Covid-19 Sentry

Contents

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

From Preprints

• SARS-CoV-2 lineage assignments using phylogenetic placement/UShER are superior to pangoLEARN machine learning method -
  With the rapid spread and evolution of SARS-CoV-2, the ability to monitor its transmission and distinguish among viral lineages is critical for pandemic response efforts. The most commonly used software for the lineage assignment of newly isolated SARS-CoV-2 genomes is pangolin, which offers two methods of assignment, pangoLEARN and pUShER. PangoLEARN rapidly assigns lineages using a machine learning algorithm, while pUShER performs a phylogenetic placement to identify the lineage corresponding to a newly sequenced genome. In a preliminary study, we observed that pangoLEARN (decision tree model), while substantially faster than pUShER, offered less consistency across different versions of pangolin v3. Here, we expand upon this analysis to include v3 and v4 of pangolin, which moved the default algorithm for lineage assignment from pangoLEARN in v3 to pUShER in v4, and perform a thorough analysis confirming that pUShER is not only more stable across versions but also more accurate. Our findings suggest that future lineage assignment algorithms for various pathogens should consider the value of phylogenetic placement.
  🖺 Full Text HTML: SARS-CoV-2 lineage assignments using phylogenetic placement/UShER are superior to pangoLEARN machine learning method
• The experiences of COVID-19 preprint authors: A survey of researchers about publishing and receiving feedback on their work during the pandemic -
  The COVID-19 pandemic caused a rise in preprinting, triggered by the need for open and rapid dissemination of research outputs. We surveyed authors of COVID-19 preprints to learn about their experiences with preprinting their work and also with publishing their work in a peer-reviewed journal. Our research had the following objectives: 1. to learn about authors’ experiences with preprinting, their motivations, and future intentions; 2. to consider preprints in terms of their effectiveness in enabling authors to receive feedback on their work; 3. to compare the impact of feedback on preprints with the impact of comments of editors and reviewers on papers submitted to journals. In our survey, 78% of the new adopters of preprinting reported the intention to also preprint their future work. The boost in preprinting may therefore have a structural effect that will last after the pandemic, although future developments will also depend on other factors, including the broader growth in the adoption of open science practices. 53% of the respondents reported that they had received feedback on their preprints. However, more than half of the feedback was received through “closed” channels – privately to the authors. This means that preprinting was a useful way to receive feedback on research, but the value of feedback could be increased further by facilitating and promoting “open” channels for preprint feedback. Almost a quarter of the feedback received by respondents consisted of detailed comments, showing the potential of preprint feedback to provide valuable comments on research. Respondents also reported that, compared to preprint feedback, journal peer review was more likely to lead to major changes to their work, suggesting that journal peer review provides significant added value compared to feedback received on preprints.
  🖺 Full Text HTML: The experiences of COVID-19 preprint authors: A survey of researchers about publishing and receiving feedback on their work during the pandemic
• The new normal: changed patterns of dwelling demand and supply -
  This research assessed the impact of the COVID-19 pandemic on patterns of housing supply and demand and how the Australian housing market has changed over recent time (including between the 2016 and 2021 Censuses). The pandemic showed just how quickly demand for housing can change and how prices and rents can rise rapidly as a result. The COVID-19 period, defined as mid-2020 to mid-2022 for the purposes of this study, saw robust price growth within Australian capital cities and even stronger growth in regional areas. In the rental market, vacancy rates fell across the country and rents rose sharply. COVID changed what households want from their dwelling: predominantly it was about having more space, both inside and out, and that was linked with the ability to work more from home. Overall, consumers continue to prefer houses over units in metropolitan areas. COVID-19 also created significant and distinct changes to population dynamics with low or negative growth within inner urban areas; growth in regional towns and cities, particularly those associated with sea and tree changes; and strong growth in traditional first home buyer areas, primarily on the urban periphery. Property sales in high-growth regions came significantly from investors who sold stock from the rental market (generally to first home buyers and second home buyers). This, in turn, reduced rental availability and vacancy rates and displaced private renters. Where investors did buy into the regional areas studied, these were at higher prices which were in turn reflected in higher rents. The research reiterates that increases in housing supply need to be carefully managed by governments, including the supply of social and affordable housing in regional areas.
  🖺 Full Text HTML: The new normal: changed patterns of dwelling demand and supply
• Household Hardships during the COVID-19 Pandemic: Examining Household Vulnerability and Responses to Pandemic Related Shocks in Eastern Ethiopia -

