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1.
Health Promot Chronic Dis Prev Can ; 43(5): 260-266, 2023 May.
Article in English, French | MEDLINE | ID: covidwho-2324518

ABSTRACT

Using data from the 2020 and 2021 cycles of the Survey on COVID-19 and Mental Health,we examined suicidal ideation among adults in Canada aged 18 to 34 years. The prevalence of suicidal ideation among adults aged 18 to 34 years was 4.2% in fall 2020 and 8.0% in spring 2021. The subgroup of adults aged 18 to 24 years had the highest prevalence of suicidal ideation, 10.7%, in spring 2021. Prevalence varied by sociodemographic characteristics and tended to be higher among people living in materially deprived areas. Suicidal ideation was strongly associated with pandemic-related stressors respondents experienced.


In spring 2021, the prevalence of suicidal ideation among young adults aged 18 to 34 years was 8.0%. At 10.7%, the prevalence of suicidal ideation was highest in the subgroup of young adults aged 18 to 24 years, in spring 2021. The odds of suicidal ideation were higher among young adults who were White versus racialized, born in Canada versus immigrated to Canada, living with low or middle income, with high school education or less, or living in a materially deprived area. Pandemic-related experiences, stressful events and mental illness were strongly associated with suicidal ideation.


La prévalence des idées suicidaires chez les jeunes adultes de 18 à 34 ans était de 8,0 % au printemps 2021. La prévalence la plus élevée d'idées suicidaires, soit 10,7 %, correspond au sous-groupe des jeunes adultes de 18 à 24 ans au printemps 2021. Les probabilités d'idées suicidaires étaient plus élevées chez les jeunes adultes qui étaient d'origine blanche (par opposition aux membres d'un groupe « racisé ¼), ceux nés au Canada (par opposition à ceux ayant immigré au Canada), ceux vivant avec un revenu faible ou moyen, ceux ayant fait des études de niveau secondaire ou moins et ceux vivant dans un milieu défavorisé sur le plan matériel. Les expériences liées à la pandémie, les événements stressants et la maladie mentale étaient fortement associés aux idées suicidaires.


Subject(s)
COVID-19 , Suicidal Ideation , Humans , Young Adult , Cross-Sectional Studies , Pandemics , Risk Factors , COVID-19/epidemiology , Canada/epidemiology
2.
iScience ; 26(6): 106780, 2023 Jun 16.
Article in English | MEDLINE | ID: covidwho-2308509

ABSTRACT

Among all RNA viruses, coronavirus RNA transcription is the most complex and involves a process termed "discontinuous transcription" that results in the production of a set of 3'-nested, co-terminal genomic and subgenomic RNAs during infection. While the expression of the classic canonical set of subgenomic RNAs depends on the recognition of a 6- to 7-nt transcription regulatory core sequence (TRS), here, we use deep sequence and metagenomics analysis strategies and show that the coronavirus transcriptome is even more vast and more complex than previously appreciated and involves the production of leader-containing transcripts that have canonical and noncanonical leader-body junctions. Moreover, by ribosome protection and proteomics analyses, we show that both positive- and negative-sense transcripts are translationally active. The data support the hypothesis that the coronavirus proteome is much vaster than previously noted in the literature.

