ABSTRACT
Nirmatrelvir is a SARS-CoV-2 Mpro inhibitor in Paxlovid. Patients treated with it often produce mutant viruses in which the Mpro resists Nirmatrelvir inhibition. A common interpretation is that the mutations allow the virus to escape inhibition, but here we report that these mutations enable the protease to more effectively cleave the host protein NF-kappa-B essential modulator (NEMO), which weakens the immune response, improves viral replication, and may contribute to long COVID.
Competing Interest Statement
Thom Hughes and Merrilee Thomas work at Montana Molecular, where some of these tools are sold. We declare no competing interest.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted October 19, 2024.
Nirmatrelvir-Resistant Mutations in SARS-CoV-2 Mpro Enhance Host Immune Evasion via Cleavage of NF-κB Essential Modulator