  COVID-19 is associated with one of the largest disturbances to life in the 21st century. To quell disease spread, governments implemented lockdowns that likely created hardships for house-holds. To improve knowledge of consequences, we examine how the pandemic period was associ-ated with household hardships and assess factors associated with these hardships. We conducted a cross-sectional study using quasi-Poisson regression to examine factors associated with house-hold hardships. Data were collected between August and September of 2021 from a random sam-ple of 880 households living in a Health and Demographic Surveillance System (HDSS) located in the Harari Region and the District of Kersa, both in Ethiopia. Having a head of household with no education, residing in a rural area, larger household size, lower income and/or wealth, and community responses to COVID-19 including lockdowns and travel restrictions were inde-pendently associated with experiencing household hardships. Our results identify characteristics of groups at-risk for food insecurity during the pan-demic; households that were already strug-gling prior to the onset of the pandemic were at greatest risk of adverse consequences during the pandemic period. These findings may inform future efforts to mitigate the consequences of COVID-19 and future disease out-breaks.

  🖺 Full Text HTML: Household Hardships during the COVID-19 Pandemic: Examining Household Vulnerability and Responses to Pandemic Related Shocks in Eastern Ethiopia
• Food Insecurity amid COVID-19 Lockdowns: Assessing Sociodemographic Indicators of Vulnerability in Harar and Kersa, Ethiopia -

  Objective The COVID-19 pandemic was associated with widespread social disruptions, as governments implemented lockdowns to quell disease spread. To advance knowledge of consequences for households in lower-income countries, we examine food insecurity during the pandemic period. Design Cross-sectional study using logistic regression to examine factors associated with food insecurity. Data were collected between August and September of 2021 through a Health and Demographic Surveillance System (HDSS) using a survey instrument focused on knowledge regarding the spread of COVID-19; food availability; COVID-19 related shocks/coping; under-five child healthcare services; and healthcare services for pregnant women. Setting The study is set in two communities in Eastern Ethiopia, one rural and one urban. Participants A random sample of 880 households residing in Kersa and Harar. Results Roughly 16% of households reported not having enough food to eat during the pandemic, an increase of 6% since before the pandemic. After adjusting for other variables, households were more likely to report food insecurity if they were living in an urban area, were a larger household, had a family member lose employment, reported an increase in food prices, or were food insecure before the pandemic. Households were less likely to report food insecurity if they were wealthier or had higher household income. Discussion After taking other characteristics into consideration, households in urban areas were at higher risk for food insecurity. These findings point to the need for expanding food assistance programs to more urban areas to help mitigate the impact of lockdowns on more vulnerable households.

