RIG-I Activators

The class of RIG-I activators encompasses a diverse range of chemicals that directly or indirectly modulate the activation of the retinoic acid-inducible gene I (RIG-I) pathway, a key component of the cellular antiviral response. Poly(I:C), a synthetic analog of double-stranded RNA, stands out as a direct activator, engaging RIG-I in recognizing viral RNA and initiating antiviral signaling. Imiquimod, a Toll-like receptor 7 agonist, indirectly boosts RIG-I activity by enhancing TLR signaling pathways. Furthermore, chemicals like DMXAA, resveratrol, and retinoic acid showcase the interconnectedness of RIG-I activation with other cellular pathways, such as cGAS-STING, sirtuin 1 (SIRT1), and retinoid receptor signaling, respectively.

The indirect modulators include 2-aminopurine and 5-fluorouracil, which influence RIG-I by interfering with RNA recognition and synthesis. Dibutyryl cAMP and PMA, through their impact on the cAMP-PKA axis and protein kinase C (PKC) signaling, respectively, highlight the intricate regulatory networks converging on RIG-I activation. Epigenetic modulators like 5-aza-2'-deoxycytidine and butyrate unveil the importance of DNA methylation and histone acetylation in shaping the RIG-I pathway's responsiveness. Additionally, compounds such as NDGA and butyrate exemplify the indirect regulation of RIG-I through cellular oxidative stress and short-chain fatty acid metabolism. Understanding the nuanced interactions of these chemicals with the RIG-I pathway provides insights into the complex web of cellular defense mechanisms against viral infections. The RIG-I activators offer a platform for dissecting the molecular intricacies of antiviral immunity, showcasing the diverse strategies employed by cells to combat viral threats.