Mpox: Improved Insights into Tecovirimat Resistance

Overview of Mpox and Recent Epidemics

Mpox, a virus originally found in animals, has transitioned to human populations and has caused significant outbreaks since 2022, particularly outside its endemic regions in Central and West Africa. As reported by Santé publique France, 215 new cases of mpox were documented in 2024 alone, with 10 additional cases reported in the early part of 2025.

Current State of Mpox Infections

The recent surge in mpox infections has been alarming, especially in the Democratic Republic of Congo and neighboring countries. Concerns grew further with the emergence of a possibly more contagious strain, prompting the World Health Organization (WHO) to declare a public health emergency of international concern in mid-August 2024. As a precautionary measure, France’s National Authority for Health has revised its vaccination guidelines for high-risk individuals.

Mpox typically manifests with less severity than smallpox. Initial symptoms resemble those of a mild viral infection, including fever, muscle aches, headaches, and fatigue, followed by characteristic rashes across the body. Despite the less severe nature of the illness, the growing number of cases necessitates continued vigilance.

Treatment Challenges with Tecovirimat

The primary treatment for mpox is tecovirimat, which is recognized for its favorable tolerance profile among patients. This antiviral medication functions by inhibiting the spread of the virus within the body; however, its precise mode of action remains inadequately understood. Additionally, certain viral strains have developed resistance due to mutations, limiting the drug’s effectiveness. Data from the U.S. indicated that approximately 1% of patients treated with tecovirimat in 2022 exhibited resistance, a trend observed in multiple viral clades.

Research Insights from the Institut Pasteur

Recent research at the Institut Pasteur aimed to elucidate the mechanisms behind tecovirimat’s action and the emergence of resistance. The Structural Biology of Infectious Diseases Unit employed biochemical and computational techniques to investigate how tecovirimat prevents poxviruses, including mpox, from exiting infected cells. Pablo Guardado-Calvo, the head of the research team, explained that the objective was to understand why some viral variants resist treatment.

Previously, it was noted that treatment-resistant variants of the mpox virus often harbor mutations in phospholipase F13, a critical enzyme involved in creating the viral envelope. The prevailing hypothesis suggested that tecovirimat interacts with this F13 enzyme to halt viral replication, an effect that becomes nullified when the enzyme undergoes mutation.

Findings on Phospholipase F13

Through their analysis, the researchers successfully characterized the structural attributes of phospholipase F13, pinpointing the interactions between tecovirimat and the enzyme. Their results indicated that tecovirimat acts like an adhesive, binding two F13 enzymes together, thereby preventing the enzyme from performing its essential function in viral particle dissemination.

This foundational study has clarified the mechanism of tecovirimat and highlighted why specific variants with mutations render the antiviral treatment ineffective. Despite the remaining complexities surrounding tecovirimat’s full action, Guardado-Calvo emphasized that understanding these interactions is vital for developing new therapies effective against all strains of the mpox virus.

Future Directions for Antiviral Development

With the insights gained from this research, the team at the Institut Pasteur has initiated the development of new antiviral agents targeting mpox. These efforts are crucial to enhance treatment options for patients and address the ongoing public health challenges posed by mpox and its evolving variants. Continued research and vigilant public health measures remain essential in managing the impact of this virus and preventing future outbreaks.

Source: https://www.sciencedaily.com/releases/2025/02/250212134940.htm