While the MPOX virus is now circulating in humans, researchers from the Pasteur Institute today explore new treatments to compensate for the growing ineffectiveness of Tecovirimat, the main antiviral used against infection.
- The MPOX virus, formerly located in Africa, extends worldwide and resists the main treatment, tecovirimat. Researchers from the Pasteur Institute have identified that this resistance comes from mutations on the enzyme F13, preventing the action of the drug.
- “We have shown that tecovirimat acts as a kind of glue which assembles two F13 phospholipases between them and which prevents it from fulfilling its role in the dissemination of viral particles,” explains Pablo Guardado-Calvo.
- These discoveries pave the way to new antivirals to better combat MPOX, while the World Health Organization (WHO) declared in August 2024 a new international health emergency. In France, the High Authority for Health (HAS) has updated vaccination recommendations.
The MPOX virus, initially present in animals and formerly confined to endemic areas of Africa, now circulates in humans and on a global scale. The disease begins with a feverish phase (aches, headache, fatigue …) followed by rashes over the whole body. Since 2022, successive epidemics have emerged, including in France, where 215 cases have been reported in 2024 and 10 since January 1, 2025. Faced with this resurgence, scientists from the Institut Pasteur explore new therapeutic options, especially in Reason for the growing resistance of the virus to the main antiviral used: tecovirimat. Their work was published in the journal Microbiology nature.
A resistance of the decrypted virus
If Tecovirimat, well tolerated, blocks the spread of the MPOX virus, some variants, however, have mutations that make it ineffective. In 2022, in the United States, around 1% of patients treated in Tecovirimat developed drug resistance. “The objective was to better understand the reasons for the resistance to the treatment of certain variants of the virus”indicates Pablo Guardado-Calvo, head of the unit of structural biology of infectious diseases at the Pasteur Institute.
Confirming previous studies, researchers first observed that Tecovirimat -resistant MPOX variants all have mutations in the phospholipase F13, a key enzyme in the formation of the external envelope of the viral particle. The hypothesis was therefore that the drug interacts with the enzyme F13 to block the infection, an impossible blocking when this enzyme is mutated.
“We have therefore analyzed the structure of phospholipase F13 which allowed us to specify the interactions between the drug and the enzyme, explains Pablo Guardado- Calvo. We have shown that tecovirimat acts as a kind of glue which assembles two F13 phospholipases between them and which prevents it from fulfilling its role in the dissemination of viral particles. “ Their work has thus made it possible to explain the mode of action of the drug and to understand why the variants bearing these mutations make the antiviral treatment ineffective.
A public health emergency
These discoveries pave the way for new antiviral treatments. “There are still many mysterious points in the action of tecovirimat but our study allows to take a first step, Considers Pablo Guardado-Calvo. This understanding is essential for the development of new therapeutic approaches, effective regardless of MPOX strains. “ Researchers from the Pasteur Institute are continuing their work to develop new molecules capable of bypassing these changes and better fighting MPOX infections.
Due to increased propagation in the Democratic Republic of Congo and in several neighboring countries for several months, the World Health Organization (WHO) said in August 2024 a new public health emergency. In France, the High Authority for Health (HAS) has updated its vaccination recommendations for those most at risk.
