ArticleProceedings of the National Academy of Sciences of the United States of America2026
Extra gene coding capacity of SARS-CoV-2 provides a virus engineering platform for in vitro and in vivo applications.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The genomic flexibility of orthocoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is showcased by the presence of accessory genes, which vary in number among virus species and strains. Given this flexibility, the viral coding capacity can be artificially expanded to express a heterologous gene from the viral genome, thereby enabling the development of a viral vector platform. Here, we systematically explored the extra gene coding capacity of SARS-CoV-2 by inserting an extra reporter gene at every intergenic region in its genome. We revealed the entire scheme of its extra gene expression and identified a genomic location that stably expresses reporter genes while maintaining the wild-type viral phenotype. Using this construct, we developed a set of fluorescent and luminescent reporter SARS-CoV-2 viruses available for in vivo flow cytometry and in vitro antiviral screening. Flow cytometric analysis with these reporter viruses revealed cell type-specific dynamics of SARS-CoV-2 infection in the lung tissue of K18-hACE2 mice. Our findings offer a platform for SARS-CoV-2 genome engineering, providing a set of reporter viruses for research applications.
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