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Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1

by Dimitrios G. Anastasakis, Daniel Benhalevy, Nicolas Çuburu, Nihal Altan-Bonnet, Markus Hafner

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elusive. By integrating RNA-seq, ribosome footprinting, and ChIP-seq in A549 cells we found that NSP1 predominantly represses transcription of immune-related genes by favoring Histone 3 Lysine 9 dimethylation (H3K9me2). G9a/GLP H3K9 methyltransferase inhibitor UNC0638 restored expression of antiviral genes and restricted SARS-CoV-2 replication. Our multi-omics study unravels an epigenetic mechanism underlying host immune evasion by SARS-CoV-2 NSP1. Elucidating the factors involved in this phenomenon, may have implications for understanding and treating viral infections and other immunomodulatory diseases.

Impact of deintensifying hypoglycaemic drugs in older adults with type 2 diabetes: protocol for an emulation of a target trial

Por: Christiaens · A. · Simon-Tillaux · N. · Thompson · W. · Sinclair · A. J. · Henrard · S. · Boland · B. B. · Slaouti-Jegou · Y. · Lekens · B. · Bonnet-Zamponi · D. · Tubach · F. · Zerah · L.
Introduction

In older adults with type 2 diabetes (T2D), overtreatment with hypoglycaemic drugs (HDs: sulfonylureas, glinides and/or insulins) is frequent and associated with increased 1-year mortality. Deintensification of HD is thus a key issue, for which evidence is though limited. The primary objective of this study will be to estimate the effect of deintensifying HD on clinical outcomes (hospital admission or death) within 3 months in older adults (≥75 years) with T2D.

Methods

We will emulate with real-world data a target trial, within The Health Improvement Network cohort, a large-scale database of data collected from electronic medical records of 2000 general practitioners in France. From 1 January 2010 to 28 February 2019, we will include eligible patients ≥75 years who will have T2D, a stable dose of HDs, glycated haemoglobin A1c (HbA1c) value 75 mmol/mol within 1 year. Participants will be followed from baseline to 12 months after randomisation, administrative censoring, or death, whichever occurs first. A pooled logistic regression will be used to estimate the treatment effect on the incidence of the outcomes.

Dissemination and ethics

No ethical approval is needed for using retrospectively this fully anonymised database. The results will be disseminated during conferences and through publications in scientific journals.

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