3.
Chembiochem ; 24(11): e202300116, 2023 06 01.
Article in English | MEDLINE | ID: covidwho-2300345

ABSTRACT

While vaccines and antivirals are now being deployed for the current SARS-CoV-2 pandemic, we require additional antiviral therapeutics to not only effectively combat SARS-CoV-2 and its variants, but also future coronaviruses. All coronaviruses have relatively similar genomes that provide a potential exploitable opening to develop antiviral therapies that will be effective against all coronaviruses. Among the various genes and proteins encoded by all coronaviruses, one particularly "druggable" or relatively easy-to-drug target is the coronavirus Main Protease (3CLpro or Mpro), an enzyme that is involved in cleaving a long peptide translated by the viral genome into its individual protein components that are then assembled into the virus to enable viral replication in the cell. Inhibiting Mpro with a small-molecule antiviral would effectively stop the ability of the virus to replicate, providing therapeutic benefit. In this study, we have utilized activity-based protein profiling (ABPP)-based chemoproteomic approaches to discover and further optimize cysteine-reactive pyrazoline-based covalent inhibitors for the SARS-CoV-2 Mpro. Structure-guided medicinal chemistry and modular synthesis of di- and tri-substituted pyrazolines bearing either chloroacetamide or vinyl sulfonamide cysteine-reactive warheads enabled the expedient exploration of structure-activity relationships (SAR), yielding nanomolar potency inhibitors against Mpro from not only SARS-CoV-2, but across many other coronaviruses. Our studies highlight promising chemical scaffolds that may contribute to future pan-coronavirus inhibitors.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Cysteine , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Protease Inhibitors/pharmacology , Protease Inhibitors/chemistry , Molecular Docking Simulation
4.
Health Promot Chronic Dis Prev Can ; 43(3): 105-118, 2023 03 15.
Article in English, French | MEDLINE | ID: covidwho-2269327

ABSTRACT

INTRODUCTION: Recent evidence has suggested an increase in suicidal ideation during the COVID-19 pandemic. Our objectives were to estimate the likelihood of suicidal ideation among adults in Canada who experienced pandemic-related impacts and to determine if this likelihood changed during the pandemic. METHODS: We analyzed pooled data for 18 936 adults 18 years or older who responded to two cycles of the Survey on COVID-19 and Mental Health collected from 11 September to 4 December 2020 and from 1 February to 7 May 2021. We estimated the prevalence of suicidal ideation since the pandemic began and conducted logistic regression to evaluate the likelihood of suicidal ideation by adults who experienced pandemic-related impacts, and by factors related to social risk, mental health status, positive mental health indicators and coping strategies. RESULTS: Adults who had adverse pandemic-related experiences were significantly more likely to experience suicidal ideation; a dose-response relationship was evident. People who increased their alcohol or cannabis use, expressed concerns about violence in their home or who had moderate to severe symptoms of depression, anxiety or posttraumatic stress disorder also had significantly higher risk of suicidal ideation. The risk was significantly lower among people who reported high self-rated mental health, community belonging or life satisfaction, who exercised for their mental and/or physical health or who pursued hobbies. CONCLUSION: The COVID-19 pandemic has influenced suicidal ideation in Canada. Our study provides evidence for targeted public health interventions related to suicide prevention.


Subject(s)
COVID-19 , Suicidal Ideation , Adult , Humans , Cross-Sectional Studies , Pandemics , Risk Factors , COVID-19/epidemiology , COVID-19/prevention & control , Canada/epidemiology
5.
ACS Omega ; 7(36): 31935-31944, 2022 Sep 13.
Article in English | MEDLINE | ID: covidwho-2185524

ABSTRACT

The portfolio of SARS-CoV-2 small molecule drugs is currently limited to a handful that are either approved (remdesivir), emergency approved (dexamethasone, baricitinib, paxlovid, and molnupiravir), or in advanced clinical trials. Vandetanib is a kinase inhibitor which targets the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), as well as the RET-tyrosine kinase. In the current study, it was tested in different cell lines and showed promising results on inhibition versus the toxic effect on A549-hACE2 cells (IC50 0.79 µM) while also showing a reduction of >3 log TCID50/mL for HCoV-229E. The in vivo efficacy of vandetanib was assessed in a mouse model of SARS-CoV-2 infection and statistically significantly reduced the levels of IL-6, IL-10, and TNF-α and mitigated inflammatory cell infiltrates in the lungs of infected animals but did not reduce viral load. Vandetanib also decreased CCL2, CCL3, and CCL4 compared to the infected animals. Vandetanib additionally rescued the decreased IFN-1ß caused by SARS-CoV-2 infection in mice to levels similar to that in uninfected animals. Our results indicate that the FDA-approved anticancer drug vandetanib is worthy of further assessment as a potential therapeutic candidate to block the COVID-19 cytokine storm.

