Effect of long-term care and pandemic wave on relative risk of COVID-19-related infection, hospitalization and mortality in people living with dementia: A population-based cohort study.

BackgroundPeople living with dementia (PLWD) are vulnerable to serious COVID-19 illness and death but the contribution of various factors including long-term care (LTC), pandemic wave, hospitalization, comorbidities, and underlying neurological health remains unclear.ObjectiveTo investigate the relative risk of SARS-CoV-2 infection, hospitalization, and mortality (COVID-19 and non-COVID-19) in PLWD compared to those without dementia, by living circumstance and pandemic wave, while controlling for additional risk factors.MethodsA cohort of people 65 and up with dementia, including Alzheimer's disease, was propensity score matched to a control cohort using linked population-level health records.

A novel class of broad-spectrum active-site-directed 3C-like protease inhibitors with nanomolar antiviral activity against highly immune-evasive SARS-CoV-2 Omicron subvariants.

Antivirals with broad coronavirus activity are important for treating high-risk individuals exposed to the constantly evolving SARS-CoV-2 variants of concern (VOCs) as well as emerging drug-resistant variants. We developed and characterized a novel class of active-site-directed 3-chymotrypsin-like protease (3CLpro) inhibitors (). Our lead direct-acting antiviral (DAA), , is a non-covalent, non-peptide with a dissociation constant of 170 nM against recombinant SARS-CoV-2 3CLpro.

Discovery of lead natural products for developing pan-SARS-CoV-2 therapeutics.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health crisis. The reduced efficacy of therapeutic monoclonal antibodies against emerging SARS-CoV-2 variants of concern (VOCs), such as omicron BA.5 subvariants, has underlined the need to explore a novel spectrum of antivirals that are effective against existing and evolving SARS-CoV-2 VOCs.

Characterizing Longitudinal Antibody Responses in Recovered Individuals Following COVID-19 Infection and Single-Dose Vaccination: A Prospective Cohort Study.

Background: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time.

Methods: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov.

DEEMD: Drug Efficacy Estimation Against SARS-CoV-2 Based on Cell Morphology With Deep Multiple Instance Learning.

Drug repurposing can accelerate the identification of effective compounds for clinical use against SARS-CoV-2, with the advantage of pre-existing clinical safety data and an established supply chain. RNA viruses such as SARS-CoV-2 manipulate cellular pathways and induce reorganization of subcellular structures to support their life cycle. These morphological changes can be quantified using bioimaging techniques.

A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic.

The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced owing to emerging variants of concern. Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against variants of concern.

Photodynamic and Contact Killing Polymeric Fabric Coating for Bacteria and SARS-CoV-2.

The development of low-cost, non-toxic, scalable antimicrobial textiles is needed to address the spread of deadly pathogens. Here, we report a polysiloxane textile coating that possesses two modes of antimicrobial inactivation, passive contact inactivation through amine/imine functionalities and active photodynamic inactivation through the generation of reactive oxygen species (ROS). This material can be coated and cross-linked onto natural and synthetic textiles through a simple soak procedure, followed by UV cure to afford materials exhibiting no aqueous leaching and only minimal leaching in organic solvents.

Intra-host evolutionary dynamics of the hepatitis C virus among people who inject drugs.

Most individuals chronically infected with hepatitis C virus (HCV) are asymptomatic during the initial stages of infection and therefore the precise timing of infection is often unknown. Retrospective estimation of infection duration would improve existing surveillance data and help guide treatment. While intra-host viral diversity quantifications such as Shannon entropy have previously been utilized for estimating duration of infection, these studies characterize the viral population from only a relatively short segment of the HCV genome.

A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice.

The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced against emerging variants of concern (VOCs) . Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs .

Hijacking of Lipid Droplets by Hepatitis C, Dengue and Zika Viruses-From Viral Protein Moonlighting to Extracellular Release.

Hijacking and manipulation of host cell biosynthetic pathways by human enveloped viruses are essential for the viral lifecycle. members, including hepatitis C, dengue and Zika viruses, extensively manipulate host lipid metabolism, underlining the importance of lipid droplets (LDs) in viral infection. LDs are dynamic cytoplasmic organelles that can act as sequestration platforms for a unique subset of host and viral proteins.

Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9.

In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n=72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9.

Development and validation of a real-time, reverse transcription PCR assay for rapid and low-cost genotyping of hepatitis C virus genotypes 1a, 1b, 2, and 3a.

Hepatitis C virus (HCV) infection affects millions of people and leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Treatment regimen selection requires HCV genotype (Gt) and Gt 1 subtype determination. Use of a laboratory developed, reverse transcription (RT)-PCR assay was explored as a low-cost, high-throughput screening approach for the major HCV genotypes and subtypes in North America.

Methamphetamine injecting is associated with phylogenetic clustering of hepatitis C virus infection among street-involved youth in Vancouver, Canada.

Background: Among prospective cohorts of people who inject drugs (PWID), phylogenetic clustering of HCV infection has been observed. However, the majority of studies have included older PWID, representing distant transmission events. The aim of this study was to investigate phylogenetic clustering of HCV infection among a cohort of street-involved youth.

A molecular phylogenetics-based approach for identifying recent hepatitis C virus transmission events.

Unlabelled: Improved surveillance methods are needed to better understand the current hepatitis C virus (HCV) disease burden and to monitor the impact of prevention and treatment interventions on HCV transmission dynamics. Sanger sequencing (HCV NS5B, HVR1 and Core-E1-HVR1) and phylogenetics were applied to samples from individuals diagnosed with HCV in British Columbia, Canada in 2011. This included individuals with two or three sequential samples collected <1 year apart.

Differentiation of acute from chronic hepatitis C virus infection by nonstructural 5B deep sequencing: a population-level tool for incidence estimation.

Unlabelled: The ability to classify acute versus chronic hepatitis C virus (HCV) infections at the time of diagnosis is desirable to improve the quality of surveillance information. The aim of this study was to differentiate acute from chronic HCV infections utilizing deep sequencing. HCV nonstructural 5B (NS5B) amplicons (n = 94) were generated from 77 individuals (13 acute and 64 chronic HCV infections) in British Columbia, Canada, with documented seroconversion time frames.

Human subtilase SKI-1/S1P is a master regulator of the HCV Lifecycle and a potential host cell target for developing indirect-acting antiviral agents.

HCV infection is a major risk factor for liver cancer and liver transplantation worldwide. Overstimulation of host lipid metabolism in the liver by HCV-encoded proteins during viral infection creates a favorable environment for virus propagation and pathogenesis. In this study, we hypothesize that targeting cellular enzymes acting as master regulators of lipid homeostasis could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with human Flaviviridae viruses such as hepatitis C virus (HCV), whose assembly and pathogenesis depend on interaction with lipid droplets (LDs).

In-cell selectivity profiling of membrane-anchored and replicase-associated hepatitis C virus NS3-4A protease reveals a common, stringent substrate recognition profile.

The need to identify anti-Flaviviridae agents has resulted in intensive biochemical study of recombinant nonstructural (NS) viral proteases; however, experimentation on viral protease-associated replication complexes in host cells is extremely challenging and therefore limited. It remains to be determined if membrane anchoring and/or association to replicase-membrane complexes of proteases, such as hepatitis C virus (HCV) NS3-4A, plays a regulatory role in the substrate selectivity of the protease. In this study, we examined trans-endoproteolytic cleavage activities of membrane-anchored and replicase-associated NS3-4A using an internally consistent set of membrane-anchored protein substrates mimicking all known HCV NS3-4A polyprotein cleavage sequences.