#C1208N 3CLPro T21I + E166V Expression Kit

3CL^pro (M^pro) T21I + E166V mutation Expression Kit

In a recombinant SARS-COV-2 assay conducted in huh7-ACE2 cells, the E166V mutation alone displayed a 100-fold IC50 resistance to nirmatrelvir, although it led to reduced fitness (Iketani et al. 2023). However, when combined with the T21I mutation, virus replication was restored (Iketani et al. 2023) resulting in an 83-fold change in nirmatrelvir resistance (Iketani et al. 2023). This T21I, E166V mutation has been identified in patients and reported to the GISAID database  (Shu and McCauley 2017; Iketani et al. 2023).  Pfizer also reported an 83-fold increase in EC₅₀ to nirmatrelvir using a biochemical assay (Pfizer Laboratories 2022).

• Identify protease inhibitors that maintain efficacy against the T21I + E166V mutation
• Easy co-expression with our 3CLglow and 3CLglowUp sensors
• Cost effective screening with minimal safety requirements (BSL-1)

Materials in the Kit:

• 3CL^pro T21I + E166V in BacMam
• Sodium Butyrate, 500 mM in H₂O

References:

Iketani, S., Mohri, H., Culbertson, B., Hong, S. J., Duan, Y., Luck, M. I., Annavajhala, M. K., Guo, Y., Sheng, Z., Uhlemann, A.-C., Goff, S. P., Sabo, Y., Yang, H., Chavez, A., & Ho, D. D. (2023). Multiple pathways for SARS-COV-2 resistance to Nirmatrelvir. Nature, 613(7944), 558–564. https://doi.org/10.1038/s41586-022-05514-2

Pfizer Laboratories. (2022). (rep.). FACT SHEET FOR HEALTHCARE PROVIDERS:  EMERGENCY USE AUTHORIZATION FOR PAXLOVID. Retrieved from https://labeling.pfizer.com/ShowLabeling.aspx?id=16474.

Shu, Y., & McCauley, J. (2017). GISAID: Global initiative on sharing all influenza data – from vision to reality. Eurosurveillance, 22(13). https://doi.org/10.2807/1560-7917.es.2017.22.13.30494