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Nirmatrelvir


Mechanism of action:

Nirmatrelvir is a SARS-CoV-2 3CL protease inhibitor. After SARS-CoV-2 enters the host cell, it first produces the polyprotein precursors pp1a and pp1ab. These precursors must be cleaved at different sites by PLpro and the 3CL protease to generate 16 functional nonstructural proteins involved in viral transcription and replication. Nirmatrelvir binds to the active site of 3CLpro and prevents polyprotein cleavage, thereby blocking viral transcription and replication.

Reference(s):

1. Ionescu MI et al. (2020). An Overview of the Crystallized Structures of the SARS-CoV-2. Protein J. 


2. Muramatsu T et al. (2016). SARS-CoV 3CL protease cleaves its C-terminal autoprocessing site by novel subsite cooperativity. Proc Natl Acad Sci U S A. 


3. Xiong M et al. (2021). What coronavirus 3C-like protease tells us: From structure, substrate selectivity, to inhibitor design. Med Res Rev.

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