6.
ACS Chem Biol ; 17(7): 1937-1950, 2022 07 15.
Article in English | MEDLINE | ID: covidwho-2106315

ABSTRACT

Inhibition of the protein kinase CSNK2 with any of 30 specific and selective inhibitors representing different chemotypes, blocked replication of pathogenic human, bat, and murine ß-coronaviruses. The potency of in-cell CSNK2A target engagement across the set of inhibitors correlated with antiviral activity and genetic knockdown confirmed the essential role of the CSNK2 holoenzyme in ß-coronavirus replication. Spike protein endocytosis was blocked by CSNK2A inhibition, indicating that antiviral activity was due in part to a suppression of viral entry. CSNK2A inhibition may be a viable target for the development of anti-SARS-like ß-coronavirus drugs.


Subject(s)
Coronavirus Infections , Coronavirus , Animals , Antiviral Agents/pharmacology , Coronavirus/genetics , Humans , Mice , Virus Internalization
7.
J Med Chem ; 65(19): 12860-12882, 2022 10 13.
Article in English | MEDLINE | ID: covidwho-2087118

ABSTRACT

From a designed library of indolyl pyrimidinamines, we identified a highly potent and cell-active chemical probe (17) that inhibits phosphatidylinositol-3-phosphate 5-kinase (PIKfyve). Comprehensive evaluation of inhibitor selectivity confirmed that this PIKfyve probe demonstrates excellent kinome-wide selectivity. A structurally related indolyl pyrimidinamine (30) was characterized as a negative control that lacks PIKfyve inhibitory activity and exhibits exquisite selectivity when profiled broadly. Chemical probe 17 disrupts multiple phases of the lifecycle of ß-coronaviruses: viral replication and viral entry. The diverse antiviral roles of PIKfyve have not been previously probed comprehensively in a single study or using the same compound set. Our scaffold is a distinct chemotype that lacks the canonical morpholine hinge-binder of classical lipid kinase inhibitors and has a non-overlapping kinase off-target profile with known PIKfyve inhibitors. Our chemical probe set can be used by the community to further characterize the role of PIKfyve in virology.


Subject(s)
Coronavirus , Phosphatidylinositol 3-Kinases , Antiviral Agents/pharmacology , Morpholines , Phosphates , Phosphatidylinositols , Phosphoinositide-3 Kinase Inhibitors
8.
Obesity ; 28(10):1802-1805, 2020.
Article in English | ProQuest Central | ID: covidwho-2057529

ABSTRACT

Objective: This study aimed to examine the impact of the coronavirus disease (COVID-19) pandemic on patronage to unhealthy eating establishments in populations with obesity. Methods: Anonymized movement data accounting for roughly 10% of devices in the United States at 138,989 unhealthy eating locations from December 1,2019, through April 2020 and the percentage of adults with obesity, the poverty rate, and the food environment index in 65% of United States counties were collected and merged. A cluster corrected Poisson spline regression was performed predicting patronage by day, the percentage of adults with obesity in the establishment's county, the county's poverty rate, and its food environment index, as well as their interactions. Results: Patronage to unhealthy eating establishments was higher where there was a higher percentage of the adult population with obesity. A similar pattern was observed for counties with a lower food environment index. These disparities appear to have increased as the COVID-19 pandemic spread. Conclusions: These results suggest unhealthy eating patterns during the COVID-19 pandemic are higher in already at-risk populations. Policy makers can use these findings to motivate interventions and programs aimed at increasing healthy food intake in at-risk communities during crises.

9.
Nat Rev Drug Discov ; 21(12): 881-898, 2022 12.
Article in English | MEDLINE | ID: covidwho-2008295

ABSTRACT

Covalent drugs have been used to treat diseases for more than a century, but tools that facilitate the rational design of covalent drugs have emerged more recently. The purposeful addition of reactive functional groups to existing ligands can enable potent and selective inhibition of target proteins, as demonstrated by the covalent epidermal growth factor receptor (EGFR) and Bruton's tyrosine kinase (BTK) inhibitors used to treat various cancers. Moreover, the identification of covalent ligands through 'electrophile-first' approaches has also led to the discovery of covalent drugs, such as covalent inhibitors for KRAS(G12C) and SARS-CoV-2 main protease. In particular, the discovery of KRAS(G12C) inhibitors validates the use of covalent screening technologies, which have become more powerful and widespread over the past decade. Chemoproteomics platforms have emerged to complement covalent ligand screening and assist in ligand discovery, selectivity profiling and target identification. This Review showcases covalent drug discovery milestones with emphasis on the lessons learned from these programmes and how an evolving toolbox of covalent drug discovery techniques facilitates success in this field.


