Drug Resistance Mutations Emerging in SARS-CoV-2 After Ensitrelvir Use in Japan to Treat COVID-19
Nikhil Prasad Fact checked by:Thailand Medical News Team Feb 18, 2025 2 days, 16 hours, 20 minutes ago
Medical News: Researchers Warn of Rising Drug Resistance Mutations in COVID 19 Treatment
A new study has raised concerns about emerging drug resistance mutations in patients treated with ensitrelvir, an antiviral drug used to combat COVID-19. Researchers from Kansai Medical University General Medical Center in Osaka and Hokkaido University in Sapporo have identified significant genetic changes in the virus that may reduce the drug’s effectiveness.
Drug Resistance Mutations Emerging in SARS-CoV-2 After Ensitrelvir Use in Japan to Treat COVID-19
Ensitrelvir (Xocova), a 3C-like protease inhibitor, was introduced under emergency regulatory approval in Japan in late 2022. It has since been widely used for COVID-19 treatment, particularly in cases where patients either failed to respond to other antiviral drugs or were at risk of severe illness. However, this
Medical News report highlights that certain mutations, such as M49L, are emerging in patients undergoing treatment, potentially reducing the drug’s efficacy.
The Study’s Findings on Drug Resistance Mutations
The researchers conducted genomic analysis on samples from hospitalized COVID-19 patients, focusing on the presence of mutations in the NSP5 region of the virus, which is associated with resistance to protease inhibitors like ensitrelvir. The study revealed several key findings:
-M49L Mutation Identified: Among patients treated with ensitrelvir, the M49L mutation was observed in a significant number of cases. This mutation is believed to confer resistance to the drug, making treatment less effective.
-Other Mutations Found: In addition to M49L, other resistance-associated mutations such as M49I, T25A, and S144A were detected in some patients.
-Viral Load Rebound: In patients who developed these mutations, a concerning trend of viral rebound was noted, meaning that after initial treatment, the virus began multiplying again.
-Community Spread of Resistant Strains: Some cases showed that M49L mutations were present in patients who had never received ensitrelvir, indicating that resistant strains may already be circulating in the general population.
How Quickly Do Resistance Mutations Appear
One of the most alarming aspects of the study was the speed at which these mutations developed. In some cases, the M49L mutation appeared as early as six days after starting treatment. This rapid evolution suggests that the barrier to resistance for ensitrelvir is lower than that of other antiviral drugs such as remdesivir and nirmatrelvir/ritonavir.
The study also found that M49L mutations tend to become dominant in infected individuals. Unlike some mutations that appear briefly and then fade, M49L is maintained in the virus population, indicating that it provides a survival advantage. This raises concerns about the long-ter
m effectiveness of ensitrelvir and the potential for widespread resistance.
Implications for COVID 19 Treatment
The findings suggest that ensitrelvir should be used with caution, especially in immunocompromised individuals who are more likely to develop persistent infections. The emergence of drug resistance mutations could reduce the effectiveness of treatment options and lead to prolonged illness or increased transmission of resistant strains.
Doctors and health officials must closely monitor patients receiving ensitrelvir to detect resistance mutations early. Alternative treatment strategies, such as using combination antiviral therapy or switching to different medications if resistance is suspected, may be necessary to prevent treatment failures.
Ensuring Effective Treatment for the Future
As the world continues to fight COVID-19, drug resistance remains a major challenge. This study highlights the need for ongoing surveillance of viral mutations and the development of new antiviral strategies to stay ahead of the virus. Researchers emphasize that further studies are needed to fully understand the implications of these mutations and to determine whether modifications to ensitrelvir or alternative drugs are needed to combat emerging resistance.
Conclusion
The study provides crucial insights into the risks associated with ensitrelvir treatment. It reveals that drug resistance mutations, particularly M49L, are developing rapidly in patients and may be spreading in the community. Given that ensitrelvir has a lower resistance barrier compared to other antiviral drugs, careful monitoring is essential. The rapid emergence of these mutations underscores the importance of continued genomic surveillance and the need to explore combination therapies or new drug formulations to prevent treatment failures.
The study findings were published in the peer-reviewed journal: Antiviral Research.
https://www.sciencedirect.com/science/article/pii/S0166354225000440
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