  🖺 Full Text HTML: Food Insecurity amid COVID-19 Lockdowns: Assessing Sociodemographic Indicators of Vulnerability in Harar and Kersa, Ethiopia
• What can New Zealand bats tell us about Coronaviruses? -
  The current Covid-19 pandemic emphasizes the dramatic consequences of emerging zoonotic pathogens and stimulates the need for an assessment of the evolution and natural cycle of such microbes in a One Health framework. A number of recent studies have revealed an astonishing diversity of bat-borne Coronaviruses, including in insular environments, which can be considered as simplified biological systems suited for the exploration of the transmission cycles of these viruses in nature. In this work, we present two new lineages of alpha Coronaviruses detected by screening the only two extant New Zealand bat species: the lesser short-tailed bat (Mystacina tuberculata) and the long-tailed bat (Chalinolobus tuberculatus). Infection prevalence reaching 60% in long-tailed bats makes this host-pathogen model relevant for the investigation of maintenance mechanisms in a bat reservoir with peculiar physiological adaptations to temperate climates. A phylogenetic analysis shows that these viral lineages do cluster with Coronaviruses hosted by bat sister species from Australia, supporting co-diversification processes and confirming that the evolution of these viruses is tightly linked to that of their hosts. These patterns provide an interesting framework for further research aiming at elucidating the natural history and biological cycles of these economically-devastating zoonotic viruses.
  🖺 Full Text HTML: What can New Zealand bats tell us about Coronaviruses?
• Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors -
  The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a rapid response by the scientific community to further understand and combat its associated pathologic etiology. A focal point has been on the immune responses mounted during the acute and post-acute phases of infection, but the immediate post-diagnosis phase remains relatively understudied. We sought to better understand the immediate post-diagnosis phase by collecting blood from study participants soon after a positive test and identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14-CD16+ and intermediate CD14+CD16+ monocytes. Additionally, in the lymphocyte compartment, CD8+ T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. Importantly, the identification of these cellular and molecular immune changes occurred at the early stages of COVID-19 disease. These observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19.
  🖺 Full Text HTML: Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors
• Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes -
  RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and optimize their replication and spread in human cells. In IAV, adaptation occurs in all viral proteins, including the viral ribonucleoprotein (RNP) complex. RNPs consists of a copy of the viral RNA polymerase, a double-helical coil of nucleoprotein, and one of the eight segments of the IAV RNA genome. The RNA segments and their transcripts are partially structured to coordinate the packaging of the viral genome and modulate viral mRNA translation. In addition, RNA structures can affect the efficiency of viral RNA synthesis and the activation of host innate immune response. Here, we investigated if RNA structures that modulate IAV replication processivity, so called template loops (t-loops), vary during the adaptation of pandemic and emerging IAV to humans. Using cell culture-based replication assays and in silico sequence analyses, we find that the sensitivity of the IAV H3N2 RNA polymerase to t-loops increased between isolates from 1968 and 2017, whereas the total free energy of t-loops in the IAV H3N2 genome was reduced. This reduction is particularly prominent in the PB1 gene. In H1N1 IAV, we find two separate reductions in t-loop free energy, one following the 1918 pandemic and one following the 2009 pandemic. No destabilization of t-loops is observed in the IBV genome, whereas analysis of SARS-CoV-2 isolates reveals destabilization of viral RNA structures. Overall, we propose that a loss of free energy in the RNA genome of emerging respiratory RNA viruses may contribute to the adaption of these viruses to the human population.
  🖺 Full Text HTML: Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes
• The lasting effects of the pandemic: A time series analysis of first-time speech delays in kids under 5 years of age -

  Given the profound effects of the COVID-19 pandemic on the way individuals interact, we sought to understand if there was an increase in pediatric first-time speech and language delay diagnoses in. We identified children under five years of age with a first-time speech delay diagnosis between January 1, 2018 and February 28, 2023, in Truveta Data. We calculated the monthly rate of first-time speech delay diagnoses per children with an encounter within the last year and no previous speech delay diagnosis. The Seasonal-Trend decomposition using LOESS (STL) method was used to adjust for seasonality. We also compared the difference in means between the 2018/2019 and 2021/2022 time periods. Significant increases in the mean of rates between 2018/2019 and 2021/2022 exist for the overall population and each age strata (p<0.001). Likely the causes of these trends are multifaceted and future research is needed to understand the specific drivers at play.

  🖺 Full Text HTML: The lasting effects of the pandemic: A time series analysis of first-time speech delays in kids under 5 years of age
• The secretory IgA (sIgA) response in human milk against the SARS-CoV-2 Spike is highly durable and neutralizing for at least 1 year of lactation post-infection -

