherlands. Spike-specific IgG was detected in nasal samples of…

• Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has decreased the efficacy of SARS-CoV-2 vaccines in containing coronavirus disease 2019 (COVID-19) over time, and booster vaccination strategies are urgently necessitated to achieve sufficient protection. Intranasal immunization can improve mucosal immunity, offering protection against the infection and sustaining the spread of SARS-CoV-2. In this study, an intranasal booster of the RBD-HR vaccine after two…

• Investigation of phytochemicals isolated from selected Saudi medicinal plants as natural inhibitors of SARS CoV-2 main protease: In vitro, molecular docking and simulation analysis - The escalation of many coronavirus variants accompanied by the lack of an effective cure has motivated the hunt for effective antiviral medicines. In this regard, 18 Saudi Arabian medicinal plants were evaluated for SARS CoV-2 main protease (Mpro) inhibition activity. Among them, Terminalia brownii and Acacia asak alcoholic extracts exhibited significant Mpro inhibition, with inhibition rates of 95.3 % and 95.2 %, respectively, at a concentration of 100 µg/mL. Bioassay-guided phytochemical study…

• Safety and immunogenicity of CoronaVac and ChAdOx1 heterologous prime-boost vaccines in an overweight population in Chiang Mai, Thailand - CONCLUSIONS: The heterologous CoronaVac-ChAdOx1vaccination was safe, well-tolerated and able to induce humoral immunity against wild-type and Delta variants but not against the Omicron variant in overweight population.

• Design of a SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model - The emergence of SARS-CoV-2 variants and drug-resistant mutants calls for additional oral antivirals. The SARS-CoV-2 papain-like protease (PL^(pro)) is a promising but challenging drug target. We designed and synthesized 85 noncovalent PL^(pro) inhibitors that bind to a recently discovered ubiquitin binding site and the known BL2 groove pocket near the S4 subsite. Leads inhibited PL^(pro) with the inhibitory constant K(i) values from 13.2 to 88.2 nanomolar. The co-crystal structures of PL^(pro)…

• On parrots, delay of gratification, executive function, and how sometimes we do the best we can - Engaging executive functions provides an individual with the means to engage in cognitive control by adjusting to the environment and processing information in a way that leads to optimal outcomes. There are some claims that explicit training on certain executive functioning abilities provides benefits beyond the training tasks, but other studies indicate that this may not be true or may be limited based on age and other factors. This same mixed pattern has been reported with nonhuman species,…

• Role for CCN1 in lysophosphatidic acid response in PC-3 human prostate cancer cells - Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are bioactive phospholipids that act as mitogens in various cancers. Both LPA and S1P activate G-protein coupled receptors (GPCRs). We examined the role of CCN1/CYR61, an inducible matricellular protein, in LPA-induced signal transduction in PC-3 human prostate cancer cells. We found that both LPA and S1P induced expression of CCN1 and CCN2 within 2-4 h. CCN1 was induced by 18:1-LPA, but not by 18:0-, 18:2-, or 18:3-LPAs. A free fatty…

• Fungal metabolite 6-pentyl-alpha-pyrone reduces canine coronavirus infection - Canine coronavirus (CCoV) can produce a self-limited enteric disease in dogs but, because of notable biological plasticity of coronaviruses (CoVs), numerous mutations as well as recombination events happen leading to the emergence of variants often more dangerous for both animals and humans. Indeed, the emergence of new canine-feline recombinant alphacoronaviruses, recently isolated from humans, highlight the cross-species transmission potential of CoVs. Consequently, new effective antiviral…

• Pilot Study on Evaluating the Impact of Tetanus, Diphtheria, and Pertussis (Tdap), Influenza, and COVID-19 Vaccinations on Antibody Responses in Pregnant Women - This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated…

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