Author: Szemiel, Agnieszka M.; Merits, Andres; Orton, Richard J.; MacLean, Oscar; Pinto, Rute Maria; Wickenhagen, Arthur; Lieber, Gauthier; Turnbull, Matthew L.; Wang, Sainan; Mair, Daniel; da Silva Filipe, Ana; Willett, Brian J.; Wilson, Sam J.; Patel, Arvind H.; Thomson, Emma C.; Palmarini, Massimo; Kohl, Alain; Stewart, Meredith E.
Title: In vitro evolution of Remdesivir resistance reveals genome plasticity of SARS-CoV-2 Cord-id: 7eivapcw Document date: 2021_2_10
ID: 7eivapcw
Snippet: Remdesivir (RDV) is used widely for COVID-19 patients despite varying results in recent clinical trials. Here, we show how serially passaging SARS-CoV-2 in vitro in the presence of RDV selected for drug-resistant viral populations. We determined that the E802D mutation in the RNA-dependent RNA polymerase was sufficient to confer decreased RDV sensitivity without affecting viral fitness. Analysis of more than 200,000 sequences of globally circulating SARS-CoV-2 variants show no evidence of widesp
Document: Remdesivir (RDV) is used widely for COVID-19 patients despite varying results in recent clinical trials. Here, we show how serially passaging SARS-CoV-2 in vitro in the presence of RDV selected for drug-resistant viral populations. We determined that the E802D mutation in the RNA-dependent RNA polymerase was sufficient to confer decreased RDV sensitivity without affecting viral fitness. Analysis of more than 200,000 sequences of globally circulating SARS-CoV-2 variants show no evidence of widespread transmission of RDV-resistant mutants. Surprisingly, we also observed changes in the Spike (i.e., H69 E484, N501, H655) corresponding to mutations identified in emerging SARS-CoV-2 variants indicating that they can arise in vitro in the absence of immune selection. This study illustrates SARS-CoV-2 genome plasticity and offers new perspectives on surveillance of viral variants. One Sentence Summary SARS-CoV-2 drug resistance & genome plasticity
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