  Although in the early pandemic period, COVID-19 pathology among young children and infants was typically less severe compared to that observed among adults, this has not remained entirely consistent as SARS-CoV-2 variants have emerged. There is an enormous body of evidence demonstrating the benefits of human milk antibodies (Abs) in protecting infants against a wide range of enteric and respiratory infections. It is highly plausible that the same holds true for protection against SARS-CoV-2, as this virus infects cells of the gastrointestinal and respiratory mucosae. Understanding the durability of a human milk Ab response over time after infection is critical. Previously, we examined the Abs present in milk of those recently infected with SARS-CoV-2, and concluded that the response was secretory IgA (sIgA)-dominant and that these titers were highly correlated with neutralization potency. The present study aimed to monitor the durability of the SARS-CoV-2 IgA and secretory Ab (sAb) response in milk from COVID-19-recovered lactating individuals over 12 months, in the absence of vaccination or re-infection. This analysis revealed a robust and durable Spike-specific milk sIgA response, that at 9-12 months after infection, 88% of the samples exhibited titers above the positive cutoff for IgA and 94% were above cutoff for sAb. Fifty percent of participants exhibited less than a 2-fold reduction of Spike-specific IgA through 12 months. A strong significant positive correlation between IgA and sAb against Spike persisted throughout the study period. Nucleocapsid-specific Abs were also assessed, which revealed significant background or cross reactivity of milk IgA against this immunogen, as well as limited/inconsistent durability compared to Spike titers. These data suggests that lactating individuals are likely to continue producing Spike-specific Abs in their milk for 1 year or more, which may provide critical passive immunity to infants against SARS-CoV-2 throughout the lactation period.

  🖺 Full Text HTML: The secretory IgA (sIgA) response in human milk against the SARS-CoV-2 Spike is highly durable and neutralizing for at least 1 year of lactation post-infection
• Evaluation of the implementation and effects of management through care and services pathways: A protocol study -

  Background: In 2015, the Government of Quebec undertook a vast reorganization of its health and social services network. This reform mainly aimed to promote and simplify access to services for the population, contributing to the improvement of the quality and safety of care, and increasing the efficiency and effectiveness of the network. Since 2016, several health care organizations (HCOs) have pushed reform even further by developing management through care and service pathways (MCSP). This study aims to identify, in a processual manner, the different factors involved in implementing MCSP in different HCOs, in the turbulent context of the COVID-19 pandemic. Method: The methodology of this research project is based on developmental evaluation. The objective of developmental evaluation is to guide organizations and actors in the adaptation and development of innovations in complex and turbulent environments. Data will be collected over a three-year period using five strategies: i) organizational questionnaires; ii) analysis of clinical-administrative databases; iii) documentary analysis (grey and scientific literatures); iv) participant observations and v) semi-structured interviews with key actors involved in the implementation of MCSP. Discussion: In addition to the operationalization of pathways, the implementation of MCSP i) involves transforming the governance of the health care organization both at the strategic and operational levels and ii) is a demanding process that requires changes in practices, modifications in the allocation and configuration of resources and the development of new collaborations between the different actors in the organization, the partners and the users involved in this transformation. Several studies claim that governance innovations can create conditions that are favourable to the emergence of innovations in terms of available services and responding to the needs of populations. This research will develop knowledge of the factors involved in implementing MCSP in complex and turbulent contexts and propose scale-up across the province.

  🖺 Full Text HTML: Evaluation of the implementation and effects of management through care and services pathways: A protocol study
• An Open One-Step RT-qPCR for SARS-CoV-2 detection -

  The COVID-19 pandemic has resulted in millions of deaths globally, and while several diagnostic systems were proposed, real-time reverse transcription polymerase chain reaction (RT-PCR) remains the gold standard. However, diagnostic reagents, including enzymes used in RT-PCR, are subject to centralized production models and intellectual property restrictions, which present a challenge for less developed countries. With the aim of generating a standardized One-Step open RT-qPCR protocol to detect SARS-CoV-2 RNA in clinical samples, we purified and tested recombinant enzymes and a non-proprietary buffer. The protocol utilized M-MLV RT and Taq DNA pol enzymes to perform a Taqman probe-based assay. Synthetic RNA samples were used to validate the One-Step RT-qPCR components, and the kit showed comparable sensitivity to approved commercial kits. The One-Step RT-qPCR was then tested on clinical samples and demonstrated similar performance to commercial kits in terms of positive and negative calls. This study represents a proof of concept for an open approach to developing diagnostic kits for viral infections and diseases, which could provide a cost-effective and accessible solution for less developed countries.

