The structural flexibility of RNA underlies fundamental biological processes, but there are no methods for exploring the multiple conformations adopted by RNAs in vivo. We developed cross-linking of matched RNAs and deep sequencing (COMRADES) for in-depth RNA conformation capture, and a pipeline for the retrieval of RNA structural ensembles. Using COMRADES, we determined the architecture of the Zika virus RNA genome inside cells, and identified multiple site-specific interactions with human noncoding RNAs.

Highlights d Comprehensive RNA-RNA networks of the SARS-CoV-2 genome and subgenomes inside cells d Long-range structures spanning thousands of bases resulting in dynamic topologies d Multiple site-specific interactions between host and virus RNAs d An arch around the ribosomal frameshifting element is under purifying selection