Guanylate binding proteins (GBPs) as novel therapeutic targets against single-stranded RNA viruses

Guanylate-binding proteins (GBPs) are interferon-inducible proteins that demonstrate a wide spectrum of antimicrobial activity. The capacity of GBPs to undergo nucleotide-dependent oligomerization and to exhibit GTPase activity, together with their membrane-anchoring properties, constitutes a compelling research domain within mechanistic biology. However, the current knowledge regarding GBPs is fragmentary, warranting a comprehensive review to elucidate their significance and to delineate their multifaceted roles in human health and disease. In this review, we provide a detailed overview of the transcriptional regulation of GBPs by examining their role in infectious and autoimmune diseases, and highlight their potential as novel therapeutic targets, particularly in the context of managing emerging and re-emerging RNA viral infections, which are a major global health threat. Additionally, this review emphasizes the significance of GBPs as a prognostic biomarker for understanding the outcome of viral diseases characterized by endothelial dysfunction, especially in the context of flaviviruses, such as dengue virus, serving as a model system. GBP1's antiviral role and its importance in vascular dysfunction, and GBP2/5's broad antiviral effect of furin-mediated inhibition have shown therapeutic promise. Further research is warranted on other GBP targets, mechanistic variations affecting GBP activity, and their potential as biomarkers. Moreover, there is a need to explore GBPs, and their combined effects on viruses, their link to vascular health and ferroptosis, and strategies for maintaining GBP levels during infection.