  🖺 Full Text HTML: An Open One-Step RT-qPCR for SARS-CoV-2 detection
• The German Job Search Panel 2.0: The Pandemic Cohort -
  The German Job Search Panel (GJSP) comprises survey data from workers who registered as jobseekers expecting the termination of their jobs. The data include an exceptionally broad range of measures of health and well-being, among other information. A first cohort was invited to participate between November 2017 and May 2019 (Hetschko et al., 2022). In 2020, the outbreak of the Covid-19 pandemic drastically changed the macroeconomic environment of the German labor market and, in the process, the challenges associated with job search. We therefore decided to sample a second cohort of initially employed jobseekers from July 2020 to February 2021 (GJSP 2.0). Combining the two GJSP cohorts allows researchers to examine if and how the pandemic altered the experience of job search. This data report describes the pandemic cohort of the GJSP, changes to sampling, recruitment and questionnaires compared to the first cohort and documents determinants of participation and panel attrition.
  🖺 Full Text HTML: The German Job Search Panel 2.0: The Pandemic Cohort
• A Multi-Epitope/CXCL11 Prime/Pull Coronavirus Mucosal Vaccine Boosts the Frequency and the Function of Lung-Resident CD4+ and CD8+ Memory T Cells and Protects Against COVID-19-like Symptoms and Death Caused by SARS-CoV-2 infection -
  The pandemic of the coronavirus disease 2019 (COVID-19) has created the largest global health crisis in almost a century. Following exposure to SARS-CoV-2, the virus particles replicate in the lungs, induce a cytokine storm and potentially cause life-threatening inflammatory disease. Low frequencies of function SARS-CoV-2-specific CD4+ and CD8+ T cells in the lungs of COVID-19 patients were associated with severe cases of COVID-19. The apparent low level of T cell-attracting CXCL9, CXCL10, and CXCL11 chemokines in infected lungs may not be sufficient enough to assure the sequestration and/or homing of CD4+ and CD8+ T cells from the circulation into infected lungs. We hypothesize that a Coronavirus vaccine strategy that boosts the frequencies of functional SARS-CoV-2-specific CD4+ and CD8+ T cells in the lungs would lead to better protection against SARS-CoV-2 infection, COVID19-like symptoms, and death. In the present study, we designed and pre-clinically tested the safety, immunogenicity, and protective efficacy of a novel multi-epitope//CXCL11 prime/pull mucosal Coronavirus vaccine. This prime/pull vaccine strategy consists of intranasal delivery of a lung-tropic adeno-associated virus type 9 (AAV-9) vector that incorporates highly conserved human B, CD4+ CD8+ cell epitopes of SARS-CoV-2 (prime) and pulling the primed B and T cells into the lungs using the T cell attracting chemokine, CXCL-11 (pull). We demonstrated that immunization of HLA-DR0101/HLA-A0201/hACE2 triple transgenic mice with this multi-epitope//CXCL11 prime/pull Coronavirus mucosal vaccine: (i) Increased the frequencies of CD4+ and CD8+ TEM, TCM, and TRM cells in the lungs; and (ii) reduced COVID19-like symptoms, lowered virus replication, and prevented deaths following challenge with SARS-CoV-2. These findings discuss the importance of bolstering the number and function of lung-resident memory CD4+ and CD8+ T cells for better protection against SARS-CoV-2 infection, COVID-19-like symptoms, and death.
  🖺 Full Text HTML: A Multi-Epitope/CXCL11 Prime/Pull Coronavirus Mucosal Vaccine Boosts the Frequency and the Function of Lung-Resident CD4+ and CD8+ Memory T Cells and Protects Against COVID-19-like Symptoms and Death Caused by SARS-CoV-2 infection
• Modifications to the SR-Rich Region of the SARS-CoV-2 Nucleocapsid Regulate Self-Association and Attenuate RNA Interactions -
  The nucleocapsid protein (N) of SARS-CoV-2 is essential for virus replication, genome packaging, and maturation. N is comprised of two folded domains that are separated by a highly conserved, disordered, Ser/Arg-rich linker, and flanked by disordered tails. Using NMR spectroscopy and analytical ultracentrifugation we identify an alpha-helical region in the linker that undergoes concentration dependent self-association. NMR and gel shift assays show that the linker binds viral RNA but this binding is dampened by both phosphorylation and a naturally occurring mutation, whereas in contrast, RNA binding to the full-length protein is not affected. Interestingly, phase separation with RNA is significantly reduced upon phosphorylation but enhanced with the mutation. We attribute these differences to changes in the linker helix self-association which dissociates upon phosphorylation but forms more stable higher order oligomers in the variant. These data provide a structural mechanism for how the linker region contributes to protein-protein interactions, RNA-protein interactions, liquid-liquid phase separation and N protein regulation.
  🖺 Full Text HTML: Modifications to the SR-Rich Region of the SARS-CoV-2 Nucleocapsid Regulate Self-Association and Attenuate RNA Interactions

