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Deep sequencing analysis of the mutant spectrum of SARS-CoV-2 replicating in the absence or presence of ribavirin

ABSTRACT: Atypical mutational spectrum of SARS-CoV-2 replicating in the presence of ribavirin

PROVIDER: PRJEB56440 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR10359645_1.fastq.gz	Fastqsanger.gz
	ERR10359645_2.fastq.gz	Fastqsanger.gz
	ERR10359646_1.fastq.gz	Fastqsanger.gz
	ERR10359646_2.fastq.gz	Fastqsanger.gz
	ERR10359648_1.fastq.gz	Fastqsanger.gz

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Expression data of genome-length HCV RNA-replicating OL8(3.5Y) cells and OL8(3.5Y)-derived ribavirin-resistant cells

Project description:Ribavirin (RBV) is a potential partner of interferon-based therapy and recently approved therapy using direct acting antivirals for patients with chronic hepatitis C, However, the precise mechanisms undelying RBV action against hepatitis C virus (HCV) replication are not yet understood. To clarify this point, we established RBV-resistant cell lines from RBV-sensitive HCV RNA-replicating cell line, OL8(3.5Y), and characterized their features. We used microarrays to compare the gene expression pattern between OL8(3.5Y) cells and three RBV-resistant cells and identified genes commonly altered by more than four-fold among RBV-resistant cells compared with the OL8(3.5Y) cells.

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Atypical Mutational Spectrum of SARS-CoV-2 Replicating in the Presence of Ribavirin.

Project description:We report that ribavirin exerts an inhibitory and mutagenic activity on SARS-CoV-2-infecting Vero cells, with a therapeutic index higher than 10. Deep sequencing analysis of the mutant spectrum of SARS-CoV-2 replicating in the absence or presence of ribavirin indicated an increase in the number of mutations, but not in deletions, and modification of diversity indices, expected from a mutagenic activity. Notably, the major mutation types enhanced by replication in the presence of ribavirin were A→G and U→C transitions, a pattern which is opposite to the dominance of G→A and C→U transitions previously described for most RNA viruses. Implications of the inhibitory activity of ribavirin, and the atypical mutational bias produced on SARS-CoV-2, for the search for synergistic anti-COVID-19 lethal mutagen combinations are discussed.

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Expression data of genome-length HCV RNA-replicating OL8(3.5Y) cells and OL8(3.5Y)-derived ribavirin-resistant cells

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