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MeSH Disease

HGNC Genes

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SARS-CoV-2 proteins


SARS-CoV-2 Proteins
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    Consistent and High-Frequency Identification of an Intra-Sample Genetic Variant of SARS-CoV-2 with Elevated Fusogenic Properties

    Authors: Lynda Rocheleau; Geneviève Laroche; Kathy Fu; Marceline Côté; Patrick M Giguère; Marc-André Langlois; Martin Pelchat; Peter Mohr; Remo Gamboni; Thanos D. Halazonetis; Kai-Thomas Schneider; Kristian Daniel Ralph Roth; Philipp Kuhn; Peggy Riese; Dorina Schäckermann; Janin Korn; Allan Koch; Susanne Zock-Emmenthal; Marlies Becker; Margitta Scholz; Gustavo Marçal Schmidt Garcia Moreira; Esther Veronika Wenzel; Giulio Russo; Hendrikus S.P. Garritsen; Sebastian Casu; Andreas Gerstner; Günter Roth; Andreas Hermann; Thomas Schirrmann; Stefan Dübel; André Frenzel; Joop Van den Heuvel; Luka Cicin-Sain; Maren Schubert; Michael Hust

    doi:10.1101/2020.12.03.409714 Date: 2020-12-03 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has a genome comprised of a ~30K nucleotides non-segmented, positive single-stranded RNA. Although its RNA-dependent RNA polymerase PROTEIN exhibits exonuclease proofreading activity, viral sequence diversity can be induced by replication errors and host factors. These variations can be observed in the population of viral sequences isolated from infected host cells and are not necessarily reflected in the genome of transmitted founder viruses. We profiled intra-sample genetic diversity of SARS-CoV-2 variants using 15,289 high-throughput sequencing datasets from infected individuals and infected cell lines. Most of the genetic variations observed, including C->U and G->U, were consistent with errors due to heat-induced DNA damage during sample processing, and/or sequencing protocols. Despite high mutational background, we confidently identified intra-variable positions recurrent in the samples analyzed, including several positions at the end of the gene encoding the viral S protein PROTEIN. Notably, most of the samples possesses a C->A missense mutation resulting in the S protein PROTEIN lacking the last 20 amino acids (S{Delta}20). Here we demonstrate that S{Delta}20 exhibits increased cell-to-cell fusion and syncytia formations MESHD. Our findings are suggestive of the consistent emergence of high-frequency viral quasispecies that are not horizontally transmitted but involved in intra-host infection MESHD and spread. Author summaryThe severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) and its associated disease, COVID-19 MESHD, has caused significant worldwide mortality and unprecedented economic burden. Here we studied the intra-host genetic diversity of SARS-CoV-2 genomes and identified a high-frequency and recurrent non-sense mutation yielding a truncated form of the viral spike protein PROTEIN, in both human COVID-19 MESHD samples and in cell culture experiments. Through the use of a functional assay, we observed that this truncated spike protein PROTEIN displays an elevated fusogenic potential and forms syncytia. Given the high frequency at which this mutation independently arises across various samples, it can be hypothesized that this deletion mutation provides a selective advantage to viral replication and may also have a role in pathogenesis in humans.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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