Search

The oral protease inhibitor nirmatrelvir is of key importance for prevention of severe coronavirus disease 2019 (COVID-19). To facilitate resistance monitoring, we studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape from nirmatrelvir in cell culture. Resistant variants harbored combinations of substitutions in the SARS-CoV-2 main protease (Mpro). Reverse genetics revealed that E166V and L50F + E166V conferred high resistance in infectious culture, replicon, and Mpro systems. While L50F, E166V, and L50F + E166V decreased replication and Mpro activity, L50F and L50F + E166V variants had high fitness in the infectious system. Naturally occurring L50F compensated for fitness cost of E166V and promoted viral escape. Molecular dynamics simulations revealed that E166V and L50F + E166V weakened nirmatrelvir-Mpro binding. Polymerase inhibitor remdesivir and monoclonal antibody bebtelovimab retained activity against nirmatrelvir-resistant variants, and combination with nirmatrelvir enhanced treatment efficacy compared to individual compounds. These findings have implications for monitoring and ensuring treatments with efficacy against SARS-CoV-2 and emerging sarbecoviruses.

M��ltider er dagligt tilbagevendende begivenheder, som kr��ver kendskab til, viden om og refleksioner over m��ltidets kompleksitet. Artiklens empiriske grundlag viser, at m��ltidet ofte ikke har formulerede p��dagogiske m��l, men er pr��get af tilf��ldigheder og den enkelte medarbejders v��rdier. Ny forskning viser, at m��ltidet ikke prioriteres som en v��sentlig p��dagogisk aktivitet. Form��let med artiklen er at synligg��re de dilemmaer og den kompleksitet, der er forbundet med m��ltidet, samt belyse, p�� hvilken m��de et neurop��dagogisk perspektiv kan kvalificere det specialp��dagogiske arbejde. Empirien i artiklen er en case baseret p�� fire eksamensopgaver, som analyseres ud fra neurop��dagogikkens genstandsfelt. Artiklens resultat viser, hvordan den neurop��dagogiske tilgang kan udvikle nye synteser og give nye foruds��tninger for refleksioner. I artiklen konkluderes det, at kompleksiteten i m��ltidet best��r af indre, ydre og relationelle processer, og at observation, refleksion og analyse af borgerens tegn kan give st��rre forst��else for borgerens adf��rd i et hjerne-, krop- og omverdenperspektiv., UCN Perspektiv, Nr. 10 (2021): Neurop��dagogik ��� perspektiver p�� l��rings- og forandringsprocesser

Usages of the Past in Roman Historiography contains 11 articles on how the Ancient Roman historians used, and manipulated, the past. What did they seek to accomplish by participating in its re-creation, what tools did they have at their disposal to do so, and which underlying conceptualisations of history can we glimpse behind their efforts? Key themes include the impact of the transformation from Republic to Empire on the production of history, the nature of intertextuality in historical writing, and the frontiers between history and other literary genres. The volume, edited by Aske Damtoft Poulsen and Arne Jönsson, encompasses diverse approaches to the study of Roman history and historiography, with contributors from the UK, US, Sweden, Germany, Denmark, and Italy.