Mpox: Scientists offer better understanding of tecovirimat resistance
February 12, 2025
Scientists at the Institut Pasteur have made a breakthrough in understanding resistance to tecovirimat, the primary antiviral used to treat mpox. Their study, published in Nature Microbiology, reveals how the drug interacts with the F13 enzyme, which some viral strains mutate to develop resistance. This research is crucial as mpox cases surge in the Democratic Republic of Congo and beyond, with WHO declaring another global public health emergency in August 2024. By uncovering tecovirimat’s mechanism of action, researchers are paving the way for the development of new, more effective antiviral treatments that can combat resistant mpox strains worldwide.
As global mpox cases continue to rise, scientists at the Institut Pasteur have made a critical discovery regarding resistance to tecovirimat, the primary antiviral used to treat the disease. Their study, published in Nature Microbiology, sheds light on how certain mpox strains evade treatment by mutating the F13 enzyme, a key component in viral particle formation.
Tecovirimat, while generally well-tolerated, has shown limitations against resistant strains. The Institut Pasteur team used biochemical and computational methods to analyze how tecovirimat binds to the F13 enzyme, effectively blocking viral spread. However, when F13 mutates, this mechanism fails, leading to drug resistance. Their findings suggest that tecovirimat acts as molecular “glue” that binds F13 phospholipases together, preventing their role in viral replication.
This research comes at a crucial time. With the Democratic Republic of Congo and neighboring countries experiencing a surge in mpox cases, WHO declared a renewed public health emergency in August 2024. France has updated vaccination strategies, and Santé publique France has reported 215 cases in 2024 and 10 so far in 2025.
Understanding tecovirimat’s limitations underscores the need for new antiviral therapies. Institut Pasteur researchers have already begun developing alternative treatments targeting mpox variants, ensuring that future outbreaks can be managed more effectively. As resistance continues to emerge, this study is a vital step toward safeguarding global health.