#C1204N 3CLPro Q189E Expression Kit

3CL^pro (M^pro) Q189E mutation Expression Kit

Q189E, located within 6 Å of the nirmatrelvir binding site, is a naturally occurring mutation and has a two-fold increase in enzymatic activity compared to wild type 3CLpro (Hu et al. 2023). In a biochemical assay, Q189E reported a 19-fold increase in IC50 to nirmatrelvir resistance (Sasi et al. 2022). Additionally, a FRET-based enzymatic assay revealed a 10.7-fold increase in IC50 of nirmatrelvir (Huang et al. 2023).

• Identify protease inhibitors that maintain efficacy against the Q189E 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 Q189E in BacMam
• Sodium Butyrate, 500 mM in H₂O

References:

Hu, Y., Lewandowski, E. M., Tan, H., Zhang, X., Morgan, R. T., Zhang, X., Jacobs, L. M., Butler, S. G., Gongora, M. V., Choy, J., Deng, X., Chen, Y., & Wang, J. (2023). Naturally occurring mutations of SARS-COV-2 main protease confer drug resistance to Nirmatrelvir. ACS Central Science, 9(8), 1658–1669. https://doi.org/10.1021/acscentsci.3c00538

Huang, C., Shuai, H., Qiao, J., Hou, Y., Zeng, R., Xia, A., Xie, L., Fang, Z., Li, Y., Yoon, C., Huang, Q., Hu, B., You, J., Quan, B., Zhao, X., Guo, N., Zhang, S., Ma, R., Zhang, J., … Yang, S. (2023). A new generation mpro inhibitor with potent activity against SARS-COV-2 omicron variants. Signal Transduction and Targeted Therapy, 8(1). https://doi.org/10.1038/s41392-023-01392-w

Sasi, V. M., Ullrich, S., Ton, J., Fry, S. E., Johansen-Leete, J., Payne, R. J., Nitsche, C., & Jackson, C. J. (2022). Predicting antiviral resistance mutations in SARS-COV-2 main protease with computational and experimental screening. Biochemistry, 61(22), 2495–2505. https://doi.org/10.1021/acs.biochem.2c00489