From Clinical Trials

From PubMed

• Utilization of Marine Seaweeds as a Promising Defense Against COVID-19: a Mini-review - COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which mainly affects the respiratory system. It has been declared as a “pandemic” in March 2020 by the World Health Organization due to the high spreading rate. SARS-CoV-2 binds with the angiotensin-converting enzyme 2 (ACE2) receptors on the cell surface which leads to the downregulation of ACE2 and upregulation of angiotensin-converting enzyme (ACE) receptors. The elevated level of…

• Identification of Host Proteins Interacting with IBV S1 Based on Tracheal Organ Culture - Infectious bronchitis virus (IBV) belongs to the gamma-coronavirus genus of Coronaviridae and causes serious infectious diseases in the poultry industry. However, only a few IBV strains can infect avian passage cell lines, seriously hindering the progress of basic research on IBV pathogenesis. Whereas IBV field strains can replicate in tracheal ring organ culture (TOC) without any previous adaptation in chicken embryos or primary cells. In this study, to investigate the potential use of TOC as…

• Transcription Factor Driven Gene Regulation in COVID-19 Patients - SARS-CoV-2 and its many variants have caused a worldwide emergency. Host cells colonised by SARS-CoV-2 present a significantly different gene expression landscape. As expected, this is particularly true for genes that directly interact with virus proteins. Thus, understanding the role that transcription factors can play in driving differential regulation in patients affected by COVID-19 is a focal point to unveil virus infection. In this regard, we have identified 19 transcription factors which…

• Genes Involved in miRNA Biogenesis Are Not Downregulated in SARS-CoV-2 Infection - miRNAs, small non-coding RNAs that regulate gene expression, are involved in various pathological processes, including viral infections. Virus infections may interfere with the miRNA pathway through the inhibition of genes involved in miRNA biogenesis. A reduction in the number and the levels of miRNAs expressed in nasopharyngeal swabs of patients with severe COVID-19 was lately observed by us, pointing towards the potential of miRNAs as possible diagnostic or prognostic biomarkers for…

• In Silico and In Vitro Evaluation of Some Amidine Derivatives as Hit Compounds towards Development of Inhibitors against Coronavirus Diseases - Coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and influenza A virus, require the host proteases to mediate viral entry into cells. Rather than targeting the continuously mutating viral proteins, targeting the conserved host-based entry mechanism could offer advantages. Nafamostat and camostat were discovered as covalent inhibitors of TMPRSS2 protease involved in viral entry. To circumvent their limitations, a reversible inhibitor might be required. Considering nafamostat structure and…

• The Dimeric Peptide (KKYRYHLKPF)₂K Shows Broad-Spectrum Antiviral Activity by Inhibiting Different Steps of Chikungunya and Zika Virus Infection - Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I)(2)K [(KKYRYHLKPF)(2)K], a peptide derived from the Bothropstoxin-I toxin in the venom of the Bothrops jararacussu snake, showed antiviral activity against SARS-CoV-2. In this study, we assessed the activity of…

• GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, has given rise to many new variants with increased transmissibility and the ability to evade vaccine protection. The 78-kDa glucose-regulated protein (GRP78) is a major endoplasmic reticulum (ER) chaperone that has been recently implicated as an essential host factor for SARS-CoV-2 entry and infection. In this study, we investigated the efficacy of YUM70, a small molecule inhibitor of…

• IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein - Less than a year after the global emergence of the coronavirus SARS-CoV-2, a novel vaccine platform based on mRNA technology was introduced to the market. Globally, around 13.38 billion COVID-19 vaccine doses of diverse platforms have been administered. To date, 72.3% of the total population has been injected at least once with a COVID-19 vaccine. As the immunity provided by these vaccines rapidly wanes, their ability to prevent hospitalization and severe disease in individuals with…

