RNA–protein interactomes as invaluable resources to study RNA viruses: Insights from SARS CoV‐2 studies

Understanding the molecular mechanisms of severe respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is essential for the successful development of therapeutic strategies against the COVID‐19 pandemic. Numerous studies have focused on the identification of host factors and cellular pathways involved in the viral replication cycle. The speed and magnitude of hijacking the translation machinery of host mRNA, and shutting down host transcription are still not well understood. Since SARS‐CoV‐2 relies on host RNA‐binding proteins for the infection progression, several efforts have been made to define the SARS‐CoV‐2 RNA‐bound proteomes (RNA–protein interactomes). Methodologies that enable the systemic capture of protein interactors of given RNA in vivo have been adapted for the identification of the SARS‐CoV‐2 RNA interactome. The obtained proteomic data aided by genome‐wide and targeted CRISPR perturbation screens, revealed host factors with either pro‐ or anti‐viral activity and highlighted cellular processes and factors involved in host response. We focus here on the recent studies on SARS‐CoV‐2 RNA–protein interactomes, with regard to both the technological aspects of RNA interactome capture methods and the obtained results. We also summarize several related studies, which were used in the interpretation of the SARS‐CoV‐2 RNA–protein interactomes. These studies provided the selection of host factors that are potentially suitable candidates for antiviral therapy. Finally, we underscore the importance of RNA–protein interactome studies in regard to the effective development of antiviral strategies against current and future threats. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications. RNA in Disease and Development > RNA in Disease. RNA Methods > RNA Analyses in Cells.