The receptor binding domain (RBD) of the spike glycoprotein of the coronavirus SARS-CoV-2 (CoV2-S) binds to the human angiotensin-converting enzyme 2 (ACE2) representing the initial contact point for leveraging the infection cascade. We used an automated selection process and identified an aptamer that specifically interacts with CoV2-S. The aptamer does not bind to the RBD of CoV2-S and does not block the interaction of CoV2-S with ACE2. Nevertheless, infection studies revealed potent and specific inhibition of pseudoviral infection by the aptamer. The present study opens up new vistas in developing SARS-CoV2 infection inhibitors, independent of blocking the ACE2 interaction of the virus, and harnesses aptamers as potential drug candidates and tools to disentangle hitherto inaccessible infection modalities, which is of particular interest in light of the increasing number of escape mutants that are currently being reported.
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http://dx.doi.org/10.1002/anie.202100316 | DOI Listing |
Alzheimers Dement
December 2024
Case Western Reserve University, Cleveland, OH, USA.
Background: Traumatic Brain Injury (TBI) is one of the most common nonheritable causes of Alzheimer's disease (AD). However, there is lack of effective treatment for both AD and TBI. We posit that network-based integration of multi-omics and endophenotype disease module coupled with large real-world patient data analysis of electronic health records (EHR) can help identify repurposable drug candidates for the treatment of TBI and AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Imperial College London, London, United Kingdom; UK Dementia Research Institute, Care Research and Technology Centre, London, United Kingdom.
Background: Close to 23% of unplanned hospital admissions for people living with dementia (PLWD) are due to potentially preventable causes such as severe urinary tract infections (UTIs), falls, and respiratory problems. These affect the well-being of PLWD, cause stress to carers and increase pressure on healthcare services.
Method: We use routinely collected in-home sensory data to monitor nocturnal activity and sleep data.
Gamma-secretases play a pivotal role in the generation of Aβ peptides. Mutations in these enzymes that cause early-onset, autosomal dominant AD shift Aβ production towards generation of longer peptides. We have recently shown that the mutation-induced shifts in the ratio of short-to-long Aβ peptides not only inform about mutation pathogenicity but also allow experimental prediction of the age at dementia onset.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Tulane University, New Orleans, LA, USA.
Background: Vascular dementia (VaD), the second most common cause of dementia, is characterized by cognitive decline due to reduced cerebral blood flow and blood-brain barrier disruption. Current evidence demonstrates that not only are VaD patients at higher risk of severe COVID-19 illness and mortality, but also that pre-existing cognitive dysfunction/dementia is associated with increased COVID-19 incidence. Conversely, SARS-CoV-2 infection alone worsens dementia-related mild cognitive impairment (MCI) and increases risk of cognitive decline, supported by similar fMRI findings demonstrating hypoperfusion.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Centre for Healthy Brain Ageing (CHeBA), University of New South Wales, UNSW Sydney, NSW, Australia.
Background: The effects of the COVID-19 pandemic extend beyond the viral impact and include social and psychological effects of the ensuing lockdowns and restrictions. Australia's lengthy lockdowns present an opportunity to study changes in the physical and mental wellbeing of older adults resulting from extended social isolation, a known risk factor for dementia, in the absence of high infection or mortality rates.
Method: Sydney Memory and Ageing Study, Sydney Centenarian Study, and CogSCAN study participants were mailed questionnaires about in-person and remote social contact and access to resources during the 2020 Sydney lockdown.
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