Auranofin and Redox-Sensitive Regulation of Viral Entry and NF-kB Signaling
This article examines how the FDA-approved compound Auranofin modulates host-cell pathways involved in viral entry and inflammatory signaling. Researchers found that Auranofin has a dual effect at the cellular level: it reduces the efficiency of viral entry into cells and suppresses inflammatory signaling pathways. Rather than blocking a single entry route, Auranofin alters host‑cell conditions in ways that make viral entry less favorable.
Specifically, Auranofin was shown to interfere with viral entry mechanisms through redox‑dependent changes in membrane organization and ACE2 receptor dynamics. The ACE2 receptor, which SARS‑CoV‑2 uses to attach to cells, becomes more mobile within the cell membrane under these conditions. Because ACE2 localization and mobility are influenced by the cellular redox environment, changes in intracellular oxidative balance may alter attachment efficiency. In addition, Auranofin suppresses activation of the NF-kB signaling pathway, which plays a central role in cellular inflammatory responses and is often dysregulated during viral infection.
Viral Redox Pathways
If we think of the body as a machine, then Redox helps keep it running smoothly. Redox is the balance of oxidants and antioxidants in the body. It’s important because it supports energy-related cellular processes, helps with cellular growth, supports protection against cellular damage, and plays a role in the body’s response to infection and disease. When the Redox system is functioning as it should, the body is healthy.
Viruses disrupt the Redox environment. Viral infection can increase the production of reactive oxygen species (ROS) in host cells to aid in the virus’s life cycle, which in turn throws off the balance of oxidants and antioxidants in the body. Additionally, viruses weaken antioxidant systems. This infection-induced oxidative stress further offsets the balance.
When cells are facing threats, like that of a virus, ROS act as signaling molecules that influence cellular pathways, including those involving NF‑κB. NF‑κB primarily regulates inflammatory and immune‑related gene expression, which can influence overall cellular responses during infection.
Viruses like SARS-CoV-2 interfere with NF-kB signaling in one of two ways. First, they can activate NF-kB signaling to help with virus production. Second, they can inhibit it to make it easier for the virus to evade detection. Some viruses use both methods by initially stimulating the NF-kB signaling to aid in replication and then suppressing it to allow the virus to spread.
The FDA-approved Auranofin has been shown to modulate NF-κB signaling in cellular models of viral infection, including SARS-CoV-2. Auronofin has been shown to suppress SARS-Cov-2-induced NR-κB activation and reduce the efficiency of viral entry into cells. By altering the cellular redox environment and inflammatory signaling, Auranofin influences conditions that help maintain redox balance between oxidants and antioxidants at the cellular level.
