Targeting Lipid Kinases Offers New Hope Against Emerging Viruses

A new collaborative study highlights the potential of dual targeting lipid kinases as a strategy against emerging viruses. Researchers from institutions including the University of Eastern Finland, Stanford University, and the US Army Medical Research Institute of Infectious Diseases have discovered a chemical probe that selectively inhibits two critical lipid kinases: PIKfyve and PIP4K2C. This approach could provide a higher barrier to resistance compared to traditional antiviral therapies, particularly in treating newly emerging viral infections.

The study, published in Nature Communications, details how inhibiting these enzymes, which are essential for cell signaling and membrane trafficking, could improve the effectiveness of antiviral strategies. The findings suggest that the small molecule inhibitor RMC-113 significantly suppresses the replication of several RNA viruses, including SARS-CoV-2, in laboratory settings.

Significance of Dual Inhibition

Lipid kinases, such as PIKfyve and PIP4K2C, are pivotal in the life cycle of viruses. By targeting these enzymes, researchers aim to disrupt various pathways that viruses exploit for replication. According to Christopher Asquith, Senior Researcher at the University of Eastern Finland, this dual inhibition represents a promising therapeutic intervention that can overcome the limitations of direct-acting antivirals.

Asquith noted the collaboration among multiple institutions has enabled researchers to address complex questions that would be challenging to tackle independently. The study demonstrates that RMC-113 engages specifically with both lipid kinases, showcasing its potential as a broad-spectrum antiviral treatment.

Advanced lipidomics revealed that RMC-113 alters the phosphoinositide signature induced by SARS-CoV-2, linking its antiviral effects to the inhibition of PIP4K2C and PIKfyve. The research also uncovered PIP4K2C’s crucial roles in the virus’s entry, RNA replication, and assembly, identifying it as a viable target for antiviral drugs.

Broader Implications for Virus Treatment

The findings suggest that targeting host-directed pathways, particularly those involving lipid kinases, could provide a broader range of action against multiple viruses. This is significant as many viruses utilize similar host pathways for replication. The study emphasizes the need for innovative approaches to antiviral drug development, especially in light of the ongoing challenges posed by emerging viral threats.

The research team integrated proteomics, single-cell transcriptomics, and functional assays to reveal how PIP4K2C interacts with the non-structural protein 6 of SARS-CoV-2, affecting autophagic flux—an essential process for cellular function. RMC-113’s ability to reverse the impairment of autophagic flux caused by the virus highlights a novel mechanism of antiviral action.

As the global scientific community faces the ongoing threat of emerging viruses, the discovery of RMC-113 and its dual inhibition strategy marks a significant advancement in the pursuit of effective antiviral therapies. The collaborative effort underscores the importance of interdisciplinary research in addressing pressing health challenges.

For further details, the full study can be accessed at Nature Communications, with the reference: Karim, M., et al. (2025). PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2. doi.org/10.1038/s41467-025-61759-1.