• Long COVID and Hybrid Immunity among Children and Adolescents Post-Delta Variant Infection in Thailand - This study aimed to assess long COVID, and describe immunogenicity against Omicron variants following BNT162b2 vaccination. A prospective cohort study was conducted among children (aged 5-11) and adolescents (aged 12-17) who had SARS-CoV-2 infection from July to December 2021 (Delta predominant period). Long COVID symptoms were assessed by questionnaires at 3 months after infection. Immunogenicity was evaluated by using a surrogate virus-neutralizing antibody test (sVNT) against the Omicron…

• Natural Product-Based Screening for Lead Compounds Targeting SARS CoV-2 M^pro - Drugs that cure COVID-19 have been marketed; however, this disease continues to ravage the world without becoming extinct, and thus, drug discoveries are still relevant. Since M^(pro) has known advantages as a drug target, such as the conserved nature of the active site and the absence of homologous proteins in the body, it receives the attention of many researchers. Meanwhile, the role of traditional Chinese medicine (TCM) in the control of epidemics in China has also led to a focus on natural…

• Hydroxypropyl-β-Cyclodextrin Depletes Membrane Cholesterol and Inhibits SARS-CoV-2 Entry into HEK293T-ACE^hi Cells - Vaccination has drastically decreased mortality due to coronavirus disease 19 (COVID-19), but not the rate of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alternative strategies such as inhibition of virus entry by interference with angiotensin-I-converting enzyme 2 (ACE2) receptors could be warranted. Cyclodextrins (CDs) are cyclic oligosaccharides that are able to deplete cholesterol from membrane lipid rafts, causing ACE2 receptors to relocate to areas devoid of lipid…

• Discovery of Chalcone-Based Hybrid Structures as High Affinity and Site-Specific Inhibitors against SARS-CoV-2: A Comprehensive Structural Analysis Based on Various Host-Based and Viral Targets - Previous studies indicated that natural-based chalcones have significant inhibitory effects on the coronavirus enzymes 3CLpro and PLpro as well as modulation of some host-based antiviral targets (HBATs). In this study, a comprehensive computational and structural study was performed to investigate the affinity of our compound library consisting of 757 chalcone-based structures (CHA-1 to CHA-757) for inhibiting the 3CLpro and PLpro enzymes and against twelve selected host-based targets. Our…

• Drug Potency Prediction of SARS-CoV-2 Main Protease Inhibitors Based on a Graph Generative Model - The prediction of a ligand potency to inhibit SARS-CoV-2 main protease (M-pro) would be a highly helpful addition to a virtual screening process. The most potent compounds might then be the focus of further efforts to experimentally validate their potency and improve them. A computational method to predict drug potency, which is based on three main steps, is defined: (1) defining the drug and protein in only one 3D structure; (2) applying graph autoencoder techniques with the aim of generating a…

• Novel Polymyxin-Inspired Peptidomimetics Targeting the SARS-CoV-2 Spike:hACE2 Interface - Though the bulk of the COVID-19 pandemic is behind, the search for effective and safe anti-SARS-CoV-2 drugs continues to be relevant. A highly pursued approach for antiviral drug development involves targeting the viral spike (S) protein of SARS-CoV-2 to prevent its attachment to the cellular receptor ACE2. Here, we exploited the core structure of polymyxin B, a naturally occurring antibiotic, to design and synthesize unprecedented peptidomimetics (PMs), intended to target contemporarily two…

• Structure-Based Design of Potent Peptidomimetic Inhibitors Covalently Targeting SARS-CoV-2 Papain-like Protease - The papain-like protease (PL^(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a critical role in the proteolytic processing of viral polyproteins and the dysregulation of the host immune response, providing a promising therapeutic target. Here, we report the structure-guide design of novel peptidomimetic inhibitors covalently targeting SARS-CoV-2 PL^(pro). The resulting inhibitors demonstrate submicromolar potency in the enzymatic assay (IC(50) = 0.23 μM) and…

From Patent Search