Comparison of Viral RNA–Host Protein Interactomes Across Pathogenic RNA Viruses Informs Rapid Antiviral Drug Discovery for SARS-CoV-2

This study investigated the interactions between viral RNAs (vRNAs) and host proteins for three RNA virus pathogens: SARS-CoV-2, Zika, and Ebola. Using ChIRP-MS, researchers identified both common and virus-specific host responses and vRNA-associated proteins that influence viral infection. Notably, SARS-CoV-2 was found to exploit the host factor IGF2BP1 to stabilize its vRNA and enhance viral translation. The study's findings led to the identification of several FDA-approved drugs, such as Cepharanthine, as broad-spectrum antivirals effective in cells and hACE2 transgenic mice. A combination of Cepharanthine and Trifluoperazine showed high potency against the SARS-CoV-2 B.1.351 variant. This research demonstrated the value of a comparative vRNA–host protein interactome approach in antiviral drug discovery.