20220318 Liang PH Epub

SARS-CoV-2 3CLpro displays faster self-maturation in vitro than SARS-CoV 3CLpro due to faster C-terminal cleavage

SARS-CoV-2 3CL<sup>pro</sup> displays faster self-maturation in vitro than SARS-CoV 3CL<sup>pro</sup> due to faster C-terminal cleavage

FEBS Lett. 2022 May 16; 596(9):1214-1224. Epub 2022 Mar 28.
doi: 10.1002/1873-3468.14337

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Kuo CJ*, Liang PH*

摘要

The coronavirus (CoV) disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a worldwide pandemic. The 3C-like protease (3CLpro ), which cleaves 11 sites including its own N- and C-termini on the viral polyproteins, is essential for SARS-CoV-2 replication. In this study, we constructed the full-length inactive 3CLpro with N- and C-terminal extensions as substrates for monitoring self-cleavage by wild-type 3CLpro . We found that the rate-limiting C-terminal self-cleavage rate of SARS-CoV-2 3CLpro was 35-fold faster than that of SARS-CoV 3CLpro using the Trx/GST-tagged C145A 3CLpro substrates. Since self-cleavage of 3CLpro is the initial step for maturation of other viral proteins, our study suggests more facile SARS-CoV-2 replication than that of SARS-CoV.