Subject(s)
COVID-19 Drug Treatment , Protein Kinase Inhibitors , Humans , Drug Discovery/methods , Ligands , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins p21(ras)/metabolism , SARS-CoV-2 , Structure-Activity Relationship
10.
Medicine (Baltimore) ; 101(30): e29786, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967939

ABSTRACT

BACKGROUND: Individuals on immunosuppressive therapies experience greater morbidity and mortality due to vaccine-preventable illnesses, but there are low rates of adherence to immunization guidelines within this population. OBJECTIVE: To determine the effectiveness of clinician-led education, patient-centered dialogue, and immediately available immunization on influenza vaccination uptake in patients taking immunosuppressive therapies. METHOD: We used a controlled before-and-after quasi-experimental design to evaluate our quality improvement intervention occurring from September 2019 to March 2020, with follow-up through July 2020. The study included 2 dermatology practices wherein nursing staff offered influenza vaccination during patient rooming (standard care). Within each practice, clinicians either implemented the intervention or provided only standard care. Patients received the intervention or standard care depending on the clinician they visited. Patients seen at the 2 clinics during the intervention period were included in analyses if they were taking or newly prescribed immunosuppressant medication at the time of their visit. We examined influenza immunization status for 3 flu seasons: 2017-2018 (preintervention), 2018-2019 (preintervention), and 2019-2020 (intervention). INTERVENTION: Immunosuppressed patients initially declining an influenza vaccine were provided dermatologist-led education on the benefits of immunization. Dermatologists explored and addressed individual patients' immunization concerns. Influenza vaccination was then offered immediately postdialogue. RESULTS: Analyses included 201 dermatology patients who were prescribed or currently taking immunosuppressive medication (intervention group [72.6%], comparison group [27.4%]). During the intervention period, 91.1% of the intervention group received influenza vaccination compared to 56.4% of the comparison group. Vaccination trends from 2018-2019 (preintervention) to 2019-2020 (intervention) differed significantly between groups (χ2 = 22.92, P < .001), with greater improvement in the intervention group. In 2019-2020, influenza vaccination was more likely in the intervention group relative to the comparison group (odds ratio: 16.22, 95% confidence interval: 5.55-47.38). In the subset of patients that had never received an influenza vaccine, influenza immunization in 2019-2020 was more common in the intervention group (75.8%, 25/33) relative to the comparison group (13.3%, 2/15, P < .001). CONCLUSION: The intervention successfully addressed vaccine hesitancy and improved influenza immunization rates in an immunosuppressed population receiving care from a specialty clinic. Implementing a similar model across specialty clinics may improve vaccination rates for influenza, coronavirus disease 2019, and other vaccine-preventable illnesses in other populations.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Humans , Influenza Vaccines/therapeutic use , Influenza, Human/drug therapy , Influenza, Human/prevention & control , Vaccination , Vaccination Hesitancy
11.
Syst Rev ; 11(1): 146, 2022 07 20.
Article in English | MEDLINE | ID: covidwho-1951340

ABSTRACT

BACKGROUND: Indigenous Peoples are impacted by industrial resource development that takes place on, or near, their communities. Existing literature on impacts of industrial resource development on Indigenous Peoples primarily focus on physical health outcomes and rarely focus on the mental health impacts. To understand the full range of long-term and anticipated health impacts of industrial resource development on Indigenous communities, mental health impacts must be examined. It is well-established that there is a connection between the environment and Indigenous wellbeing, across interrelated dimensions of mental, physical, emotional, and spiritual health. METHODS: This paper identifies how the Community Advisory Team and a team of Indigenous and settler scholars will conduct the review. The literature search will use the OVID interface to search Medline, Embase, PsycINFO, and Global Health databases. Non-indexed peer-reviewed journals related to Indigenous health or research will be scanned. Books and book chapters will be identified in the Scopus and PsycINFO databases. The grey literature search will also include Google and be limited to reports published by government, academic, and non-profit organizations. Reference lists of key publications will be checked for additional relevant publications, including theses, dissertations, reports, and other articles not retrieved in the online searches. Additional sources may be recommended by team members. Included documents will focus on Indigenous Peoples in North America, South America, Australia, Aotearoa New Zealand, and Circumpolar regions, research that reports on mental health, and research that is based on land loss connected to dams, mines, agriculture, or petroleum development. Literature that meets the inclusion criteria will be screened at the title/abstract and full-text stages by two team members in Covidence. The included literature will be rated with a quality appraisal tool and information will be extracted by two team members; a consensus of information will be reached and be submitted for analysis. DISCUSSION: The synthesized evidence from this review is relevant for land use policy, health impact assessments, economic development, mental health service planning, and communities engaging in development projects. SYSTEMATIC REVIEW REGISTRATION: Registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration number CRD42021253720 ).


Subject(s)
Delivery of Health Care , Mental Health , Humans , Indigenous Peoples , Population Groups , Systematic Reviews as Topic
12.
Sci Rep ; 12(1): 9622, 2022 06 10.
Article in English | MEDLINE | ID: covidwho-1947488

ABSTRACT

This network meta-analysis (NMA) assessed the efficacy of remdesivir in hospitalized patients with COVID-19 requiring supplemental oxygen. Randomized controlled trials of hospitalized patients with COVID-19, where patients were receiving supplemental oxygen at baseline and at least one arm received treatment with remdesivir, were identified. Outcomes included mortality, recovery, and no longer requiring supplemental oxygen. NMAs were performed for low-flow oxygen (LFO2); high-flow oxygen (HFO2), including NIV (non-invasive ventilation); or oxygen at any flow (AnyO2) at early (day 14/15) and late (day 28/29) time points. Six studies were included (N = 5245 patients) in the NMA. Remdesivir lowered early and late mortality among AnyO2 patients (risk ratio (RR) 0.52, 95% credible interval (CrI) 0.34-0.79; RR 0.81, 95%CrI 0.69-0.95) and LFO2 patients (RR 0.21, 95%CrI 0.09-0.46; RR 0.24, 95%CrI 0.11-0.48); no improvement was observed among HFO2 patients. Improved early and late recovery was observed among LFO2 patients (RR 1.22, 95%CrI 1.09-1.38; RR 1.17, 95%CrI 1.09-1.28). Remdesivir also lowered the requirement for oxygen support among all patient subgroups. Among hospitalized patients with COVID-19 requiring supplemental oxygen at baseline, use of remdesivir compared to best supportive care is likely to improve the risk of mortality, recovery and need for oxygen support in AnyO2 and LFO2 patients.


Subject(s)
COVID-19 Drug Treatment , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Humans , Oxygen/therapeutic use , Randomized Controlled Trials as Topic , Treatment Outcome
13.
Antiviral Res ; 204: 105360, 2022 08.
Article in English | MEDLINE | ID: covidwho-1881679

ABSTRACT

Coronaviruses are a class of single-stranded, positive-sense RNA viruses that have caused three major outbreaks over the past two decades: Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All outbreaks have been associated with significant morbidity and mortality. In this study, we have identified and explored conserved binding sites in the key coronavirus proteins for the development of broad-spectrum direct acting anti-coronaviral compounds and validated the significance of this conservation for drug discovery with existing experimental data. We have identified four coronaviral proteins with highly conserved binding site sequence and 3D structure similarity: PLpro, Mpro, nsp10-nsp16 complex(methyltransferase), and nsp15 endoribonuclease. We have compiled all available experimental data for known antiviral medications inhibiting these targets and identified compounds active against multiple coronaviruses. The identified compounds representing potential broad-spectrum antivirals include: GC376, which is active against six viral Mpro (out of six tested, as described in research literature); mycophenolic acid, which is active against four viral PLpro (out of four); and emetine, which is active against four viral RdRp (out of four). The approach described in this study for coronaviruses, which combines the assessment of sequence and structure conservation across a viral family with the analysis of accessible chemical structure - antiviral activity data, can be explored for the development of broad-spectrum drugs for multiple viral families.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Antiviral Agents/pharmacology , Drug Discovery , Humans , SARS-CoV-2
14.
Health Rep ; 33(5): 13-21, 2022 05 18.
Article in English | MEDLINE | ID: covidwho-1856607

ABSTRACT

Introduction: Data from the first round of the nationally representative Survey on COVID-19 and Mental Health (SCMH) revealed that the prevalence of recent suicidal ideation in the fall of 2020 in Canada did not differ significantly from that in the pre-pandemic period in 2019. The objective of the present study was to reassess the prevalence of recent suicidal ideation in the spring of 2021. Methods: The prevalence of suicidal ideation among adults in Canada was examined using the 2021 SCMH (conducted between February 1 and May 7, 2021), and it was compared with the prevalence in the 2019 Canadian Community Health Survey. Unadjusted logistic regression analysis was used to assess the differential likelihood of reporting suicidal ideation in population subgroups. Results: Among adults in Canada, the prevalence of suicidal ideation since the pandemic began was 4.2%, which was significantly higher than the pre-pandemic prevalence of 2.7% in 2019. A statistically significant increase in prevalence was observed among females and males, age groups younger than 65, and several other sociodemographic groups, as well as in British Columbia, the Prairie provinces and Ontario. People who were younger than 65 years, were born in Canada, had lower educational attainment, or were never married were significantly more likely to report suicidal ideation than others during the pandemic. Conclusion: As the second year of the pandemic began, the prevalence of recent suicidal ideation in Canada was higher than it had been before the pandemic in 2019. Continuous monitoring of suicide-related outcomes and risks is necessary so that population-level changes can be detected and inform public health action.


Subject(s)
COVID-19 , Adult , British Columbia , Canada/epidemiology , Female , Humans , Male , Mental Health , Prevalence , Risk Factors , Suicidal Ideation
15.
J Med Educ Curric Dev ; 9: 23821205221096370, 2022.
Article in English | MEDLINE | ID: covidwho-1833254

ABSTRACT

Universities and medical schools often work towards operationalizing their shared mission of facilitating community-engaged work independently. Based on their experience teaching the COVID-19 Elective course at Stanford University School of Medicine, the authors proposed a novel solution for universities and medical schools to achieve an interdisciplinary collaboration within a diverse student population by creating targeted, project-based, and community-engaged courses for addressing emergent health needs. In this article, the authors discuss their curriculum, which was created using Kern's six-step approach for curriculum development, to address emergent health needs related to the novel coronavirus pandemic. The curriculum provides an opportunity for universities and medical schools to advance community health, educate students across the medical and non-medical education continuum, and foster interdisciplinary cooperation.

17.
18.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.03.05.483025

ABSTRACT

While vaccines and antivirals are now being deployed for the current SARS-CoV-2 pandemic, we require additional antiviral therapeutics to not only effectively combat SARS-CoV-2 and its variants, but also future coronaviruses. All coronaviruses have relatively similar genomes that provide a potential exploitable opening to develop antiviral therapies that will be effective against all coronaviruses. Among the various genes and proteins encoded by all coronaviruses, one particularly druggable or relatively easy-to-drug target is the coronavirus Main Protease (3CLpro or Mpro), an enzyme that is involved in cleaving a long peptide translated by the viral genome into its individual protein components that are then assembled into the virus to enable viral replication in the cell. Inhibiting Mpro with a small-molecule antiviral would effectively stop the ability of the virus to replicate, providing therapeutic benefit. In this study, we have utilized activity-based protein profiling (ABPP)-based chemoproteomic approaches to discover and further optimize cysteine-reactive pyrazoline-based covalent inhibitors for the SARS-CoV-2 Mpro. Structure-guided medicinal chemistry and modular synthesis of di- and tri-substituted pyrazolines bearing either chloroacetamide or vinyl sulfonamide cysteine-reactive warheads enabled the expedient exploration of structure-activity relationships (SAR), yielding nanomolar potency inhibitors against Mpro from not only SARS-CoV-2, but across many other coronaviruses. Our studies highlight promising chemical scaffolds that may contribute to future pan-coronavirus inhibitors.

19.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.03.04.22271706

ABSTRACT

This network meta-analysis (NMA) assessed the efficacy of remdesivir in hospitalized patients with COVID-19 requiring supplemental oxygen. Randomized controlled trials of hospitalized patients with COVID-19, where patients were receiving supplemental oxygen at baseline and at least one arm received treatment with remdesivir, were identified. Outcomes included mortality, recovery, and no longer requiring supplemental oxygen. NMAs were performed for low-flow oxygen (LFO2); high-flow oxygen (HFO2), including NIV; or oxygen at any flow (AnyO2) at early (day 14/15) and late (day 28/29) time points. Six studies were included (N=5,245 patients) in the NMA. Remdesivir lowered early and late mortality among AnyO2 patients (risk ratio (RR) 0.52, 95% credible interval (CrI) 0.34-0.79; RR 0.81, 95%CrI 0.69-0.95) and LFO2 patients (RR 0.21, 95%CI 0.09-0.46; RR 0.24, 95%CI 0.11-0.48); no improvement was observed among HFO2 patients. Improved early and late recovery was observed among LFO2 patients (RR 1.22, 95%CrI 1.09-1.38; RR 1.17, 95%CrI 1.09-1.28). Remdesivir also lowered the requirement for oxygen support among all patient subgroups. Among hospitalized patients with COVID-19 requiring supplemental oxygen at baseline, use of remdesivir compared to best supportive care is likely to improve the risk of mortality, recovery and need for oxygen support in AnyO2 and LFO2 patients.


Subject(s)
COVID-19
20.
2021 ASEE Virtual Annual Conference, ASEE 2021 ; 2021.
Article in English | Scopus | ID: covidwho-1696356

ABSTRACT

The first Architectural Engineering (AE) class at the University of Waterloo (UW) began in fall of 2018. The compulsory co-op work experience, architectural studio component each semester, and collaboration with the UW School of Architecture are features of the program that make it unique in North America, just to name a few. In order to provide an introduction at the beginning of the school year that would adequately capture the essence of the program, a tried-and-true hands-on engineering project model at UW called 'Design Days' was adapted for the AE program. In 2018, the inaugural two-day design-build project called 'AE Design Days' was held wherein first-year students worked in groups to design a piece, or set, of furniture that enhanced an assigned site in a UW Engineering building. The objectives of the project were to provide an 'ice-breaking' opportunity between students, as well as with the faculty;introduce the students to the AE program content, especially as it relates to the design process;provide opportunities for the students to work with their hands building models;and, to allow for the course instructors to gauge the skillset and prior knowledge of the incoming students [1]. Following the success of the first AE Design Days event, the same project model was implemented in 2019, with minor modifications to improve the event logistics and student experience. This paper discusses the planning and implementation of the most recent edition of the event held in 2020 and the dramatic overhaul required as a result of the COVID-19 pandemic and the transition to online/remote learning. With new constraints and potential opportunities associated with the online learning platform, the event saw its overall intent and structure shift to prime the students for working online in an AE context, and to provide a vessel to introduce students to the program and build new relationships, since these efforts are crucial at the start of the program, and do not come as naturally when online. The event drew a large crowd, with nearly 100% of the 124 students participating and dozens of volunteers coming from various groups (students, faculty, and industry), and was shown to be well-received by the results of surveys. The paper concludes with a reflection of the perceived successes and challenges of the event. Also, recommendations are discussed in the context of the virtual event platform, which can be extended to general AE online learning. © American Society for Engineering Education, 2021

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