How changes in the coronavirus main enzyme could cause Paxlovid resistance
Comprehensive analysis of epistasis in drug resistance potential of Mpro from SARS-CoV-2
This project looks at how combinations of changes in the virus's main enzyme might let SARS‑CoV‑2 resist nirmatrelvir, the active drug in Paxlovid, which matters for people treated for COVID‑19.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Univ of Massachusetts Med Sch Worcester NIH-funded |
| Lab location | 1 site (Worcester, United States) |
| Project ID | NIH-11270643 on NIH RePORTER |
What this research studies
The team uses a safe lab test in yeast (not live virus) to measure how different mutations in the virus main protease affect its activity and how well nirmatrelvir blocks it. They will systematically combine mutations that weaken drug binding with mutations that restore enzyme function and record the effects. The results will be analyzed alongside protein structure information to understand why certain mutation combinations cause resistance. The overall aim is to predict mutation patterns that could undermine Paxlovid so clinicians and drug developers can respond.
Who could benefit from this research
Good fit: People who have had COVID‑19, especially those who received Paxlovid or whose viral sequences show changes in the virus protease, may find the results relevant for future testing or treatment options.
Not a fit: Individuals without current or prior SARS‑CoV‑2 infection or those not treated with protease inhibitors are unlikely to see direct benefit from this laboratory research.
Why it matters
Potential benefit: If successful, this work could help detect emerging resistance earlier and guide the design of next‑generation antivirals to keep treatments like Paxlovid effective.
How similar studies have performed: Previous laboratory screens have identified individual Mpro mutations that reduce nirmatrelvir binding, but a comprehensive map of how combinations of mutations interact is novel.
Where this research is happening
Worcester, United States
- Univ of Massachusetts Med Sch Worcester — Worcester, United States (Active)
Researchers
- Principal investigator: Bolon, Daniel N — Univ of Massachusetts Med Sch Worcester
- Study coordinator: Bolon, Daniel N
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.