Replication and single-cycle delivery of SARS-CoV-2 replicons.

Ricardo-Lax, Inna; Luna, Joseph M; Thao, Tran Thi Nhu; Le Pen, Jérémie; Yu, Yingpu; Hoffmann, H-Heinrich; Schneider, William M; Razooky, Brandon S et al. · Science · 2021

basic_science · Level V

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Abstract

Molecular virology tools are critical for basic studies of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. Experimental systems that do not rely on viruses capable of spread are needed for potential use in lower-containment settings. In this work, we use a yeast-based reverse genetics system to develop spike-deleted SARS-CoV-2 self-replicating RNAs. These noninfectious self-replicating RNAs, or replicons, can be trans-complemented with viral glycoproteins to generate replicon delivery particles for single-cycle delivery into a range of cell types. This SARS-CoV-2 replicon system represents a convenient and versatile platform for antiviral drug screening, neutralization assays, host factor validation, and viral variant characterization.

Medical subject headings