The kinetics of nsp7-11 polyprotein processing and impact on complexation with nsp16 among human coronaviruses.

ABSTRACT: In coronavirus (CoV) infection, polyproteins (pp1a/pp1ab) are processed into non-structural proteins (nsps), which largely form the replication/transcription complex (RTC). The polyprotein processing and complex formation is critical and offers potential therapeutic targets. However, the interplay of polyprotein processing and RTC-assembly remains poorly understood. Here, we study two key aspects: The order of polyprotein processing by viral main protease M^pro and its influence on complex formation with the methyltransferase nsp16. Moreover, we establish an approach to determine rate constants k from cleavage sites in structured CoV polyprotein based on native mass spectrometry (MS). The high sensitivity and precision of our method allow quantification of multi-reaction kinetics

SUBMITTER: Schamoni-Kast K 

PROVIDER: S-EPMC12420816 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature